CN1168633A - 硼酸酯和硼酸化合物,其合成和应用 - Google Patents
硼酸酯和硼酸化合物,其合成和应用 Download PDFInfo
- Publication number
- CN1168633A CN1168633A CN95196590A CN95196590A CN1168633A CN 1168633 A CN1168633 A CN 1168633A CN 95196590 A CN95196590 A CN 95196590A CN 95196590 A CN95196590 A CN 95196590A CN 1168633 A CN1168633 A CN 1168633A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- aryl
- aralkyl
- chemical compound
- independently
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 289
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 8
- 239000002253 acid Chemical class 0.000 title abstract description 16
- 150000002148 esters Chemical class 0.000 title abstract description 10
- 238000003786 synthesis reaction Methods 0.000 title abstract description 4
- 238000000034 method Methods 0.000 claims abstract description 76
- 241001465754 Metazoa Species 0.000 claims abstract description 37
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 24
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 20
- 230000015556 catabolic process Effects 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims description 192
- 125000000217 alkyl group Chemical group 0.000 claims description 164
- 125000000623 heterocyclic group Chemical group 0.000 claims description 137
- -1 N-morpholinyl Chemical group 0.000 claims description 120
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 117
- 229920006395 saturated elastomer Polymers 0.000 claims description 101
- 229910052739 hydrogen Inorganic materials 0.000 claims description 95
- 239000001257 hydrogen Substances 0.000 claims description 95
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 93
- 229960003136 leucine Drugs 0.000 claims description 93
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 88
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 84
- 239000004327 boric acid Substances 0.000 claims description 83
- 239000004395 L-leucine Substances 0.000 claims description 82
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 79
- 229940079156 Proteasome inhibitor Drugs 0.000 claims description 73
- 239000003207 proteasome inhibitor Substances 0.000 claims description 73
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 66
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 51
- 125000003545 alkoxy group Chemical group 0.000 claims description 48
- 108010057466 NF-kappa B Proteins 0.000 claims description 46
- 102000003945 NF-kappa B Human genes 0.000 claims description 46
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 125000004104 aryloxy group Chemical group 0.000 claims description 43
- 229910052799 carbon Inorganic materials 0.000 claims description 43
- 125000005842 heteroatom Chemical group 0.000 claims description 43
- 125000004429 atom Chemical group 0.000 claims description 41
- 125000004432 carbon atom Chemical group C* 0.000 claims description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 40
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 39
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 39
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 39
- 230000000694 effects Effects 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 32
- 230000017854 proteolysis Effects 0.000 claims description 30
- MOILFCKRQFQVFS-BDNRQGISSA-N (1r,3s,4r,5r)-4,6,6-trimethylbicyclo[3.1.1]heptane-3,4-diol Chemical compound C1[C@@H]2C(C)(C)[C@H]1C[C@H](O)[C@@]2(O)C MOILFCKRQFQVFS-BDNRQGISSA-N 0.000 claims description 28
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- 125000004122 cyclic group Chemical group 0.000 claims description 25
- PFURGBBHAOXLIO-UHFFFAOYSA-N cyclohexane-1,2-diol Chemical compound OC1CCCCC1O PFURGBBHAOXLIO-UHFFFAOYSA-N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 22
- 125000006239 protecting group Chemical group 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 230000005764 inhibitory process Effects 0.000 claims description 19
- 125000000468 ketone group Chemical group 0.000 claims description 19
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 17
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 17
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 16
- 206010061218 Inflammation Diseases 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 230000004054 inflammatory process Effects 0.000 claims description 15
- UXFQFBNBSPQBJW-UHFFFAOYSA-N 2-amino-2-methylpropane-1,3-diol Chemical compound OCC(N)(C)CO UXFQFBNBSPQBJW-UHFFFAOYSA-N 0.000 claims description 14
- 102000004190 Enzymes Human genes 0.000 claims description 14
- 108090000790 Enzymes Proteins 0.000 claims description 14
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 14
- 229960003767 alanine Drugs 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 12
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 claims description 12
- 229910052798 chalcogen Inorganic materials 0.000 claims description 12
- 150000001787 chalcogens Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- 108050006400 Cyclin Proteins 0.000 claims description 10
- 102000016736 Cyclin Human genes 0.000 claims description 10
- 102000011195 Profilin Human genes 0.000 claims description 10
- 108050001408 Profilin Proteins 0.000 claims description 10
- 210000001519 tissue Anatomy 0.000 claims description 10
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 9
- 230000012010 growth Effects 0.000 claims description 9
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 9
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 8
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000005493 quinolyl group Chemical group 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- 208000023275 Autoimmune disease Diseases 0.000 claims description 7
- 102000008934 Muscle Proteins Human genes 0.000 claims description 7
- 108010074084 Muscle Proteins Proteins 0.000 claims description 7
- 230000030741 antigen processing and presentation Effects 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 7
- 230000001419 dependent effect Effects 0.000 claims description 7
- 230000002757 inflammatory effect Effects 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 230000003834 intracellular effect Effects 0.000 claims description 6
- 210000000056 organ Anatomy 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 206010048768 Dermatosis Diseases 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 230000001093 anti-cancer Effects 0.000 claims description 5
- 230000021164 cell adhesion Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 5
- 208000017520 skin disease Diseases 0.000 claims description 5
- KTHUKEZOIFYPEH-UHFFFAOYSA-N 1-benzylnaphthalene Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=CC=CC=C1 KTHUKEZOIFYPEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 4
- ZRKWMRDKSOPRRS-UHFFFAOYSA-N N-Methyl-N-nitrosourea Chemical compound O=NN(C)C(N)=O ZRKWMRDKSOPRRS-UHFFFAOYSA-N 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 125000001626 borono group Chemical group [H]OB([*])O[H] 0.000 claims description 2
- YFAHQZJLWAGGAG-JEDNCBNOSA-N (2s)-2-amino-4-methylpentanoic acid;boric acid Chemical compound OB(O)O.CC(C)C[C@H](N)C(O)=O YFAHQZJLWAGGAG-JEDNCBNOSA-N 0.000 claims 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
- 125000002648 azanetriyl group Chemical group *N(*)* 0.000 claims 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 description 98
- 210000004027 cell Anatomy 0.000 description 84
- 239000000243 solution Substances 0.000 description 82
- 239000000460 chlorine Substances 0.000 description 72
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 71
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
- 239000000047 product Substances 0.000 description 59
- 239000012317 TBTU Substances 0.000 description 58
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 53
- 235000010338 boric acid Nutrition 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- 239000000376 reactant Substances 0.000 description 44
- 206010028980 Neoplasm Diseases 0.000 description 42
- 239000007787 solid Substances 0.000 description 42
- 238000013459 approach Methods 0.000 description 40
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 37
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 37
- 239000012141 concentrate Substances 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000000284 extract Substances 0.000 description 32
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 31
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 31
- 201000011510 cancer Diseases 0.000 description 30
- 239000002585 base Substances 0.000 description 29
- 238000003756 stirring Methods 0.000 description 29
- 239000003112 inhibitor Substances 0.000 description 26
- 238000000746 purification Methods 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000007864 aqueous solution Substances 0.000 description 23
- 238000005406 washing Methods 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 22
- 108090000765 processed proteins & peptides Proteins 0.000 description 21
- MOILFCKRQFQVFS-VUMZSGCYSA-N (3r,4s)-4,6,6-trimethylbicyclo[3.1.1]heptane-3,4-diol Chemical compound C1C2C(C)(C)C1C[C@@H](O)[C@]2(O)C MOILFCKRQFQVFS-VUMZSGCYSA-N 0.000 description 20
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 20
- 238000012545 processing Methods 0.000 description 20
- 206010039491 Sarcoma Diseases 0.000 description 19
- 230000006870 function Effects 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 17
- 238000000605 extraction Methods 0.000 description 16
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 16
- 230000004913 activation Effects 0.000 description 15
- 150000001413 amino acids Chemical class 0.000 description 15
- JNQPQEHGPXDQTA-UHFFFAOYSA-N boric acid;2,2,2-trifluoroacetic acid Chemical compound OB(O)O.OC(=O)C(F)(F)F JNQPQEHGPXDQTA-UHFFFAOYSA-N 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 238000010511 deprotection reaction Methods 0.000 description 15
- 230000008878 coupling Effects 0.000 description 14
- 238000010168 coupling process Methods 0.000 description 14
- 238000005859 coupling reaction Methods 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 13
- 210000003205 muscle Anatomy 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 229940024606 amino acid Drugs 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 11
- 150000001299 aldehydes Chemical class 0.000 description 11
- 238000001035 drying Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 102000044159 Ubiquitin Human genes 0.000 description 10
- 108090000848 Ubiquitin Proteins 0.000 description 10
- 238000010792 warming Methods 0.000 description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- 125000003047 N-acetyl group Chemical group 0.000 description 9
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 8
- 241000725303 Human immunodeficiency virus Species 0.000 description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 8
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 101000617805 Homo sapiens Staphylococcal nuclease domain-containing protein 1 Proteins 0.000 description 7
- 101000830894 Homo sapiens Targeting protein for Xklp2 Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 201000004681 Psoriasis Diseases 0.000 description 7
- 101000942603 Schizosaccharomyces pombe (strain 972 / ATCC 24843) Condensin complex subunit 3 Proteins 0.000 description 7
- 102100021996 Staphylococcal nuclease domain-containing protein 1 Human genes 0.000 description 7
- 101000963191 Xenopus laevis Maternal DNA replication licensing factor mcm3 Proteins 0.000 description 7
- 235000004279 alanine Nutrition 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 230000005855 radiation Effects 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 230000034512 ubiquitination Effects 0.000 description 7
- 238000010798 ubiquitination Methods 0.000 description 7
- 210000002700 urine Anatomy 0.000 description 7
- BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 6
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 108010021699 I-kappa B Proteins Proteins 0.000 description 6
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 102000035195 Peptidases Human genes 0.000 description 6
- 108091005804 Peptidases Proteins 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 6
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000004519 grease Substances 0.000 description 6
- 239000000833 heterodimer Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000028709 inflammatory response Effects 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 230000035479 physiological effects, processes and functions Effects 0.000 description 6
- XOKSLPVRUOBDEW-UHFFFAOYSA-N pinane of uncertain configuration Natural products CC1CCC2C(C)(C)C1C2 XOKSLPVRUOBDEW-UHFFFAOYSA-N 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 208000037803 restenosis Diseases 0.000 description 6
- 238000010025 steaming Methods 0.000 description 6
- 230000001133 acceleration Effects 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000000571 coke Substances 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 125000005956 isoquinolyl group Chemical group 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 208000037816 tissue injury Diseases 0.000 description 5
- 238000001291 vacuum drying Methods 0.000 description 5
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 4
- 208000010444 Acidosis Diseases 0.000 description 4
- 102000007469 Actins Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 230000005778 DNA damage Effects 0.000 description 4
- 231100000277 DNA damage Toxicity 0.000 description 4
- 102000008379 I-kappa B Proteins Human genes 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 206010028289 Muscle atrophy Diseases 0.000 description 4
- 206010037660 Pyrexia Diseases 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- MWKOOGAFELWOCD-FKBYEOEOSA-N [(1r)-3-methyl-1-[[(2s)-4-methyl-2-[[(2s)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoyl]amino]butyl]boronic acid Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 MWKOOGAFELWOCD-FKBYEOEOSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 210000000805 cytoplasm Anatomy 0.000 description 4
- 239000002254 cytotoxic agent Substances 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 210000003712 lysosome Anatomy 0.000 description 4
- 230000001868 lysosomic effect Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229960004452 methionine Drugs 0.000 description 4
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 229930006728 pinane Natural products 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 229960002429 proline Drugs 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 4
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 108010016626 Dipeptides Proteins 0.000 description 3
- 229910004373 HOAc Inorganic materials 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- 229930182821 L-proline Natural products 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- 241000872931 Myoporum sandwicense Species 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- USPFMEKVPDBMCG-LBPRGKRZSA-N N-benzyloxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 USPFMEKVPDBMCG-LBPRGKRZSA-N 0.000 description 3
- 208000028389 Nerve injury Diseases 0.000 description 3
- 102000015094 Paraproteins Human genes 0.000 description 3
- 108010064255 Paraproteins Proteins 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 230000007950 acidosis Effects 0.000 description 3
- 208000026545 acidosis disease Diseases 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 3
- 125000000707 boryl group Chemical group B* 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 230000000994 depressogenic effect Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 208000030172 endocrine system disease Diseases 0.000 description 3
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- XALVRJFEYQMFRV-DQEYMECFSA-N n-[(2s)-1-[[(1r)-1-(1,3,6,2-dioxazaborocan-2-yl)-3-methylbutyl]amino]-3-naphthalen-1-yl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound N([C@@H](CC=1C2=CC=CC=C2C=CC=1)C(=O)N[C@@H](CC(C)C)B1OCCNCCO1)C(=O)N1CCOCC1 XALVRJFEYQMFRV-DQEYMECFSA-N 0.000 description 3
- 230000008764 nerve damage Effects 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 235000019419 proteases Nutrition 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000011435 rock Substances 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- 210000002027 skeletal muscle Anatomy 0.000 description 3
- 201000000849 skin cancer Diseases 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- ZAVSPTOJKOFMTA-SFHVURJKSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-phenylmethoxyphenyl)propanoic acid Chemical compound C1=CC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CC=C1OCC1=CC=CC=C1 ZAVSPTOJKOFMTA-SFHVURJKSA-N 0.000 description 2
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 2
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 2
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 2
- MHPUGCYGQWGLJL-UHFFFAOYSA-N 5-methyl-hexanoic acid Chemical compound CC(C)CCCC(O)=O MHPUGCYGQWGLJL-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 102100034613 Annexin A2 Human genes 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical group OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 2
- 208000035126 Facies Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102000003505 Myosin Human genes 0.000 description 2
- 108060008487 Myosin Proteins 0.000 description 2
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 101150070524 Rel gene Proteins 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 2
- 101710160666 Vascular cell adhesion protein 1 Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 125000005619 boric acid group Chemical class 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 102000008395 cell adhesion mediator activity proteins Human genes 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- 238000010668 complexation reaction Methods 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000002337 electrophoretic mobility shift assay Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 2
- 239000004226 guanylic acid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000008240 homogeneous mixture Substances 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 150000002440 hydroxy compounds Chemical class 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 108091006086 inhibitor proteins Proteins 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- NMPUCBGNQHTSRO-VXKWHMMOSA-N methyl-[(1r)-3-methyl-1-[[(2s)-2-(morpholine-4-carbonylamino)-3-naphthalen-1-ylpropanoyl]amino]butyl]borinic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2C=CC=1)C(=O)N[C@@H](CC(C)C)B(O)C)C(=O)N1CCOCC1 NMPUCBGNQHTSRO-VXKWHMMOSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 210000001087 myotubule Anatomy 0.000 description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- QRECHWNLQXPCIS-GOTSBHOMSA-N n-[(2s)-1-[[(1r)-1-dimethylboranyl-3-methylbutyl]amino]-3-naphthalen-1-yl-1-oxopropan-2-yl]morpholine-4-carboxamide Chemical compound N([C@@H](CC=1C2=CC=CC=C2C=CC=1)C(=O)N[C@@H](CC(C)C)B(C)C)C(=O)N1CCOCC1 QRECHWNLQXPCIS-GOTSBHOMSA-N 0.000 description 2
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000037311 normal skin Effects 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 2
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 2
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 2
- GJSGGHOYGKMUPT-UHFFFAOYSA-N phenoxathiine Chemical compound C1=CC=C2OC3=CC=CC=C3SC2=C1 GJSGGHOYGKMUPT-UHFFFAOYSA-N 0.000 description 2
- 230000007096 poisonous effect Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 150000003214 pyranose derivatives Chemical class 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 108700021653 rel Genes Proteins 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 201000008261 skin carcinoma Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical group C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 0.000 description 2
- PBLNHHSDYFYZNC-UHFFFAOYSA-N (1-naphthyl)methanol Chemical compound C1=CC=C2C(CO)=CC=CC2=C1 PBLNHHSDYFYZNC-UHFFFAOYSA-N 0.000 description 1
- AYIYVEPNEPUJCF-GNXRPPCSSA-N (1e,6e)-1,7-bis(3,4-dimethoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methylidene]hepta-1,6-diene-3,5-dione Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)C(C(=O)\C=C\C=1C=C(OC)C(OC)=CC=1)=CC1=CC=C(O)C(OC)=C1 AYIYVEPNEPUJCF-GNXRPPCSSA-N 0.000 description 1
- LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
- VDEMEKSASUGYHM-AXDSSHIGSA-N (2s)-3-phenylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1NCCC1C1=CC=CC=C1 VDEMEKSASUGYHM-AXDSSHIGSA-N 0.000 description 1
- TVXSGOBGRXNJLM-ZDUSSCGKSA-N (2s)-4-methyl-2-[methyl(phenylmethoxycarbonyl)amino]pentanoic acid Chemical compound CC(C)C[C@@H](C(O)=O)N(C)C(=O)OCC1=CC=CC=C1 TVXSGOBGRXNJLM-ZDUSSCGKSA-N 0.000 description 1
- BNEDIWBTOOXUFM-VXKWHMMOSA-N (2s)-n-[(1r)-1-(1,3,6,2-dioxazaborocan-2-yl)-3-methylbutyl]-2-(methanesulfonamido)-3-naphthalen-1-ylpropanamide Chemical compound B1([C@@H](NC(=O)[C@H](CC=2C3=CC=CC=C3C=CC=2)NS(C)(=O)=O)CC(C)C)OCCNCCO1 BNEDIWBTOOXUFM-VXKWHMMOSA-N 0.000 description 1
- NNZKQXXRWLSGLO-YFKPBYRVSA-N (5S)-5-propan-2-yl-2H-1,3-oxazol-2-id-4-one Chemical compound C(C)(C)[C@H]1C(N=[C-]O1)=O NNZKQXXRWLSGLO-YFKPBYRVSA-N 0.000 description 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- PHRABVHYUHIYGY-UHFFFAOYSA-N 1-methylnaphthalene Chemical group C1=CC=C2C([CH2])=CC=CC2=C1 PHRABVHYUHIYGY-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical group C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- 125000005955 1H-indazolyl group Chemical group 0.000 description 1
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 description 1
- DDEAEWMDOSXKBX-UHFFFAOYSA-N 2-(chloromethyl)quinoline Chemical compound C1=CC=CC2=NC(CCl)=CC=C21 DDEAEWMDOSXKBX-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- YNWRKPAPVXQHRE-UHFFFAOYSA-N 2-amino-3-hydroxy-5-naphthalen-1-ylpentanoic acid Chemical compound NC(C(=O)O)C(CCC1=CC=CC2=CC=CC=C12)O YNWRKPAPVXQHRE-UHFFFAOYSA-N 0.000 description 1
- GVUXWMQJDJQMLK-UHFFFAOYSA-N 2-azaniumyl-3-quinolin-6-ylpropanoate Chemical compound N1=CC=CC2=CC(CC(N)C(O)=O)=CC=C21 GVUXWMQJDJQMLK-UHFFFAOYSA-N 0.000 description 1
- WIKVRBTVPSOQHJ-UHFFFAOYSA-N 2h-1,5,2-dithiazine Chemical compound C1SNC=CS1 WIKVRBTVPSOQHJ-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- PRLKVVMRQFFIOQ-UHFFFAOYSA-N 3-naphthalen-1-ylpropanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CC=CC2=C1 PRLKVVMRQFFIOQ-UHFFFAOYSA-N 0.000 description 1
- YVZVRDDPHGQMQD-UHFFFAOYSA-N 3-naphthalen-1-ylpropanoyl chloride Chemical compound C1=CC=C2C(CCC(=O)Cl)=CC=CC2=C1 YVZVRDDPHGQMQD-UHFFFAOYSA-N 0.000 description 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 description 1
- WRFYIYOXJWKONR-UHFFFAOYSA-N 4-bromo-2-methoxyaniline Chemical compound COC1=CC(Br)=CC=C1N WRFYIYOXJWKONR-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- BMZKZBWPMWEQAY-UHFFFAOYSA-N 6h-1,2,5-thiadiazine Chemical compound C1SN=CC=N1 BMZKZBWPMWEQAY-UHFFFAOYSA-N 0.000 description 1
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 1
- 241000349731 Afzelia bipindensis Species 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 206010003594 Ataxia telangiectasia Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000013165 Bowen disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- JTJGANYYCBVFJC-OAHLLOKOSA-N C(=O)=C[C@@](C(=O)O)(C1=CC=CC2=CC=CC=C12)C Chemical compound C(=O)=C[C@@](C(=O)O)(C1=CC=CC2=CC=CC=C12)C JTJGANYYCBVFJC-OAHLLOKOSA-N 0.000 description 1
- CZUKPTBEGTVTJD-UHFFFAOYSA-N C1(CC(=O)OCCN(CCO1)C(C)=O)=O Chemical compound C1(CC(=O)OCCN(CCO1)C(C)=O)=O CZUKPTBEGTVTJD-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical group [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 108090000617 Cathepsin G Proteins 0.000 description 1
- 102000004173 Cathepsin G Human genes 0.000 description 1
- 102100024539 Chymase Human genes 0.000 description 1
- 108090000227 Chymases Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000009331 Homeodomain Proteins Human genes 0.000 description 1
- 108010048671 Homeodomain Proteins Proteins 0.000 description 1
- 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010053574 Immunoblastic lymphoma Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010027417 Metabolic acidosis Diseases 0.000 description 1
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 102100033174 Neutrophil elastase Human genes 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- KAFHLONDOVSENM-HNNXBMFYSA-N O-Benzyl-L-tyrosine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1OCC1=CC=CC=C1 KAFHLONDOVSENM-HNNXBMFYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000139306 Platt Species 0.000 description 1
- 208000008939 Pneumonic Pasteurellosis Diseases 0.000 description 1
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 208000026214 Skeletal muscle atrophy Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 108010056079 Subtilisins Proteins 0.000 description 1
- 102000005158 Subtilisins Human genes 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- AXMVYSVVTMKQSL-UHFFFAOYSA-N UNPD142122 Natural products OC1=CC=C(C=CC=O)C=C1O AXMVYSVVTMKQSL-UHFFFAOYSA-N 0.000 description 1
- 238000003302 UV-light treatment Methods 0.000 description 1
- 235000009392 Vitis Nutrition 0.000 description 1
- 241000219095 Vitis Species 0.000 description 1
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000006336 acinar cell carcinoma Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000020990 adrenal cortex carcinoma Diseases 0.000 description 1
- 208000007128 adrenocortical carcinoma Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000002707 ameloblastic effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- XXRGLCKZBCIEKO-DLMDZQPMSA-N azocine Chemical compound C/1=C/C=C\N=C/C=C\1 XXRGLCKZBCIEKO-DLMDZQPMSA-N 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 150000007516 brønsted-lowry acids Chemical class 0.000 description 1
- 150000007528 brønsted-lowry bases Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- SCNIGJIBVSZFTG-UHFFFAOYSA-N carbonyl dichloride;morpholine Chemical compound ClC(Cl)=O.C1COCCN1 SCNIGJIBVSZFTG-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000015861 cell surface binding Effects 0.000 description 1
- JJLWDPACYBAGLR-SFTDATJTSA-N chembl484082 Chemical compound N([C@@H](CC=1C2=CC=CC=C2C=CC=1)C(=O)N[C@@H](CC(C)C)B)C(=O)N1CCOCC1 JJLWDPACYBAGLR-SFTDATJTSA-N 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940075419 choline hydroxide Drugs 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229940117916 cinnamic aldehyde Drugs 0.000 description 1
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- HUBANNPOLNYSAD-UHFFFAOYSA-N clopyralid Chemical compound OC(=O)C1=NC(Cl)=CC=C1Cl HUBANNPOLNYSAD-UHFFFAOYSA-N 0.000 description 1
- 239000011280 coal tar Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000000498 cooling water Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- ROBXZHNBBCHEIQ-BYPYZUCNSA-N ethyl (2s)-2-aminopropanoate Chemical compound CCOC(=O)[C@H](C)N ROBXZHNBBCHEIQ-BYPYZUCNSA-N 0.000 description 1
- YELGYVNOTOPSBM-UHFFFAOYSA-N ethyl 2-amino-3-quinolin-6-ylpropanoate Chemical compound N1=CC=CC2=CC(CC(N)C(=O)OCC)=CC=C21 YELGYVNOTOPSBM-UHFFFAOYSA-N 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- GGQOPZKTDHXXON-UHFFFAOYSA-N hexane;methanol Chemical compound OC.CCCCCC GGQOPZKTDHXXON-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 201000004933 in situ carcinoma Diseases 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical class C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- XAAKCCMYRKZRAK-UHFFFAOYSA-N isoquinoline-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=NC=CC2=C1 XAAKCCMYRKZRAK-UHFFFAOYSA-N 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000000966 lung oat cell carcinoma Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 238000005497 microtitration Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000001095 motoneuron effect Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- DYAIYQACHMAONU-PMACEKPBSA-N n-[(2s)-1-[[(1r)-1-dimethylboranyl-3-methylbutyl]amino]-1-oxo-4-phenylbutan-2-yl]morpholine-4-carboxamide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(C)C)NC(=O)N1CCOCC1)CC1=CC=CC=C1 DYAIYQACHMAONU-PMACEKPBSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004002 naphthaldehydes Chemical class 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 125000001151 peptidyl group Chemical group 0.000 description 1
- 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- AMMGCGVWJMRTQI-UHFFFAOYSA-N prop-1-en-2-yl carbonochloridate Chemical compound CC(=C)OC(Cl)=O AMMGCGVWJMRTQI-UHFFFAOYSA-N 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000003439 radiotherapeutic effect Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 201000006845 reticulosarcoma Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 230000025185 skeletal muscle atrophy Effects 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 239000002884 skin cream Substances 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 201000000270 spindle cell sarcoma Diseases 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- UVFAEQZFLBGVRM-MSMWPWNWSA-N succinyl-Leu-Leu-Val-Tyr-7-amino-4-methylcoumarin Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CCC(O)=O)CC(C)C)C(=O)NC=1C=C2OC(=O)C=C(C)C2=CC=1)C1=CC=C(O)C=C1 UVFAEQZFLBGVRM-MSMWPWNWSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- DTWNKTDZTLVHLG-RDJZCZTQSA-N tert-butyl (2s,3s)-3-hydroxy-2-naphthalen-1-yl-5-oxopyrrolidine-1-carboxylate Chemical compound O[C@H]1CC(=O)N(C(=O)OC(C)(C)C)[C@H]1C1=CC=CC2=CC=CC=C12 DTWNKTDZTLVHLG-RDJZCZTQSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
- 229960004441 tyrosine Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 150000003667 tyrosine derivatives Chemical class 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/26—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/04—Esters of boric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06043—Leu-amino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
Description
表I硼酸酯和硼酸化合物的合成 | |||
化合物 | 偶合试剂 | 硼酸脱保护a | N-末端保护 |
MG-261 | EDC | -- | -- |
MG-262 | EDC | A | -- |
MG-264 | BOP | -- | -- |
MG-267 | EDC | -- | -- |
MG-268 | EDC | A | NaH,MeI |
MG-270 | EDC | A | -- |
MG-272 | EDC | A | -- |
MG-273 | EDC | A,B | RC(O)Cl |
MG-274 | BOP | A | -- |
MG-278 | EDC | A | RC(O)Cl |
MG-282 | EDC | A | -- |
MG-283 | BOP | A | Ac2O |
MG-284 | -- | B | RC(O)Cl |
MG-285 | BOP | A | RC(O)Cl |
MG-286 | EDC | A,B | RC(O)Cl |
MG-287 | EDC | B | Ac2O |
MG-288 | EDC | A | RC(O)Cl |
MG-289 | EDC | B | RS(O)2Cl |
MG-290 | EDC | B | Ac2O |
MG-291 | EDC | B | RS(O)2Cl |
MG-292 | BOP | B | RC(O)Cl |
MG-293 | TBTU | B | RC(O)Cl |
MG-294 | EDC | B | -- |
MG-295 | BOP | B | RS(O)2Cl |
MG-296 | EDC | B | RS(O)2Cl |
MG-297 | EDC | B | RS(O)2Cl |
MG-298 | EDC | B | RC(O)Cl |
MG-299 | EDC | B | RC(O)Cl |
化合物 | 偶合试剂 | 硼酸脱保护a | N-末端保护 |
MG-300 | EDC | B | RC(O)Cl |
MG-301 | BOP | B | Ac2O |
MG-302 | EDC | B | -- |
MG-303 | EDC | B | HCl,乙醚 |
MG-304 | TBTU | B | -- |
MG-305 | EDC | B | RC(O)Cl |
MG-306 | TBTU | B | RC(O)Cl |
MG-307 | TBTU | B | RC(O)Cl |
MG-308 | TBTU | B | RC(O)Cl |
MG-309 | TBTU | B | RC(O)Cl |
MG-310 | BOP | B | Ac2O |
MG-311 | BOP | B | HCl,二噁烷 |
MG-312 | EDC | B | RC(O)Cl |
MG-313 | -- | B | RCO2H,TBTU |
MG-314 | TBTU | B | RC(O)Cl |
MG-315 | BOP | B | RC(O)Cl |
MG-316 | BOP | B | |
MG-319 | TBTU | B | |
MG-321 | TBTU | B | RC(O)Cl |
MG-322 | TBTU | B | RC(O)Cl |
MG-323 | -- | B | Ac2O |
MG-325 | TBTU | B | RCO2H,TBTU |
MG-328 | TBTU | B | RC(O)Cl |
MG-329 | TBTU | B | RC(O)Cl |
MG-332 | TBTU | B | NaH,MeI |
MG-333 | TBTU | B | NaH,MeI |
MG-334 | TBTU | B | NaH,MeI |
MG-336 | TBTU | B | RC(O)Cl |
MG-337 | TBTU | B | HCl,二噁烷 |
MG-338 | EDC | B | RC(O)Cl |
化合物 | 偶合试剂 | 硼酸脱保护a | N-末端保护 |
MG-339 | TBTU | B | HCl,二噁烷 |
MG-340 | TBTU | B | HCl,二噁烷 |
MG-341 | TBTU | B | RCO2H,TBTU |
MG-342 | -- | B | RNH2,TBTU |
MG-343 | TBTU | B | RCO2H,TBTU |
MG-344 | BOP | B | Ac2O |
MG-345 | EDC | B | RC(O)Cl |
MG-346 | EDC | B | RC(O)Cl |
MG-347 | EDC | B | RS(O)2Cl |
MG-348 | TBTU | B | HCl,二噁烷 |
MG-349 | TBTU | B | HCl,二噁烷 |
MG-350 | TBTU | B | PhCH2NCO |
MG-351 | EDC | B | -- |
MG-352 | TBTU | B | RCO2H,TBTU |
MG-353 | TBTU | B | RC(O)Cl |
MG-354 | BOP | B | RS(O)2Cl |
MG-356 | TBTU | B | -- |
MG-357 | TBTU | B | HCl,二噁烷 |
MG-358 | TBTU | B | RC(O)Cl |
MG-359 | TBTU | B | HCl,二噁烷 |
MG-361 | TBTU | B | RCO2H,TBTU |
MG-362 | -- | B | PhCH2NCO |
MG-363 | TBTU | B | HCl,二噁烷 |
MG-364 | -- | B | RCO2H,TBTU |
MG-366 | TBTU | B | HCl,二噁烷 |
MG-367 | -- | B | RC(O)Cl |
MG-368 | EDC | B | TBTU |
MG-369 | TBTU | B | HCl,二噁烷 |
MG-380 | TBTU | B | RS(O)2Cl |
MG-382 | TBTU | B | RCO2H,TBTU |
化合物 | 偶合试剂 | 硼酸脱保护a | N-末端保护 |
MG-383 | TBTU | B | RCO2H,TBTU |
MG-385 | TBTU | B | HCl,二噁烷 |
MG-386 | TBTU | B | HCl,二噁烷 |
MG-387 | TBTU | B | RC(O)Cl |
表II硼酸酯和硼酸化合物对20S蛋白酶体的抑制 | ||||||
P-AA1-AA2-AA3-B(Z1)(Z2)化合物PaAA1 | ||||||
AA2b | AA3c | Z1,Z2 | 20S | |||
Ki(nM) | MG-261 | Cbz | L-Leu | |||
L-Leu | L-Leu | 蒎烷二醇 | 0.032 | MG-262 | Cbz | L-Leu |
L-Leu | L-Leu | (OH)2 | 0.035 | MG-264 | Cbz | -- |
L-Leu | L-Leu | 蒎烷二醇 | 119.00 | MG-267 | Cbz | -- |
L-Nal | L-Leu | 蒎烷二醇 | 0.100 | MG-268 | Cbz(N-Me) | -- |
L-Leu | L-Leu | (OH)2 | 998.00 | MG-270 | Cbz | -- |
L-Nal | L-Leu | (OH)2 | 0.083 | MG-272 | Cbz | -- |
D-(2-Nal) | L-Leu | (OH)2 | 34.0 | MG-273 | Morph | -- |
L-Nal | L-Leu | (OH)2 | 0.18 | MG-274 | Cbz | -- |
L-Leu | L-Leu | (OH)2 | 3.0 | MG-278 | Morph | L-Leu |
L-Leu | L-Leu | (OH)2 | 0.14 | MG-282 | Cbz | -- |
化合物 | Pa | AA1 | AA2b | AA3c | Z1,Z2 | 20SK1(nM) |
MG-293 | Morph | -- | D-Nal | D-Leu | (OH)2 | 2,300 |
MG-294 | H | -- | L-(3-Pal) | L-Leu | (OH)2 | 152 |
MG-295 | Ms | -- | L-Trp | L-Leu | (OH)2 | 5.8 |
MG-296 | (8-Quin)-SO2 | -- | L-Nal | L-Leu | (OH)2 | 1.7 |
MG-297 | Ts | -- | L-Nal | L-Leu | (OH)2 | 0.17 |
MG-298 | (2-Quin)-C(O) | -- | L-Nal | L-Leu | (OH)2 | 0.075 |
MG-299 | (2-喹喔啉基)-C(O) | -- | L-Nal | L-Leu | (OH)2 | 0.14 |
MG-300 | Morph | -- | L-(3-Pal) | L-Leu | (OH)2 | 1.3 |
MG-301 | Ac | -- | L-Trp | L-Leu | (OH)2 | 1.3 |
MG-302 | H | -- | L-Nal | L-Leu | (OH)2 | 7.5 |
MG-303 | H·HCl | -- | L-Nal | L-Leu | (OH)2 | 3.9 |
MG-304 | Ac | L-Leu | L-Nal | L-Leu | (OH)2 | 0.022 |
MG-305 | Morph | -- | D-Nal | L-Leu | (OH)2 | 189 |
MG-306 | Morph | -- | L-Tyr-(O-苄基) | L-Leu | (OH)2 | 0.23 |
MG-307 | Morph | -- | L-Tyr | L-Leu | (OH)2 | 0.51 |
MG-308 | Morph | -- | L-(2-Nal) | L-Leu | (OH)2 | 0.72 |
MG-309 | Morph | -- | L-Phe | L-Leu | (OH)2 | 0.82 |
化合物 | P | AA1 | AA2 | AA3 | X | 20SKi(nM) |
MG-105 | Z | -- | L-Leu | L-Leu | CHO | 15,000 |
MG-274 | Z | -- | L-Leu | L-Leu | B(OH)2 | 3.0 |
化合物 | 20SKi(nM) | 人白细胞弹性蛋白酶Ki(nM) | 组织蛋白酶GKi(nM) | 人胰凝乳蛋白酶Ki(nM) |
MG-262 | 0.03 | 15 | 55 | 7 |
MG-267 | 0.1 | 150 | 33,000 | 2,300 |
MG-296 | 1.7 | 36 | 9,200 | 75 |
MG-309 | 0.82 | 7,000 | 4,800 | 465 |
MG-341 | 0.6 | 2,300 | 628 | 322 |
P-AA1-AA2-AA3-B(Z1)(Z2) | ||||||
化合物 | Pa | AA1 | AA2b | AA3c | Z1,Z2 | IC50(nM) |
MG-262 | Cbz | L-Leu | L-Leu | L-Leu | (OH)2 | 280 |
MG-270 | Cbz | -- | L-Nal | L-Leu | (OH)2 | 730 |
MG-272 | Cbz | -- | D-(2-Nal) | L-Leu | (OH)2 | 6,000 |
MG-273 | Morph | -- | L-Nal | L-Leu | (OH)2 | 140 |
MG-274 | Cbz | -- | L-Leu | L-Leu | (OH)2 | 340 |
MG-278 | Morph | L-Leu | L-Leu | L-Leu | (OH)2 | 7,500 |
MG-282 | Cbz | -- | L-His | L-Leu | (OH)2 | 64,000 |
MG-283 | Ac | L-Leu | L-Leu | L-Leu | (OH)2 | 3,000 |
MG-285 | Morph | -- | L-Trp | L-Leu | (OH)2 | 2,400 |
MG-286 | Morph | -- | L-Nal | L-Leu | 二乙醇胺 | 95 |
MG-287 | Ac | -- | L-Nal | L-Leu | (OH)2 | 106 |
MG-289 | Ms | -- | L-(3-Pal) | L-Leu | (OH)2 | 10,830 |
MG-290 | Ac | -- | L-(3-Pal) | L-Leu | (OH)2 | 10,240 |
化合物 | 剂量(mg/kg) | %抑制 |
MG-296 | 50 | 60 |
MG-309 | 3 | 40 |
MG-341 | 3 | 90 |
Claims (89)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US33052594A | 1994-10-28 | 1994-10-28 | |
US08/330,525 | 1994-10-28 | ||
US08/442,581 US6083903A (en) | 1994-10-28 | 1995-05-16 | Boronic ester and acid compounds, synthesis and uses |
US08/442,581 | 1995-05-16 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2007100887250A Division CN101077875B (zh) | 1994-10-28 | 1995-10-27 | 硼酸酯和硼酸化合物,其合成和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1168633A true CN1168633A (zh) | 1997-12-24 |
CN1305475C CN1305475C (zh) | 2007-03-21 |
Family
ID=26987313
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB951965905A Expired - Lifetime CN1305475C (zh) | 1994-10-28 | 1995-10-27 | 硼酸酯和硼酸化合物,其合成和应用 |
CN2007100887250A Expired - Lifetime CN101077875B (zh) | 1994-10-28 | 1995-10-27 | 硼酸酯和硼酸化合物,其合成和应用 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2007100887250A Expired - Lifetime CN101077875B (zh) | 1994-10-28 | 1995-10-27 | 硼酸酯和硼酸化合物,其合成和应用 |
Country Status (25)
Country | Link |
---|---|
US (16) | US6083903A (zh) |
EP (4) | EP1312609B1 (zh) |
JP (1) | JP3717934B2 (zh) |
KR (1) | KR100398944B1 (zh) |
CN (2) | CN1305475C (zh) |
AT (3) | ATE314378T1 (zh) |
AU (1) | AU710564B2 (zh) |
CA (2) | CA2496538C (zh) |
CH (1) | CH0788360H1 (zh) |
CY (1) | CY2484B1 (zh) |
DE (5) | DE122004000025I1 (zh) |
DK (3) | DK1627880T3 (zh) |
ES (3) | ES2254803T3 (zh) |
FI (2) | FI114801B (zh) |
FR (1) | FR04C0014I2 (zh) |
HK (2) | HK1002059A1 (zh) |
IL (5) | IL133831A (zh) |
LU (1) | LU91083I2 (zh) |
MX (1) | MX9703063A (zh) |
NL (1) | NL300151I2 (zh) |
NO (2) | NO310558B1 (zh) |
NZ (2) | NZ337211A (zh) |
PT (3) | PT1312609E (zh) |
TW (1) | TW318850B (zh) |
WO (1) | WO1996013266A1 (zh) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101747354A (zh) * | 2008-12-04 | 2010-06-23 | 江苏先声药物研究有限公司 | 一类β氨基酸组成的二肽硼酸及其酯类化合物、制备方法及其用途 |
CN103450241A (zh) * | 2008-06-17 | 2013-12-18 | 米伦纽姆医药公司 | 硼酸酯化合物及其医药组合物 |
CN101638414B (zh) * | 2008-07-30 | 2014-01-08 | 江苏先声药物研究有限公司 | 肽硼酸及其酯类化合物、制备方法及其用途 |
CN103554143A (zh) * | 2008-09-29 | 2014-02-05 | 米伦纽姆医药公司 | 1-氨基-2-环丁基乙基硼酸衍生物 |
CN104822688A (zh) * | 2012-09-11 | 2015-08-05 | 西普拉有限公司 | 制备硼替佐米的方法 |
CN106478700A (zh) * | 2015-08-26 | 2017-03-08 | 杭州雷索药业有限公司 | 硼基取代的苯胺类蛋白激酶抑制剂 |
WO2017063491A1 (zh) * | 2015-10-15 | 2017-04-20 | 北京大学 | 脲拟肽硼酸化合物及其药物组合物、制备方法和用途 |
CN107474062A (zh) * | 2004-03-30 | 2017-12-15 | 千禧药品公司 | 硼的酯和酸化合物的合成 |
WO2022089556A1 (zh) * | 2020-10-30 | 2022-05-05 | 苏州开拓药业股份有限公司 | 一种c-Myc蛋白抑制剂及其制备方法和用途 |
Families Citing this family (293)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6083903A (en) * | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
US6838477B2 (en) * | 1995-04-12 | 2005-01-04 | President And Fellows Of Harvard College | Lactacystin analogs |
FR2758329B1 (fr) * | 1997-01-16 | 1999-02-12 | Synthelabo | Derives d'imidazole-4-butane boronique, leur preparation et leur utilisation en therapeutique |
US6271199B2 (en) * | 1997-02-15 | 2001-08-07 | Millennium Pharmaceuticals, Inc. | Treatment of infarcts |
US6221888B1 (en) * | 1997-05-29 | 2001-04-24 | Merck & Co., Inc. | Sulfonamides as cell adhesion inhibitors |
EP1017398A1 (en) * | 1997-09-25 | 2000-07-12 | Proscript, Inc. | Proteasome inhibitors, ubiquitin pathway inhibitors or agents that interfere with the activation of nf-kb via the ubiquitin proteasome pathway to treat inflammatory and autoimmune diseases |
CA2304206A1 (en) * | 1997-09-29 | 1999-04-08 | Point Therapeutics, Inc. | Stimulation of hematopoietic cells in vitro |
US6831057B2 (en) * | 1997-10-28 | 2004-12-14 | The University Of North Carolina At Chapel Hill | Use of NF-κB inhibition in combination therapy for cancer |
CA2219867A1 (en) * | 1997-10-31 | 1999-04-30 | Jiangping Wu | The use of proteasome inhibitors for treating cancer, inflammation, autoimmune disease, graft rejection and septic shock |
DE19802450A1 (de) * | 1998-01-23 | 1999-07-29 | Hoechst Marion Roussel De Gmbh | Ustilipide, Verfahren zu deren Herstellung sowie deren Verwendung |
US6075150A (en) * | 1998-01-26 | 2000-06-13 | Cv Therapeutics, Inc. | α-ketoamide inhibitors of 20S proteasome |
US6617171B2 (en) | 1998-02-27 | 2003-09-09 | The General Hospital Corporation | Methods for diagnosing and treating autoimmune disease |
FR2779653B1 (fr) * | 1998-06-11 | 2002-12-20 | Inst Nat Sante Rech Med | Utilisation de composes modulateurs du proteasome en therapie |
US6462019B1 (en) | 1998-07-10 | 2002-10-08 | Osteoscreen, Inc. | Inhibitors of proteasomal activity and production for stimulating bone growth |
US6902721B1 (en) | 1998-07-10 | 2005-06-07 | Osteoscreen, Inc. | Inhibitors of proteasomal activity for stimulating bone growth |
US6838436B1 (en) * | 1998-07-10 | 2005-01-04 | Osteoscreen Inc. | Inhibitors of proteasomal activity for stimulating bone growth |
US6979697B1 (en) * | 1998-08-21 | 2005-12-27 | Point Therapeutics, Inc. | Regulation of substrate activity |
EP0982317A1 (en) * | 1998-08-26 | 2000-03-01 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Bivalent inhibitors of the proteasome |
US6613541B1 (en) * | 1998-10-20 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Method for monitoring proteasome inhibitor drug action |
US6492333B1 (en) | 1999-04-09 | 2002-12-10 | Osteoscreen, Inc. | Treatment of myeloma bone disease with proteasomal and NF-κB activity inhibitors |
US6890904B1 (en) * | 1999-05-25 | 2005-05-10 | Point Therapeutics, Inc. | Anti-tumor agents |
US6649593B1 (en) * | 1999-10-13 | 2003-11-18 | Tularik Inc. | Modulators of SREBP processing |
WO2002014381A2 (en) * | 2000-08-16 | 2002-02-21 | University Of Alberta | Non-pressurized methods for the preparation of conjugated solid supports for boronic acids |
US6919382B2 (en) | 2000-08-31 | 2005-07-19 | The Governors Of The University Of Alberta | Preparation and uses of conjugated solid supports for boronic acids |
EP2301565A1 (de) * | 2000-10-12 | 2011-03-30 | ViroLogik GmbH | Verwendung von Proteasome Hemmern zur Behandlung von Virus-Infektionen |
ATE501157T1 (de) * | 2001-01-25 | 2011-03-15 | Us Of America Represented By The Secretary Dept Of Health And Human Services | Formulierungen von borsäure-verbindungen |
US7112588B2 (en) * | 2001-05-21 | 2006-09-26 | Alcon, Inc. | Use of proteasome inhibitors to treat dry eye disorders |
US6740674B2 (en) | 2001-05-21 | 2004-05-25 | Alcon, Inc. | Use of proteasome inhibitors to treat dry eye disorders |
DE60209227T2 (de) * | 2001-05-30 | 2006-08-17 | Novartis Ag | 2-((n-(2-amino-3-(heteroaryl- oder -aryl)propionyl)aminoacyl)amino)-alkylboronsäurederivate |
WO2003033506A1 (fr) * | 2001-10-12 | 2003-04-24 | Kyorin Pharmaceutical Co., Ltd. | Derive d'acide d'aminoborane et medicament inhibiteur de proteasomes le contenant |
WO2003033507A1 (fr) * | 2001-10-12 | 2003-04-24 | Kyorin Pharmaceutical Co., Ltd. | Derives d'acide benzylmalonique et inhibiteurs de proteasomes les contenant |
WO2003059898A2 (en) * | 2002-01-08 | 2003-07-24 | Eisai Co. Ltd. | Eponemycin and epoxomicin analogs and uses thereof |
EP1487459A4 (en) * | 2002-03-12 | 2006-05-24 | Ariad Pharma Inc | PEPTIDE ANALOGUES AND USES |
DK1485354T3 (da) | 2002-03-13 | 2008-09-01 | Janssen Pharmaceutica Nv | Sulfonylamino-derivater som nye inhibitorer af histandeacetylase |
US7592450B2 (en) * | 2002-03-13 | 2009-09-22 | Janssen Pharmaceutica N.V. | Piperazinyl-, piperidinyl- and morpholinyl-derivatives as inhibitors of histone deacetylase |
DK1485348T3 (da) * | 2002-03-13 | 2008-09-29 | Janssen Pharmaceutica Nv | Carbonylamino-derivater som nye inhibitorer af histandeacetylase |
JP4472353B2 (ja) | 2002-03-13 | 2010-06-02 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ヒストンデアセチラーゼの新規な阻害剤としてのアミノ誘導体 |
DE50313092D1 (de) * | 2002-04-05 | 2010-10-28 | Virologik Gmbh | Mittel zur behandlung von flaviviridae-infektionen |
WO2003106384A2 (en) * | 2002-06-01 | 2003-12-24 | Johns Hopkins University | Novel boronic chalcone derivatives and uses thereof |
EP1578434A2 (en) * | 2002-07-09 | 2005-09-28 | Point Therapeutics, Inc. | Methods and compositions relating to isoleucine boroproline compounds |
AU2003271747B2 (en) * | 2002-08-14 | 2008-09-11 | Janssen Pharmaceutica N.V. | Use of NF-kappa B inhibitors for the treatment of mastitis |
JP2006511593A (ja) * | 2002-09-09 | 2006-04-06 | トライジェン・リミテッド | ボロン酸塩および血栓症の治療におけるその使用 |
US20060084592A1 (en) * | 2002-09-09 | 2006-04-20 | Trigen Limited | Peptide boronic acid inhibitors |
US20050119226A1 (en) * | 2003-09-09 | 2005-06-02 | Trigen Limited | Methods for synthesizing organoboronic compounds and products thereof |
US7112572B2 (en) * | 2002-09-09 | 2006-09-26 | Trigen Limited | Multivalent metal salts of boronic acids |
US20050282757A1 (en) * | 2002-09-09 | 2005-12-22 | Trigen Limited | Peptide boronic acid compounds useful in anticoagulation |
US20050176651A1 (en) * | 2002-09-09 | 2005-08-11 | Trigen Limited | Peptide boronic acids useful in making salts thereof |
EP1542768A1 (en) * | 2002-09-20 | 2005-06-22 | Alcon, Inc. | Use of cytokine synthesis inhibitors for the treatment of dry eye disorders |
EP1581629B1 (en) | 2002-12-06 | 2015-04-01 | Millennium Pharmaceuticals, Inc. | Methods for the identification, assessment, and treatment of patients with proteasome inhibition therapy |
CN100341880C (zh) * | 2003-02-13 | 2007-10-10 | 上海仁虎制药股份有限公司 | 新型硼酸或硼酸酯类化合物、制备方法及在药学上的应用 |
WO2005007211A2 (en) * | 2003-07-03 | 2005-01-27 | Medtronic Vascular Inc. | Medical devices with proteasome inhibitors for the treatment of restenosis |
US7576206B2 (en) * | 2003-08-14 | 2009-08-18 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
US7223745B2 (en) * | 2003-08-14 | 2007-05-29 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
MXPA06005104A (es) | 2003-11-05 | 2007-01-25 | Palingen Inc | Citotoxicidad de celulas b aumentada en anticuerpos de enlace a cdim. |
US20060052390A1 (en) * | 2003-12-24 | 2006-03-09 | Scios, Inc. | Treatment of multiple myeloma by p38 MAP kinase and proteasome inhibition |
CA2558106A1 (en) * | 2004-02-23 | 2005-09-09 | Trustees Of Tufts College | Inhibitors of dipeptidylpeptidase iv for regulating glucose metabolism |
GB0405272D0 (en) * | 2004-03-09 | 2004-04-21 | Trigen Ltd | Compounds |
US7371875B2 (en) * | 2004-03-12 | 2008-05-13 | Miikana Therapeutics, Inc. | Cytotoxic agents and methods of use |
AU2016202747B2 (en) * | 2004-03-30 | 2017-11-23 | Millennium Pharmaceuticals, Inc. | Synthesis of boronic ester and acid compounds |
CN102174076A (zh) | 2004-04-15 | 2011-09-07 | 普罗特奥里克斯公司 | 用于抑制蛋白酶体酶的化合物 |
US8198270B2 (en) | 2004-04-15 | 2012-06-12 | Onyx Therapeutics, Inc. | Compounds for proteasome enzyme inhibition |
CA2565407A1 (en) | 2004-05-10 | 2005-11-24 | Proteolix, Inc. | Compounds for enzyme inhibition |
CA2571421A1 (en) | 2004-06-24 | 2006-01-05 | Nicholas Valiante | Compounds for immunopotentiation |
US7842707B2 (en) | 2004-07-23 | 2010-11-30 | Nuada, Llc | Peptidase inhibitors |
NZ552865A (en) | 2004-07-28 | 2009-09-25 | Janssen Pharmaceutica Nv | Substituted indolyl alkyl amino derivatives as novel inhibitors of histone deacetylase |
EP2100899A3 (en) | 2004-10-20 | 2009-09-30 | Proteolix, Inc. | Compounds for proteasome enzyme inhibition |
TW200618820A (en) * | 2004-11-05 | 2006-06-16 | Alza Corp | Liposome formulations of boronic acid compounds |
WO2006052641A2 (en) | 2004-11-05 | 2006-05-18 | Palingen, Inc. | Antibody induced cell membrane wounding |
US8017395B2 (en) | 2004-12-17 | 2011-09-13 | Lifescan, Inc. | Seeding cells on porous supports |
US20070098685A1 (en) * | 2005-01-19 | 2007-05-03 | Brand Stephen J | Methods and kits to treat chronic inflammatory immune diseases by administering a proteasome inhibitor and an interleukin 2 receptor agonist |
KR101346886B1 (ko) | 2005-01-21 | 2014-01-02 | 아스텍스 테라퓨틱스 리미티드 | 제약 화합물 |
CA2595749A1 (en) * | 2005-01-27 | 2006-08-03 | Research Development Foundation | Combination therapy with triterpenoid compounds and proteasome inhibitors |
US7468383B2 (en) * | 2005-02-11 | 2008-12-23 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
HUE040060T2 (hu) | 2005-02-16 | 2019-02-28 | Anacor Pharmaceuticals Inc | Halogén-szubsztituált boronftalidok fertõzések kezelésére |
WO2006099261A2 (en) * | 2005-03-11 | 2006-09-21 | The University Of North Carolina At Chapel Hill | Potent and specific immunoproteasome inhibitors |
KR20080007642A (ko) * | 2005-04-29 | 2008-01-22 | 코산 바이오사이언시즈, 인코포레이티드 | 프로테아좀 억제제와 함께 17-aag 또는 17-ag 또는 둘중 하나의 전구약물을 사용하여 다발성 골수종을 치료하는방법 |
AU2006248938B2 (en) | 2005-05-18 | 2011-09-29 | Janssen Pharmaceutica N.V. | Substituted aminopropenyl piperidine or morpholine derivatives as novel inhibitors of histone deacetylase |
AU2006202209B2 (en) * | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
ES2400916T3 (es) * | 2005-06-08 | 2013-04-15 | Janssen Biotech, Inc. | Una terapia celular para degeneración ocular |
US20090017006A1 (en) * | 2005-07-06 | 2009-01-15 | Biodevelops Pharma Entwicklung Gmbh | Use of a compound for enhancing the expression of membrane proteins on the cell surface |
US7531517B2 (en) | 2005-08-10 | 2009-05-12 | 4Sc Ag | Inhibitors of cancer cell, T-cell and keratinocyte proliferation |
EP1752467A1 (en) | 2005-08-10 | 2007-02-14 | 4Sc Ag | Inhibitors of cancer cell, t-cell and keratinocyte proliferation |
US20070059382A1 (en) * | 2005-09-09 | 2007-03-15 | Board Of Regents, Univ. And Comm. College System Of Nevada... | Medical treatment of breast cancer with boric acid materials |
NZ568068A (en) | 2005-11-09 | 2011-10-28 | Proteolix Inc | Compounds for enzyme inhibition |
US20090221488A1 (en) * | 2005-12-08 | 2009-09-03 | Wood Kenneth W | Certain Compositions and Methods of Treatment |
CN106008583A (zh) | 2005-12-30 | 2016-10-12 | 安纳考尔医药公司 | 含硼的小分子 |
ES2396986T3 (es) * | 2006-01-19 | 2013-03-01 | Janssen Pharmaceutica N.V. | Derivados de piridina y pirimidina como inhibidores de histona desacetilasa |
PL1981874T3 (pl) * | 2006-01-19 | 2009-10-30 | Janssen Pharmaceutica Nv | Pochodne aminofenylowe jako nowe inhibitory deacetylazy histonowej |
CA2631874C (en) * | 2006-01-19 | 2014-11-18 | Janssen Pharmaceutica N.V. | Pyridine and pyrimidine derivatives as inhibitors of histone deacetylase |
DK1981875T3 (da) * | 2006-01-19 | 2014-07-14 | Janssen Pharmaceutica Nv | Substituerede indolylalkylaminoderivater som inhibitorer af histondeacetylase |
JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
PE20070978A1 (es) * | 2006-02-14 | 2007-11-15 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks) |
US8168614B2 (en) | 2006-02-16 | 2012-05-01 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-inflammatory agents |
TW200808739A (en) * | 2006-04-06 | 2008-02-16 | Novartis Vaccines & Diagnostic | Quinazolines for PDK1 inhibition |
US8741643B2 (en) * | 2006-04-28 | 2014-06-03 | Lifescan, Inc. | Differentiation of pluripotent stem cells to definitive endoderm lineage |
DE102006026464A1 (de) | 2006-06-01 | 2007-12-06 | Virologik Gmbh Innovationszentrum Medizintechnik Und Pharma | Pharmazeutische Zusammensetzung zur Behandlung von Virusinfektionen und / oder Tumorerkrankungen durch Inhibition der Proteinfaltung und des Proteinabbaus |
WO2007143600A2 (en) * | 2006-06-05 | 2007-12-13 | Incyte Corporation | Sheddase inhibitors combined with cd30-binding immunotherapeutics for the treatment of cd30 positive diseases |
NZ573759A (en) | 2006-06-19 | 2012-03-30 | Proteolix Inc | Peptide epoxyketones for proteasome inhibition |
US20090312284A1 (en) * | 2006-09-15 | 2009-12-17 | Janine Arts | Histone deacetylase inhibitors with combined activity on class-i and class-iib histone deacetylases in combination with proteasome inhibitors |
AU2007296259A1 (en) * | 2006-09-15 | 2008-03-20 | Janssen Pharmaceutica Nv | Combinations of class-I specific histone deacetylase inhibitors with proteasome inhibitors |
WO2008044045A1 (en) | 2006-10-12 | 2008-04-17 | Astex Therapeutics Limited | Pharmaceutical combinations |
US8916552B2 (en) | 2006-10-12 | 2014-12-23 | Astex Therapeutics Limited | Pharmaceutical combinations |
CA2606634A1 (en) * | 2006-12-08 | 2008-06-08 | Centenary Institute Of Cancer Medicine And Cell Biology | Assay for response to proteasome inhibitors |
JO3396B1 (ar) | 2007-06-20 | 2019-10-20 | Anacor Pharmaceuticals Inc | جزيئات صغيرة تحتوي على البورون |
US9080145B2 (en) | 2007-07-01 | 2015-07-14 | Lifescan Corporation | Single pluripotent stem cell culture |
CA2695225C (en) | 2007-07-31 | 2021-06-01 | Lifescan, Inc. | Differentiation of human embryonic stem cells to pancreatic endocrine |
GB0715087D0 (en) | 2007-08-03 | 2007-09-12 | Summit Corp Plc | Drug combinations for the treatment of duchenne muscular dystrophy |
TW200911237A (en) | 2007-08-03 | 2009-03-16 | Summit Corp Plc | Drug combinations for the treatment of duchenne muscular dystrophy |
DK2178888T3 (da) | 2007-08-06 | 2012-10-01 | Millennium Pharm Inc | Proteasomhæmmere |
US7442830B1 (en) * | 2007-08-06 | 2008-10-28 | Millenium Pharmaceuticals, Inc. | Proteasome inhibitors |
EA034601B1 (ru) * | 2007-08-06 | 2020-02-25 | Милленниум Фармасьютикалз, Инк. | Способ получения бороновых кислот |
AU2016253697A1 (en) * | 2007-08-06 | 2016-11-24 | Millennium Pharmaceuticals, Inc. | Proteasome inhibitors |
WO2009036281A2 (en) * | 2007-09-12 | 2009-03-19 | Dr. Reddy's Laboratories Ltd. | Bortezomib and process for producing same |
US20090076031A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched bortezomib |
ES2578905T5 (es) | 2007-10-04 | 2020-03-18 | Onyx Therapeutics Inc | Inhibidores de proteasa epoxi cetona peptídicos cristalinos y la síntesis de ceto-epóxidos de aminoácidos |
US7838673B2 (en) * | 2007-10-16 | 2010-11-23 | Millennium Pharmaceuticals, Inc. | Proteasome inhibitors |
US20090110688A1 (en) * | 2007-10-24 | 2009-04-30 | Georg Fertig | Combination therapy of type ii anti-cd20 antibody with a proteasome inhibitor |
US9062290B2 (en) * | 2007-11-27 | 2015-06-23 | Lifescan, Inc. | Differentiation of human embryonic stem cells |
CN101220048B (zh) * | 2007-12-14 | 2012-08-15 | 江苏先声药物研究有限公司 | ZnCl2催化下的蒎烷二醇酯的制备方法 |
ES2437595T3 (es) | 2007-12-20 | 2014-01-13 | Novartis Ag | Derivados de tiazol usados como inhibidores de la PI 3 quinasa |
BR122017025207B1 (pt) | 2008-02-21 | 2021-03-16 | Centocor Ortho Biotech Inc | superfície que faz parte de um recipiente ou matriz destinada para uso em uma cultura de células ou análises, desprovida de uma camada de células alimentadoras e desprovida de uma camada adsorvente |
RU2547441C2 (ru) | 2008-03-06 | 2015-04-10 | Анакор Фармасьютикалз, Инк. | Борсодержащие малые молекулы в качестве противовоспалительных агентов |
EP2285384A4 (en) * | 2008-05-12 | 2012-04-25 | Anacor Pharmaceuticals Inc | BORN SMALL MOLECULES |
ES2697798T3 (es) | 2008-06-30 | 2019-01-28 | Janssen Biotech Inc | Diferenciación de células madre pluripotentes |
US20100028307A1 (en) * | 2008-07-31 | 2010-02-04 | O'neil John J | Pluripotent stem cell differentiation |
WO2010028005A1 (en) | 2008-09-04 | 2010-03-11 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
EP2348863A4 (en) * | 2008-09-04 | 2012-03-07 | Anacor Pharmaceuticals Inc | BORN SMALL MOLECULES |
US9493489B2 (en) * | 2008-10-15 | 2016-11-15 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-protozoal agents |
WO2010048298A1 (en) * | 2008-10-21 | 2010-04-29 | Proteolix, Inc. | Combination therapy with peptide epoxyketones |
CN107904201B (zh) | 2008-10-31 | 2021-11-16 | 詹森生物科技公司 | 人胚胎干细胞向胰腺内分泌谱系的分化 |
CN107435038B (zh) | 2008-10-31 | 2021-07-09 | 詹森生物科技公司 | 人胚胎干细胞向胰腺内分泌谱系的分化 |
KR101837080B1 (ko) | 2008-11-20 | 2018-03-09 | 얀센 바이오테크 인코포레이티드 | 마이크로-캐리어 상의 만능 줄기 세포 배양 |
BRPI0921996A2 (pt) * | 2008-11-20 | 2015-08-18 | Centocor Ortho Biotech Inc | Métodos e composições para cultura e ligação de células em substratos planos. |
US8461364B2 (en) * | 2008-12-17 | 2013-06-11 | Glaxosmithkline Llc | Polymorphs of (S)-3-aminomethyl-7-(3-hydroxy-propoxy)-3H-benzo[C][1,2]oxaborol-1-OL |
EP2379077A4 (en) * | 2009-01-09 | 2013-09-11 | Sun Pharma Advanced Res Co Ltd | PHARMACEUTICAL COMPOSITION |
WO2010096574A1 (en) | 2009-02-20 | 2010-08-26 | Lisanti Michael P | A method of diagnosis or prognosis of a neoplasm comprising determining the level of expression of a protein in stromal cells adjacent to the neoplasm |
WO2010105008A2 (en) | 2009-03-12 | 2010-09-16 | Genentech, Inc. | Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents for the treatment of hematopoietic malignancies |
AR075899A1 (es) | 2009-03-20 | 2011-05-04 | Onyx Therapeutics Inc | Tripeptidos epoxicetonas cristalinos inhibidores de proteasa |
WO2010106135A1 (en) | 2009-03-20 | 2010-09-23 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Combined use for the treatment of ovarian carcinoma |
US9605317B2 (en) | 2009-03-24 | 2017-03-28 | Janssen Pharmaceutica Nv | Biomarkers for assessing peripheral neuropathy response to cancer treatment |
WO2010114770A1 (en) * | 2009-03-30 | 2010-10-07 | Cerulean Pharma Inc. | Polymer-agent conjugates, particles, compositions, and related methods of use |
JP2012522055A (ja) * | 2009-03-30 | 2012-09-20 | セルリアン・ファーマ・インコーポレイテッド | ポリマー‐薬剤抱合体、粒子、組成物、および関連する使用方法 |
WO2010114768A1 (en) * | 2009-03-30 | 2010-10-07 | Cerulean Pharma Inc. | Polymer-epothilone conjugates, particles, compositions, and related methods of use |
AU2009347159B2 (en) * | 2009-05-27 | 2015-09-03 | Cephalon, Inc. | Combination therapy for the treatment of multiple myeloma |
EP2443128B1 (en) | 2009-06-19 | 2017-12-20 | LEK Pharmaceuticals d.d. | New synthetic route for the preparation of alpha-amino boronic esters |
CN101928329B (zh) * | 2009-06-19 | 2013-07-17 | 北京大学 | 三肽硼酸(酯)类化合物、其制备方法和应用 |
EP2280016A1 (en) | 2009-07-27 | 2011-02-02 | LEK Pharmaceuticals d.d. | New synthetic route for the preparation of alpha-amino boronic esters via substituted alk-1-ynes |
EP2270019A1 (en) | 2009-06-19 | 2011-01-05 | LEK Pharmaceuticals d.d. | New synthetic route for the preparation of alpha-amino boronic esters |
US8293753B2 (en) | 2009-07-02 | 2012-10-23 | Novartis Ag | Substituted 2-carboxamide cycloamino ureas |
DE102009027754A1 (de) | 2009-07-15 | 2011-05-05 | Schubert, Ulrich, Dr. | Verfahren zur Hemmung der Reifung von dendritischen Zellen |
JP5819826B2 (ja) | 2009-07-20 | 2015-11-24 | ヤンセン バイオテツク,インコーポレーテツド | ヒト胚性幹細胞の分化 |
EP2456862A4 (en) | 2009-07-20 | 2013-02-27 | Janssen Biotech Inc | DIFFERENTIATION OF HUMAN EMBRYONIC STEM CELLS |
WO2011011302A2 (en) * | 2009-07-20 | 2011-01-27 | Centocor Ortho Biotech Inc. | Differentiation of human embryonic stem cells |
WO2011017125A1 (en) * | 2009-07-28 | 2011-02-10 | Anacor Pharmaceuticals, Inc. | Trisubstituted boron-containing molecules |
WO2011019618A1 (en) * | 2009-08-14 | 2011-02-17 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
WO2011022502A1 (en) | 2009-08-18 | 2011-02-24 | Georgetown University | Boronic acid compositions and methods related to cancer |
WO2011022337A1 (en) * | 2009-08-19 | 2011-02-24 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
WO2011029802A1 (en) | 2009-09-08 | 2011-03-17 | F. Hoffmann-La Roche Ag | 4-substituted pyridin-3-yl-carboxamide compounds and methods of use |
WO2011037731A1 (en) * | 2009-09-25 | 2011-03-31 | Anacor Pharmaceuticals, Inc. | Boron containing small molecules |
EP2305285A1 (en) | 2009-09-29 | 2011-04-06 | Julius-Maximilians-Universität Würzburg | Means and methods for treating ischemic conditions |
PL2519231T3 (pl) | 2009-10-01 | 2017-09-29 | Janssen Pharmaceutica Nv | Inhibitory proteasomów do leczenia raka |
WO2011049971A1 (en) | 2009-10-20 | 2011-04-28 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
US20110212918A1 (en) * | 2009-11-11 | 2011-09-01 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
JP5919196B2 (ja) | 2009-11-13 | 2016-05-18 | オニキス セラピューティクス, インク.Onyx Therapeutics, Inc. | 転移抑制のためのペプチドエポキシケトンの使用 |
WO2011087822A1 (en) | 2009-12-22 | 2011-07-21 | Cephalon, Inc. | Proteasome inhibitors and processes for their preparation, purification and use |
KR101867369B1 (ko) | 2009-12-23 | 2018-06-14 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 분화 |
KR101923537B1 (ko) | 2009-12-23 | 2018-11-29 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 분화 |
US20110178287A1 (en) | 2010-01-19 | 2011-07-21 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutic delivery |
US8716478B2 (en) | 2010-01-27 | 2014-05-06 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
BR112012022060A2 (pt) * | 2010-03-01 | 2018-05-08 | Onyx Therapeutics Inc | composto para a inibição de imunoproteassoma |
JP6013196B2 (ja) * | 2010-03-01 | 2016-10-25 | ヤンセン バイオテツク,インコーポレーテツド | 多能性幹細胞から誘導した細胞を精製するための方法 |
NZ602392A (en) * | 2010-03-18 | 2014-03-28 | Innopharma Inc | Stable bortezomib formulations |
US8263578B2 (en) | 2010-03-18 | 2012-09-11 | Innopharma, Inc. | Stable bortezomib formulations |
AP2012006482A0 (en) | 2010-03-19 | 2012-10-31 | Anacor Pharmacueticals Inc | Boron-containing small molecules as anti-protozoalagent |
WO2011119920A2 (en) | 2010-03-25 | 2011-09-29 | Oregon Health & Science University | Cmv glycoproteins and recombinant vectors |
NZ602622A (en) * | 2010-03-31 | 2015-01-30 | Millennium Pharm Inc | Derivatives of 1-amino-2-cyclopropylethylboronic acid |
AU2013204868B2 (en) * | 2010-03-31 | 2016-10-13 | Millennium Pharmaceuticals, Inc. | Derivatives of 1-amino-2-cyclopropylethylboronic acid |
RU2012147246A (ru) | 2010-04-07 | 2014-05-20 | Оникс Терапьютикс, Инк. | Кристаллический пептидный эпоксикетонный ингебитор иммунопротеасомы |
CN101812026B (zh) * | 2010-04-12 | 2013-08-28 | 亚邦医药股份有限公司 | 一种硼替佐米的合成方法 |
CN102946879B (zh) | 2010-04-19 | 2015-04-22 | 尼基制药公司 | 一种蛋白酶体抑制剂和镓络合物在制备治疗增殖性疾病的药物中的应用 |
US8809282B2 (en) | 2010-05-06 | 2014-08-19 | Duke University | Method of reducing titers of antibodies specific for a therapeutic agent |
DK2569419T3 (da) | 2010-05-12 | 2019-05-13 | Janssen Biotech Inc | Differentiering af humane embryoniske stamceller |
EP2571525A4 (en) | 2010-05-18 | 2016-04-27 | Cerulean Pharma Inc | Compositions and methods for treating autoimmune and other diseases |
AR082418A1 (es) | 2010-08-02 | 2012-12-05 | Novartis Ag | Formas cristalinas de 1-(4-metil-5-[2-(2,2,2-trifluoro-1,1-dimetil-etil)-piridin-4-il]-tiazol-2-il)-amida de 2-amida del acido (s)-pirrolidin-1,2-dicarboxilico |
SG187947A1 (en) | 2010-08-31 | 2013-03-28 | Janssen Biotech Inc | Differentiation of pluripotent stem cells |
SG187946A1 (en) | 2010-08-31 | 2013-03-28 | Janssen Biotech Inc | Differentiation of human embryonic stem cells |
SG10201506852VA (en) | 2010-08-31 | 2015-10-29 | Janssen Biotech Inc | Differentiation of human embryonic stem cells |
US9126997B1 (en) | 2010-09-07 | 2015-09-08 | Northwestern University | Synergistic effect of glucocorticoid receptor agonists in combination with proteosome inhibitors for treating leukemia and myeloma |
ES2635333T3 (es) | 2010-09-07 | 2017-10-03 | Anacor Pharmaceuticals, Inc. | Derivados de benzoxaborol para tratar infecciones bacterianas |
AU2011312264B2 (en) | 2010-10-05 | 2015-07-02 | Fresenius Kabi Usa, Llc | Bortezomib formulations stabilised with boric acid |
EP2627636B1 (en) | 2010-10-14 | 2015-09-02 | Synthon BV | Process for making bortezomib and the intermediates for the process |
CN103476777B (zh) | 2011-01-31 | 2015-05-27 | 诺瓦提斯公司 | 新杂环衍生物 |
TW201309303A (zh) | 2011-03-03 | 2013-03-01 | Cephalon Inc | 用於治療狼瘡的蛋白酶體抑制劑 |
WO2012135528A2 (en) | 2011-03-29 | 2012-10-04 | Texas Tech University System | Galectin-3c combination therapy for human cancer |
BR112013025005A2 (pt) | 2011-03-31 | 2017-01-17 | Nanocarrier Co Ltd | composição farmacêutica contendo copolímero por blocos compreendendo composto de ácido borônico |
CA2832109C (en) | 2011-06-10 | 2021-07-06 | Oregon Health & Science University | Cmv glycoproteins and recombinant vectors |
WO2012177835A1 (en) * | 2011-06-22 | 2012-12-27 | Cephalon, Inc. | Proteasome inhibitors and processes for their preparation, purification and use |
US8481655B2 (en) | 2011-07-27 | 2013-07-09 | Wacker Chemical Corporation | Copper complexes of amino-functional organosilicon compounds and their use |
WO2013021032A1 (en) | 2011-08-11 | 2013-02-14 | Janssen Pharmaceutica Nv | Histone deacetylase inhibitors in combination with proteasome inhibitors and dexamethasone |
RS55053B1 (sr) | 2011-08-11 | 2016-12-30 | Janssen Pharmaceutica Nv | Prediktori za lečenje kancera |
EA032841B1 (ru) | 2011-08-19 | 2019-07-31 | Глаксо Груп Лимитед | Соединения для получения бензофуранового соединения для лечения инфекций, вызываемых вирусом гепатита с |
EP2753334B1 (en) | 2011-08-30 | 2022-10-19 | Trustees Of Tufts College | Fap-activated proteasome inhibitors for treating solid tumors |
CA2789539A1 (en) | 2011-09-12 | 2013-03-12 | International Aids Vaccine Initiative | Immunoselection of recombinant vesicular stomatitis virus expressing hiv-1 proteins by broadly neutralizing antibodies |
EP2586461A1 (en) | 2011-10-27 | 2013-05-01 | Christopher L. Parks | Viral particles derived from an enveloped virus |
WO2013061305A1 (en) | 2011-10-28 | 2013-05-02 | Novartis Ag | Novel purine derivatives and their use in the treatment of disease |
CN104080926B (zh) | 2011-10-28 | 2019-04-23 | 米伦纽姆医药公司 | 对nedd8活化酶(nae)抑制剂的反应的生物标记 |
JP6397765B2 (ja) | 2011-11-11 | 2018-09-26 | ミレニアム ファーマシューティカルズ, インコーポレイテッドMillennium Pharmaceuticals, Inc. | プロテアソーム阻害剤に応答するバイオマーカー |
CA2855368A1 (en) | 2011-11-11 | 2013-05-16 | Millennium Pharmaceuticals, Inc. | Biomarkers of response to proteasome inhibitors |
IN2014CN03580A (zh) | 2011-11-17 | 2015-10-09 | Univ Tokyo | |
KR102090751B1 (ko) | 2011-12-22 | 2020-03-19 | 얀센 바이오테크 인코포레이티드 | 인간 배아 줄기 세포의 단일 인슐린 호르몬 양성 세포로의 분화 |
US9732101B2 (en) | 2012-01-18 | 2017-08-15 | Wisconsin Alumni Research Foundation | Bioreversible boronates for delivery of molecules into cells |
US9234048B2 (en) | 2012-01-18 | 2016-01-12 | Wisconsin Alumni Research Foundation | Boronate-mediated delivery of molecules into cells |
JP6215235B2 (ja) | 2012-01-24 | 2017-10-18 | ミレニアム ファーマシューティカルズ, インコーポレイテッドMillennium Pharmaceuticals, Inc. | 癌の治療方法 |
WO2013112881A1 (en) | 2012-01-27 | 2013-08-01 | Thomas Jefferson University | Mct protein inhibitor-related prognostic and therapeutic methods |
US9409976B2 (en) | 2012-02-08 | 2016-08-09 | Igm Biosciences, Inc. | CDIM binding proteins and uses thereof |
EP2819673B1 (en) | 2012-03-02 | 2016-09-07 | Dr. Reddy's Laboratories Ltd. | Pharmaceutical compositions comprising boronic acid compounds |
SG11201405052RA (en) | 2012-03-07 | 2014-10-30 | Janssen Biotech Inc | Defined media for expansion and maintenance of pluripotent stem cells |
CA2784240C (en) | 2012-03-27 | 2014-07-08 | Innopharma, Inc. | Stable bortezomib formulations |
AU2013263043B2 (en) | 2012-05-16 | 2016-06-16 | Novartis Ag | Dosage regimen for a PI-3 kinase inhibitor |
CA2875786C (en) | 2012-06-08 | 2022-12-06 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells into pancreatic endocrine cells |
ES2631608T3 (es) | 2012-06-27 | 2017-09-01 | International Aids Vaccine Initiative | Variante de la glicoproteína Env del VIH-1 |
TW201414751A (zh) | 2012-07-09 | 2014-04-16 | 歐尼克斯治療公司 | 肽環氧酮蛋白酶抑制劑之前驅藥物 |
JP2013006855A (ja) * | 2012-09-03 | 2013-01-10 | Millennium Pharmaceuticals Inc | プロテアソーム阻害剤 |
US10662477B2 (en) | 2012-10-01 | 2020-05-26 | Millennium Pharmaceuticals, Inc. | Biomarkers and methods to predict response to inhibitors and uses thereof |
WO2014072985A1 (en) | 2012-11-06 | 2014-05-15 | Natco Pharma Limited | Novel boronic acid derivatives as anti cancer agents |
JP2015536342A (ja) | 2012-11-16 | 2015-12-21 | シルパ・メディケア・リミテッドShilpa Medicare Limited | 結晶ボルテゾミブの方法 |
WO2014097306A1 (en) | 2012-12-21 | 2014-06-26 | Natco Pharma Limited | Stable and pure polymorphic form of bortezomib |
WO2014105546A1 (en) | 2012-12-31 | 2014-07-03 | Janssen Biotech, Inc. | Differentiation of human embryonic stem cells into pancreatic endocrine cells using hb9 regulators |
BR112015015770A2 (pt) | 2012-12-31 | 2017-07-11 | Janssen Biotech Inc | cultivo de células-tronco embrionárias humanas na interface ar-líquido para diferenciação em células pancreáticas endócrinas |
US10370644B2 (en) | 2012-12-31 | 2019-08-06 | Janssen Biotech, Inc. | Method for making human pluripotent suspension cultures and cells derived therefrom |
WO2014106141A1 (en) | 2012-12-31 | 2014-07-03 | Janssen Biotech, Inc. | Suspension and clustering of human pluripotent cells for differentiation into pancreatic endocrine cells |
MX364895B (es) | 2013-03-13 | 2019-05-10 | Forma Therapeutics Inc | Nuevos compuestos y composiciones para la inhibicion de fasn. |
WO2014170628A1 (en) | 2013-04-16 | 2014-10-23 | Cipla Limited | Process for the preparation of bortezomib mannitol ester |
EP2986290A4 (en) | 2013-04-19 | 2017-01-04 | Thomas Jefferson University | Caveolin-1 related methods for treating glioblastoma with temozolomide |
US9603775B2 (en) | 2013-04-24 | 2017-03-28 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
WO2015003146A1 (en) | 2013-07-03 | 2015-01-08 | Georgetown University | Boronic acid derivatives of resveratrol for activating deacetylase enzymes |
US20150065381A1 (en) | 2013-09-05 | 2015-03-05 | International Aids Vaccine Initiative | Methods of identifying novel hiv-1 immunogens |
KR20160058886A (ko) | 2013-10-03 | 2016-05-25 | 밀레니엄 파머슈티컬스 인코퍼레이티드 | 전신 홍반성 낭창 및/또는 낭창성 신염의 예방 또는 치료 방법 |
EP2873423B1 (en) | 2013-10-07 | 2017-05-31 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
CN104586776B (zh) * | 2013-10-30 | 2017-05-17 | 扬子江药业集团上海海尼药业有限公司 | 以硼替佐米为活性成分的制剂及其制备方法 |
JP6468562B2 (ja) * | 2013-11-21 | 2019-02-13 | 国立大学法人北海道大学 | プロテアソーム阻害性化合物 |
WO2015085097A1 (en) * | 2013-12-05 | 2015-06-11 | The Broad Institute, Inc. | Compositions and methods for identifying and treating cachexia or pre-cachexia |
WO2015083101A1 (en) | 2013-12-06 | 2015-06-11 | Novartis Ag | Dosage regimen for an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor |
EP3102585B1 (en) | 2014-02-03 | 2021-05-19 | Ohio State Innovation Foundation | Boronic acid esters and pharmaceutical formulations thereof |
EP2910557A1 (en) * | 2014-02-20 | 2015-08-26 | Ikerchem, S.L. | Enantiopure tetrasubstituted pyrrolidines as scaffolds for proteasome inhibitors and medicinal applications thereof |
WO2015170757A1 (ja) | 2014-05-08 | 2015-11-12 | 国立大学法人 東京大学 | 医薬組成物 |
US10006006B2 (en) | 2014-05-16 | 2018-06-26 | Janssen Biotech, Inc. | Use of small molecules to enhance MAFA expression in pancreatic endocrine cells |
EA201692332A1 (ru) | 2014-05-20 | 2017-04-28 | Милленниум Фармасьютикалз, Инк. | Борсодержащие ингибиторы протеасом для применения после первичной противораковой терапии |
EP4180041A1 (en) | 2014-08-07 | 2023-05-17 | Mayo Foundation for Medical Education and Research | Compounds and methods for treating cancer |
RU2017115191A (ru) * | 2014-10-01 | 2018-11-06 | Мерк Патент Гмбх | Производные бороновой кислоты |
WO2016110870A1 (en) | 2015-01-07 | 2016-07-14 | Emcure Pharmaceuticals Limited | Pharmaceutical composition of bortezomid |
MA41505A (fr) | 2015-02-11 | 2017-12-19 | Millennium Pharm Inc | Nouvelle forme cristalline d'un inhibiteur de protéasome |
US20180243217A1 (en) | 2015-03-17 | 2018-08-30 | Leon-Nanodrugs Gmbh | Nanoparticles comprising a stabilized boronic acid compound |
US10174292B2 (en) | 2015-03-20 | 2019-01-08 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
EP3072901A1 (en) | 2015-03-23 | 2016-09-28 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
WO2016184793A1 (en) | 2015-05-15 | 2016-11-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for treating a patient with vegfr inhibitor-resistant metastatic renal cell carcinoma |
WO2016205790A2 (en) | 2015-06-19 | 2016-12-22 | Hanlin Scientific, Inc. | Chiral specific boron-containing compounds and their use in treating cancer or amyloidosis |
EP3120837A1 (de) | 2015-07-22 | 2017-01-25 | Stada Arzneimittel Ag | Verfahren zur herstellung einer bortezomibester-lösung |
EP3370719A1 (en) | 2015-11-02 | 2018-09-12 | Novartis AG | Dosage regimen for a phosphatidylinositol 3-kinase inhibitor |
US11111296B2 (en) | 2015-12-14 | 2021-09-07 | The Broad Institute, Inc. | Compositions and methods for treating cardiac dysfunction |
CN107151254A (zh) * | 2016-03-06 | 2017-09-12 | 复旦大学 | 一种作为20s蛋白酶体抑制剂的硼酸类化合物及其制备方法 |
CN107151255A (zh) * | 2016-03-06 | 2017-09-12 | 复旦大学 | 硼酸类化合物及其制备方法和用途 |
MA45479A (fr) | 2016-04-14 | 2019-02-20 | Janssen Biotech Inc | Différenciation de cellules souches pluripotentes en cellules de l'endoderme de l'intestin moyen |
US11447506B2 (en) | 2016-05-09 | 2022-09-20 | Anacor Pharmaceuticals, Inc. | Crystal forms of crisaborole in free form and preparation method and use thereof |
CN106008572B (zh) * | 2016-05-23 | 2018-08-17 | 成都千禧莱医药科技有限公司 | 一类二肽硼酸化合物及制备方法和用途 |
CA3025253A1 (en) | 2016-06-21 | 2017-12-28 | Orion Ophthalmology LLC | Heterocyclic prolinamide derivatives |
US10526315B2 (en) | 2016-06-21 | 2020-01-07 | Orion Ophthalmology LLC | Carbocyclic prolinamide derivatives |
JP6681284B2 (ja) * | 2016-06-23 | 2020-04-15 | 信越化学工業株式会社 | 糖アルコール化合物の金属低減方法 |
JP6223508B2 (ja) * | 2016-06-27 | 2017-11-01 | ミレニアム ファーマシューティカルズ, インコーポレイテッドMillennium Pharmaceuticals, Inc. | プロテアソーム阻害剤 |
WO2018038687A1 (en) | 2016-08-22 | 2018-03-01 | Mustafa Nevzat Ilaç Sanayii A.Ş. | Pharmaceutical formulations comprising a bortezomib-cyclodextrin complex |
WO2018060833A1 (en) | 2016-09-27 | 2018-04-05 | Novartis Ag | Dosage regimen for alpha-isoform selective phosphatidylinositol 3-kinase inhibitor alpelisib |
JP2020500839A (ja) | 2016-10-20 | 2020-01-16 | ファイザー・インク | ペプチドボロン酸またはボロン酸エステル化合物を有する治療用粒子ならびにその作製および使用方法 |
US11584733B2 (en) | 2017-01-09 | 2023-02-21 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
US11034667B2 (en) | 2017-01-09 | 2021-06-15 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
CN110312727A (zh) | 2017-02-17 | 2019-10-08 | 费森尤斯卡比肿瘤学有限公司 | 一种改进的制备硼酸酯的方法 |
CA3054572A1 (en) | 2017-02-28 | 2018-09-07 | Mayo Foundation For Medical Education And Research | Compounds and methods for treating cancer |
CN111601597B (zh) | 2017-08-23 | 2023-10-13 | 科智生命科学公司 | 自身免疫性病症的治疗中的免疫蛋白酶体抑制剂和免疫抑制剂 |
CA3075714A1 (en) | 2017-09-14 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer |
JP2018024694A (ja) * | 2017-10-03 | 2018-02-15 | ミレニアム ファーマシューティカルズ, インコーポレイテッドMillennium Pharmaceuticals, Inc. | プロテアソーム阻害剤 |
HUE060020T2 (hu) * | 2017-11-16 | 2023-01-28 | Principia Biopharma Inc | Immunproteaszóma-gátlók |
EP3710458A1 (en) | 2017-11-16 | 2020-09-23 | Principia Biopharma Inc. | Immunoproteasome inhibitors |
US10537585B2 (en) | 2017-12-18 | 2020-01-21 | Dexcel Pharma Technologies Ltd. | Compositions comprising dexamethasone |
CA3087565A1 (en) | 2018-01-09 | 2019-07-18 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
TW202003553A (zh) | 2018-03-15 | 2020-01-16 | 美商艾伯維有限公司 | 用於治療癌症之abbv-621與抗癌劑之組合 |
US11243207B2 (en) | 2018-03-29 | 2022-02-08 | Mayo Foundation For Medical Education And Research | Assessing and treating cancer |
EP3873214A4 (en) | 2018-10-29 | 2022-07-13 | Forma Therapeutics, Inc. | SOLID FORMS OF (4-(2-FLUORO-4-(1-METHYL-1H-BENZO[D]IMIDAZOL-5-YL)BENZOYL)PIPERAZIN-1-YL)(1-HYDROXYCYCLOPROPYL)METHANONE |
CN109824756B (zh) * | 2019-03-19 | 2022-03-22 | 山东大学 | 含有4-(苯磺酰基)哌嗪-2-酮的苯丙氨酸衍生物及其制备方法与应用 |
WO2022120039A2 (en) * | 2020-12-02 | 2022-06-09 | Steven Hoffman | Compositions and methods for modulating cancer in non-human mammals |
TW202237143A (zh) * | 2020-12-10 | 2022-10-01 | 南韓商Lg化學股份有限公司 | 酸(Boronic Acid)化合物 |
EP4134083A1 (en) | 2021-08-12 | 2023-02-15 | Extrovis AG | Pharmaceutical compositions of bortezomib |
CN113957441B (zh) * | 2021-10-29 | 2024-01-02 | 光华科学技术研究院(广东)有限公司 | 蚀刻液及其制备方法和应用 |
WO2023220655A1 (en) | 2022-05-11 | 2023-11-16 | Celgene Corporation | Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy |
WO2023220641A2 (en) | 2022-05-11 | 2023-11-16 | Juno Therapeutics, Inc. | Methods and uses related to t cell therapy and production of same |
Family Cites Families (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4261868A (en) * | 1979-08-08 | 1981-04-14 | Lever Brothers Company | Stabilized enzymatic liquid detergent composition containing a polyalkanolamine and a boron compound |
US4369183A (en) * | 1979-09-06 | 1983-01-18 | Merck & Co., Inc. | 2-Pyridyl-1,2-benzisothiazolinone-1,1-dioxides and their use as selective protease inhibitors |
US4510130A (en) | 1983-05-20 | 1985-04-09 | Genetic Diagnostics Corporation | Promoting animal and plant growth with leupeptin |
US4499082A (en) * | 1983-12-05 | 1985-02-12 | E. I. Du Pont De Nemours And Company | α-Aminoboronic acid peptides |
US4537773A (en) | 1983-12-05 | 1985-08-27 | E. I. Du Pont De Nemours And Company | α-Aminoboronic acid derivatives |
US4537707A (en) * | 1984-05-14 | 1985-08-27 | The Procter & Gamble Company | Liquid detergents containing boric acid and formate to stabilize enzymes |
US4842769A (en) * | 1985-07-26 | 1989-06-27 | Colgate-Palmolive Co. | Stabilized fabric softening built detergent composition containing enzymes |
US4759032A (en) | 1987-06-03 | 1988-07-19 | Monsanto Company | Electrode seal assembly |
US5187157A (en) * | 1987-06-05 | 1993-02-16 | Du Pont Merck Pharmaceutical Company | Peptide boronic acid inhibitors of trypsin-like proteases |
US5242904A (en) * | 1987-06-05 | 1993-09-07 | The Dupont Merck Pharmaceutical Company | Peptide boronic acid inhibitors of trypsin-like proteases |
US5250720A (en) * | 1987-06-05 | 1993-10-05 | The Dupont Merck Pharmaceutical Company | Intermediates for preparing peptide boronic acid inhibitors of trypsin-like proteases |
SE8702550D0 (sv) * | 1987-06-18 | 1987-06-18 | Anders Grubb | Cysteinproteashemmare |
KR960012512B1 (ko) | 1987-06-19 | 1996-09-20 | 캔디스 엘. 볼커 | 신규한 종류의 저칼로리 단백질 감미제 |
EP0315574A3 (de) | 1987-11-05 | 1990-08-22 | Hoechst Aktiengesellschaft | Renin-Inhibitoren |
US5106948A (en) * | 1988-05-27 | 1992-04-21 | Mao Foundation For Medical Education And Research | Cytotoxic boronic acid peptide analogs |
US4963655A (en) * | 1988-05-27 | 1990-10-16 | Mayo Foundation For Medical Education And Research | Boron analogs of amino acid/peptide protease inhibitors |
DE3827340A1 (de) * | 1988-08-12 | 1990-02-15 | Hoechst Ag | Verwendung von (alpha)-aminoboronsaeure-derivaten zur prophylaxe und behandlung von viruserkrankungen |
ZA897515B (en) * | 1988-10-07 | 1990-06-27 | Merrell Dow Pharma | Novel peptidase inhibitors |
US4997929A (en) * | 1989-01-05 | 1991-03-05 | Synergen, Inc. | Purified ciliary neurotrophic factor |
US4959179A (en) * | 1989-01-30 | 1990-09-25 | Lever Brothers Company | Stabilized enzymes liquid detergent composition containing lipase and protease |
JP2701932B2 (ja) * | 1989-04-10 | 1998-01-21 | サントリー株式会社 | タンパク質分解酵素阻害剤 |
US5030378A (en) * | 1990-01-02 | 1991-07-09 | The Procter & Gamble Company | Liquid detergents containing anionic surfactant, builder and proteolytic enzyme |
CA2077665A1 (en) | 1990-03-05 | 1991-09-06 | Robert Siman | Chymotrypsin-like proteases and their inhibitors |
GB9017694D0 (en) * | 1990-08-13 | 1990-09-26 | Sandoz Ltd | Improvements in or relating to organic chemistry |
EP0478050A1 (en) * | 1990-09-24 | 1992-04-01 | Unilever N.V. | Detergent composition |
GB9024129D0 (en) * | 1990-11-06 | 1990-12-19 | Thrombosis Research Trust | Inhibitors and substrates of thrombin |
EP0564552A1 (en) * | 1990-12-28 | 1993-10-13 | Cortex Pharmaceuticals, Inc. | Use of calpain inhibitors in the inhibition and treatment of neurodegeneration |
JP2703408B2 (ja) | 1990-12-28 | 1998-01-26 | 麒麟麦酒株式会社 | 1,4‐ベンゾチアゼピン誘導体 |
EP0564561A4 (en) * | 1990-12-28 | 1994-08-10 | Georgia Tech Res Inst | Peptides ketoamides, ketoacids, and ketoesters |
EP0511456A1 (en) * | 1991-04-30 | 1992-11-04 | The Procter & Gamble Company | Liquid detergents with aromatic borate ester to inhibit proteolytic enzyme |
AU666660B2 (en) * | 1991-04-30 | 1996-02-22 | Procter & Gamble Company, The | Built liquid detergents with boric-polyol complex to inhibit proteolytic enzyme |
AU2014892A (en) * | 1991-04-30 | 1992-12-21 | Procter & Gamble Company, The | Liquid detergents with an aryl boronic acid |
US5554728A (en) * | 1991-07-23 | 1996-09-10 | Nexstar Pharmaceuticals, Inc. | Lipid conjugates of therapeutic peptides and protease inhibitors |
AU4077193A (en) * | 1992-04-16 | 1993-11-18 | Zeneca Limited | Alpha-aminoboronic acid peptides and their use as elastase inhibitors |
JPH07505877A (ja) * | 1992-04-16 | 1995-06-29 | ゼネカ・リミテッド | α−アミノボロン酸ペプチド及びエラスターゼ阻害剤としてのそれらの使用 |
ES2098484T3 (es) | 1992-08-14 | 1997-05-01 | Procter & Gamble | Detergentes liquidos que contienen un acido alfa-amino-boronico. |
WO1994017816A1 (en) | 1993-02-10 | 1994-08-18 | The President And Fellows Of Harvard College | Role of atp-ubiquitin-dependent proteolysis in mhc-1 restricted antigen presentation and inhibitors thereof |
US5384410A (en) * | 1993-03-24 | 1995-01-24 | The Du Pont Merck Pharmaceutical Company | Removal of boronic acid protecting groups by transesterification |
DE4311835A1 (de) * | 1993-04-07 | 1994-10-13 | Boehringer Ingelheim Int | Verfahren zur Inhibierung der Transkription von Genen |
US5424904A (en) * | 1993-10-04 | 1995-06-13 | Taylor, Sr.; Thomas T. | Circuit for electrically controlled intermittent motion |
IL111176A0 (en) * | 1993-10-07 | 1994-12-29 | Du Pont Merck Pharma | Dipeptide boronic acid inhibitors of trypsin-like enzymes and pharmaceutical compositions containing them |
US5693617A (en) * | 1994-03-15 | 1997-12-02 | Proscript, Inc. | Inhibitors of the 26s proteolytic complex and the 20s proteasome contained therein |
US6660268B1 (en) * | 1994-03-18 | 2003-12-09 | The President And Fellows Of Harvard College | Proteasome regulation of NF-KB activity |
US5574017A (en) | 1994-07-05 | 1996-11-12 | Gutheil; William G. | Antibacterial agents |
US6083903A (en) * | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
US5614649A (en) | 1994-11-14 | 1997-03-25 | Cephalon, Inc. | Multicatalytic protease inhibitors |
US5550262A (en) * | 1994-11-14 | 1996-08-27 | Cephalon, Inc. | Multicatalytic protease inhibitors |
ATE501157T1 (de) | 2001-01-25 | 2011-03-15 | Us Of America Represented By The Secretary Dept Of Health And Human Services | Formulierungen von borsäure-verbindungen |
RS51983B (en) | 2004-03-30 | 2012-02-29 | Millennium Pharmaceuticals Inc. | SYNTHESIS OF ORGANOBORIC ACID AND ORGANOBORIC ACID COMPOUNDS |
-
1995
- 1995-05-16 US US08/442,581 patent/US6083903A/en not_active Expired - Lifetime
- 1995-10-27 NZ NZ337211A patent/NZ337211A/xx not_active IP Right Cessation
- 1995-10-27 CN CNB951965905A patent/CN1305475C/zh not_active Expired - Lifetime
- 1995-10-27 CA CA2496538A patent/CA2496538C/en not_active Expired - Lifetime
- 1995-10-27 PT PT03004280T patent/PT1312609E/pt unknown
- 1995-10-27 EP EP03004280A patent/EP1312609B1/en not_active Expired - Lifetime
- 1995-10-27 PT PT05023462T patent/PT1627880E/pt unknown
- 1995-10-27 IL IL13383195A patent/IL133831A/en not_active IP Right Cessation
- 1995-10-27 ES ES03004280T patent/ES2254803T3/es not_active Expired - Lifetime
- 1995-10-27 EP EP95939670A patent/EP0788360B3/en not_active Expired - Lifetime
- 1995-10-27 ES ES05023462T patent/ES2314540T3/es not_active Expired - Lifetime
- 1995-10-27 TW TW084111436A patent/TW318850B/zh not_active IP Right Cessation
- 1995-10-27 AU AU41398/96A patent/AU710564B2/en not_active Expired
- 1995-10-27 IL IL11579095A patent/IL115790A/en active Protection Beyond IP Right Term
- 1995-10-27 DE DE200412000025 patent/DE122004000025I1/de active Pending
- 1995-10-27 AT AT03004280T patent/ATE314378T1/de active
- 1995-10-27 CN CN2007100887250A patent/CN101077875B/zh not_active Expired - Lifetime
- 1995-10-27 PT PT95939670T patent/PT788360E/pt unknown
- 1995-10-27 IL IL13772695A patent/IL137726A/en not_active IP Right Cessation
- 1995-10-27 AT AT95939670T patent/ATE241631T1/de active
- 1995-10-27 EP EP08016076A patent/EP1997823A1/en not_active Withdrawn
- 1995-10-27 DE DE69534727T patent/DE69534727T2/de not_active Expired - Lifetime
- 1995-10-27 CA CA002203936A patent/CA2203936C/en not_active Expired - Lifetime
- 1995-10-27 AT AT05023462T patent/ATE411324T1/de active
- 1995-10-27 US US08/549,318 patent/US5780454A/en not_active Expired - Lifetime
- 1995-10-27 NZ NZ296717A patent/NZ296717A/en not_active IP Right Cessation
- 1995-10-27 ES ES95939670T patent/ES2199257T7/es active Active
- 1995-10-27 DE DE1995630936 patent/DE122004000025I2/de active Active
- 1995-10-27 DK DK05023462T patent/DK1627880T3/da active
- 1995-10-27 DE DE69530936T patent/DE69530936T3/de not_active Expired - Lifetime
- 1995-10-27 WO PCT/US1995/014117 patent/WO1996013266A1/en active IP Right Grant
- 1995-10-27 JP JP51483496A patent/JP3717934B2/ja not_active Expired - Lifetime
- 1995-10-27 DE DE69535866T patent/DE69535866D1/de not_active Expired - Lifetime
- 1995-10-27 DK DK03004280T patent/DK1312609T3/da active
- 1995-10-27 CH CH95939670T patent/CH0788360H1/de unknown
- 1995-10-27 DK DK95939670.6T patent/DK0788360T5/da active
- 1995-10-27 EP EP05023462A patent/EP1627880B1/en not_active Expired - Lifetime
- 1995-10-27 KR KR1019970702789A patent/KR100398944B1/ko not_active IP Right Cessation
-
1997
- 1997-04-23 FI FI971746A patent/FI114801B/fi active Protection Beyond IP Right Term
- 1997-04-25 MX MX9703063A patent/MX9703063A/es unknown
- 1997-04-25 NO NO19971929A patent/NO310558B1/no not_active IP Right Cessation
-
1998
- 1998-02-07 HK HK98100951A patent/HK1002059A1/xx not_active IP Right Cessation
- 1998-05-26 US US09/085,404 patent/US6066730A/en not_active Expired - Lifetime
-
1999
- 1999-12-30 IL IL13383199A patent/IL133831A0/xx unknown
-
2000
- 2000-01-25 US US09/490,511 patent/US6297217B1/en not_active Expired - Lifetime
- 2000-08-07 IL IL13772600A patent/IL137726A0/xx unknown
-
2001
- 2001-09-14 US US09/953,540 patent/US6465433B1/en not_active Expired - Lifetime
-
2002
- 2002-03-18 US US10/100,295 patent/US6548668B2/en not_active Expired - Lifetime
- 2002-04-19 US US10/125,997 patent/US6617317B1/en not_active Expired - Lifetime
-
2003
- 2003-03-19 US US10/392,165 patent/US6747150B2/en not_active Expired - Lifetime
- 2003-12-08 US US10/730,231 patent/US7119080B2/en not_active Expired - Fee Related
-
2004
- 2004-05-14 NL NL300151C patent/NL300151I2/nl unknown
- 2004-05-19 FR FR04C0014C patent/FR04C0014I2/fr active Active
- 2004-06-09 LU LU91083C patent/LU91083I2/fr unknown
- 2004-08-06 NO NO2004004C patent/NO2004004I2/no not_active IP Right Cessation
- 2004-11-03 FI FI20041415A patent/FI120974B/fi not_active IP Right Cessation
- 2004-11-19 CY CY0400082A patent/CY2484B1/xx unknown
-
2005
- 2005-10-17 US US11/252,291 patent/US20060122390A1/en not_active Abandoned
-
2006
- 2006-07-11 HK HK06107756.3A patent/HK1087714A1/xx not_active IP Right Cessation
- 2006-12-20 US US11/642,372 patent/US20070282100A1/en not_active Abandoned
-
2008
- 2008-01-02 US US12/006,422 patent/US7531526B2/en not_active Expired - Lifetime
-
2009
- 2009-04-01 US US12/416,193 patent/US8003791B2/en not_active Expired - Fee Related
-
2011
- 2011-08-19 US US13/213,157 patent/US8378099B2/en not_active Expired - Fee Related
-
2013
- 2013-01-11 US US13/739,223 patent/US20130310320A1/en not_active Abandoned
-
2014
- 2014-04-08 US US14/247,711 patent/US20150072942A1/en not_active Abandoned
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107474062A (zh) * | 2004-03-30 | 2017-12-15 | 千禧药品公司 | 硼的酯和酸化合物的合成 |
CN103497232A (zh) * | 2008-06-17 | 2014-01-08 | 米伦纽姆医药公司 | 硼酸酯化合物及其医药组合物 |
CN103467565A (zh) * | 2008-06-17 | 2013-12-25 | 米伦纽姆医药公司 | 硼酸酯化合物及其医药组合物 |
CN103450241A (zh) * | 2008-06-17 | 2013-12-18 | 米伦纽姆医药公司 | 硼酸酯化合物及其医药组合物 |
CN103497210A (zh) * | 2008-06-17 | 2014-01-08 | 米伦纽姆医药公司 | 硼酸酯化合物及其医药组合物 |
CN101638414B (zh) * | 2008-07-30 | 2014-01-08 | 江苏先声药物研究有限公司 | 肽硼酸及其酯类化合物、制备方法及其用途 |
CN103554143A (zh) * | 2008-09-29 | 2014-02-05 | 米伦纽姆医药公司 | 1-氨基-2-环丁基乙基硼酸衍生物 |
CN103554143B (zh) * | 2008-09-29 | 2018-02-23 | 米伦纽姆医药公司 | 1‑氨基‑2‑环丁基乙基硼酸衍生物 |
CN101747354B (zh) * | 2008-12-04 | 2014-08-13 | 江苏先声药物研究有限公司 | 一类β氨基酸组成的二肽硼酸及其酯类化合物、制备方法及其用途 |
CN101747354A (zh) * | 2008-12-04 | 2010-06-23 | 江苏先声药物研究有限公司 | 一类β氨基酸组成的二肽硼酸及其酯类化合物、制备方法及其用途 |
CN104822688A (zh) * | 2012-09-11 | 2015-08-05 | 西普拉有限公司 | 制备硼替佐米的方法 |
CN106478700A (zh) * | 2015-08-26 | 2017-03-08 | 杭州雷索药业有限公司 | 硼基取代的苯胺类蛋白激酶抑制剂 |
CN106588965A (zh) * | 2015-10-15 | 2017-04-26 | 北京大学 | 脲拟肽硼酸化合物及其药物组合物、制备方法和用途 |
WO2017063491A1 (zh) * | 2015-10-15 | 2017-04-20 | 北京大学 | 脲拟肽硼酸化合物及其药物组合物、制备方法和用途 |
CN108368133A (zh) * | 2015-10-15 | 2018-08-03 | 北京大学 | 脲拟肽硼酸化合物及其药物组合物、制备方法和用途 |
US10494384B2 (en) | 2015-10-15 | 2019-12-03 | Peking University | Urea peptoid boric acid compound, pharmaceutical composition thereof, preparation method therefor, and uses thereof |
CN108368133B (zh) * | 2015-10-15 | 2020-08-18 | 郑州安双云平医药科技有限公司 | 脲拟肽硼酸化合物及其药物组合物、制备方法和用途 |
WO2022089556A1 (zh) * | 2020-10-30 | 2022-05-05 | 苏州开拓药业股份有限公司 | 一种c-Myc蛋白抑制剂及其制备方法和用途 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1305475C (zh) | 硼酸酯和硼酸化合物,其合成和应用 | |
CN1192035C (zh) | 白介素-1β转化酶抑制剂 | |
US6846806B2 (en) | Peptide inhibitors of Hepatitis C virus NS3 protein | |
CN1134264C (zh) | 抗血栓形成剂 | |
CN1189476C (zh) | 新的凝血酶抑制剂及其制备方法和用途 | |
CN1250566C (zh) | 化学修饰的多肽 | |
CN1633446A (zh) | 用作丙型肝炎病毒ns3-丝氨酸蛋白酶抑制剂的新型肽 | |
CN1839139A (zh) | 蛋白酶体抑制剂及其使用方法 | |
CN1315965A (zh) | 丙型肝炎肽抑制剂 | |
CN1187769A (zh) | 乳胱氨酸类似物 | |
CN1432022A (zh) | 含有烷基和芳基丙氨酸p2部分的丙型肝炎病毒的大环ns3-丝氨酸蛋白酶抑制剂 | |
CN1041951A (zh) | 新的肽酶抑制剂 | |
CN1193978A (zh) | 肽基化合物和它们作为金属蛋白酶抑制剂的医疗用途 | |
CN1085546A (zh) | 胺二醇蛋白酶抑制剂 | |
CN1498224A (zh) | 用作丙型肝炎病毒ns3-丝氨酸蛋白酶抑制剂的新型肽 | |
CN1323203A (zh) | Fc受体调节剂及其应用 | |
CN1372566A (zh) | 抗细小核糖核酸病毒的化合物和组合物,它们的药物用途,及其合成原料 | |
CN1228783A (zh) | 新的凝血酶抑制剂 | |
CN1055537A (zh) | 3,5-双取代-2-异唑烷和异唑、其制备方法,含有该成分的制剂及其应用 | |
CN1212704A (zh) | 丝氨酸蛋白酶抑制剂 | |
CN1047084A (zh) | 具有酶抑制作用的二肽衍生物 | |
CN1289341A (zh) | 凝血酶抑制剂 | |
CN1867572A (zh) | 蛋白酶体抑制剂及其使用方法 | |
CN1086825A (zh) | 三环和四环化合物 | |
CN1237075C (zh) | 用作层粘连蛋白/巢蛋白相互作用抑制剂的低分子量肽衍生物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
ASS | Succession or assignment of patent right |
Owner name: MILLENNIUM MEDICINE CO.,LTD. Free format text: FORMER OWNER: ROCKSET CO.,LTD. Effective date: 20030113 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20030113 Address after: Massachusetts, USA Applicant after: MIllennium Pharmaceuticals Inc Address before: Massachusetts, USA Applicant before: Rocco, Seth |
|
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
CI01 | Publication of corrected invention patent application |
Correction item: Service bar Correct: delete False: deemed to have been withdrawn Number: 44 Page: 459 Volume: 19 |
|
ERR | Gazette correction |
Free format text: CORRECT: AFFAIR COLUMN; FROM: DEEMED WITHDRAWAL TO: DELETION |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term | ||
CX01 | Expiry of patent term |
Granted publication date: 20070321 |