WO2004029055A1 - Fused azole-pyrimidine derivatives - Google Patents

Fused azole-pyrimidine derivatives Download PDF

Info

Publication number: WO2004029055A1
Authority: WO; WIPO (PCT)
Prior art keywords: amino; alkyl; optionally substituted; hydroxy; quinazolin
Prior art date: 2002-09-30

Application number

PCT/EP2003/010377

Other languages

English (en)

French (fr)

Inventor

Mitsuyuki Shimada

Toshiki Murata

Kinji Fuchikami

Hideki Tsujishita

Naoki Omori

Issei Kato

Mami Miura

Klaus Urbahns

Florian Gantner

Kevin Bacon

Original Assignee

Bayer Pharmaceuticals Corporation

Priority date (The priority date 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 date listed.)

2002-09-30

Filing date

2003-09-18

Publication date

2004-04-08

2003-09-18 Priority to JP2004538935A priority Critical patent/JP4790266B2/ja

2003-09-18 Priority to NZ539062A priority patent/NZ539062A/en

2003-09-18 Priority to DK03788908T priority patent/DK1549652T3/da

2003-09-18 Priority to KR1020057005434A priority patent/KR101059652B1/ko

2003-09-18 Priority to BRPI0314830A priority patent/BRPI0314830B8/pt

2003-09-18 Priority to UAA200504176A priority patent/UA82205C2/uk

2003-09-18 Priority to CA2499134A priority patent/CA2499134C/en

2003-09-18 Priority to DE60324296T priority patent/DE60324296D1/de

2003-09-18 Priority to US10/527,376 priority patent/US7511041B2/en

2003-09-18 Priority to MXPA05001808A priority patent/MXPA05001808A/es

2003-09-18 Application filed by Bayer Pharmaceuticals Corporation filed Critical Bayer Pharmaceuticals Corporation

2003-09-18 Priority to SI200331490T priority patent/SI1549652T1/sl

2003-09-18 Priority to EP03788908A priority patent/EP1549652B1/en

2003-09-18 Priority to AU2003293310A priority patent/AU2003293310B2/en

2003-09-18 Priority to PL375935A priority patent/PL226562B1/pl

2004-04-08 Publication of WO2004029055A1 publication Critical patent/WO2004029055A1/en

2005-02-14 Priority to IL166855A priority patent/IL166855A/en

2005-04-27 Priority to HRP20050375AA priority patent/HRP20050375B1/hr

2005-04-27 Priority to NO20052076A priority patent/NO331457B1/no

2006-04-19 Priority to HK06104675.8A priority patent/HK1084393A1/xx

2009-03-30 Priority to US12/414,257 priority patent/US8129386B2/en

2013-12-04 Priority to HRP20131159A priority patent/HRP20131159B1/hr

Links

DDWJFSYHYPDQEL-UHFFFAOYSA-N pyrimidine;1h-pyrrole Chemical class C=1C=CNC=1.C1=CN=CN=C1 DDWJFSYHYPDQEL-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 109
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
238000000034 method Methods 0.000 claims abstract description 27
238000011282 treatment Methods 0.000 claims abstract description 21
230000000694 effects Effects 0.000 claims abstract description 19
208000035475 disorder Diseases 0.000 claims abstract description 16
201000010099 disease Diseases 0.000 claims abstract description 11
208000028867 ischemia Diseases 0.000 claims abstract description 11
238000011321 prophylaxis Methods 0.000 claims abstract description 10
206010028980 Neoplasm Diseases 0.000 claims abstract description 9
230000002107 myocardial effect Effects 0.000 claims abstract description 9
206010019280 Heart failures Diseases 0.000 claims abstract description 8
241001465754 Metazoa Species 0.000 claims abstract description 8
201000011510 cancer Diseases 0.000 claims abstract description 8
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 8
206010007572 Cardiac hypertrophy Diseases 0.000 claims abstract description 7
208000006029 Cardiomegaly Diseases 0.000 claims abstract description 7
208000001647 Renal Insufficiency Diseases 0.000 claims abstract description 7
208000026935 allergic disease Diseases 0.000 claims abstract description 7
208000006673 asthma Diseases 0.000 claims abstract description 7
201000006370 kidney failure Diseases 0.000 claims abstract description 7
230000007170 pathology Effects 0.000 claims abstract description 7
208000002815 pulmonary hypertension Diseases 0.000 claims abstract description 7
206010039083 rhinitis Diseases 0.000 claims abstract description 7
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 6
230000002757 inflammatory effect Effects 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 6
208000015023 Graves' disease Diseases 0.000 claims abstract description 5
230000004957 immunoregulator effect Effects 0.000 claims abstract description 5
206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 5
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 4
208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 4
-1 nitro, hydroxy, cyano, carboxy, amino Chemical group 0.000 claims description 299
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 215
125000000217 alkyl group Chemical group 0.000 claims description 105
229910052736 halogen Inorganic materials 0.000 claims description 67
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 59
125000003545 alkoxy group Chemical group 0.000 claims description 53
229910052739 hydrogen Inorganic materials 0.000 claims description 53
239000001257 hydrogen Substances 0.000 claims description 53
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 49
230000002401 inhibitory effect Effects 0.000 claims description 45
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
150000002367 halogens Chemical class 0.000 claims description 31
125000001424 substituent group Chemical group 0.000 claims description 31
235000005152 nicotinamide Nutrition 0.000 claims description 30
239000011570 nicotinamide Substances 0.000 claims description 30
229960003966 nicotinamide Drugs 0.000 claims description 30
125000003118 aryl group Chemical group 0.000 claims description 26
125000004193 piperazinyl group Chemical group 0.000 claims description 25
239000000126 substance Substances 0.000 claims description 24
125000004093 cyano group Chemical group *C#N 0.000 claims description 22
125000004076 pyridyl group Chemical group 0.000 claims description 22
125000001544 thienyl group Chemical group 0.000 claims description 18
239000003814 drug Substances 0.000 claims description 17
125000003226 pyrazolyl group Chemical group 0.000 claims description 17
125000005842 heteroatom Chemical group 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
125000002883 imidazolyl group Chemical group 0.000 claims description 15
229910052760 oxygen Inorganic materials 0.000 claims description 15
125000000168 pyrrolyl group Chemical group 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 15
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 15
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 14
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
229920006395 saturated elastomer Polymers 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 13
125000002252 acyl group Chemical group 0.000 claims description 12
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 12
125000003831 tetrazolyl group Chemical group 0.000 claims description 12
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
125000001309 chloro group Chemical group Cl* 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
239000004480 active ingredient Substances 0.000 claims description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 9
125000004414 alkyl thio group Chemical group 0.000 claims description 9
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 9
150000002431 hydrogen Chemical group 0.000 claims description 9
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
125000001041 indolyl group Chemical group 0.000 claims description 8
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
125000004043 oxo group Chemical group O=* 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 8
125000003386 piperidinyl group Chemical group 0.000 claims description 8
125000003373 pyrazinyl group Chemical group 0.000 claims description 8
125000002098 pyridazinyl group Chemical group 0.000 claims description 8
125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
125000000335 thiazolyl group Chemical group 0.000 claims description 8
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 claims description 7
108091007960 PI3Ks Proteins 0.000 claims description 7
125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 claims description 7
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 7
125000002541 furyl group Chemical group 0.000 claims description 7
208000027866 inflammatory disease Diseases 0.000 claims description 7
125000000842 isoxazolyl group Chemical group 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
125000004423 acyloxy group Chemical group 0.000 claims description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
125000005466 alkylenyl group Chemical group 0.000 claims description 6
230000001363 autoimmune Effects 0.000 claims description 6
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
125000001072 heteroaryl group Chemical group 0.000 claims description 6
125000004171 alkoxy aryl group Chemical group 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
239000003112 inhibitor Substances 0.000 claims description 5
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 5
229920002554 vinyl polymer Polymers 0.000 claims description 5
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical group C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 4
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical group C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 4
125000005529 alkyleneoxy group Chemical group 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
125000001475 halogen functional group Chemical group 0.000 claims description 4
125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
125000002971 oxazolyl group Chemical group 0.000 claims description 4
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
125000005493 quinolyl group Chemical group 0.000 claims description 4
229940124530 sulfonamide Drugs 0.000 claims description 4
150000003456 sulfonamides Chemical class 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 3
125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 3
125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 3
125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 3
125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 claims description 3
125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 3
125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 3
GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 claims description 3
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
125000001786 isothiazolyl group Chemical group 0.000 claims description 3
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
XNBBGYUSKXEZLX-UHFFFAOYSA-N N=1C=2C(OC)=C(OCC(=O)N(C)C)C=CC=2C2=NCCN2C=1C=C(O)C1=CC=CN=C1 Chemical compound N=1C=2C(OC)=C(OCC(=O)N(C)C)C=CC=2C2=NCCN2C=1C=C(O)C1=CC=CN=C1 XNBBGYUSKXEZLX-UHFFFAOYSA-N 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 20
230000002265 prevention Effects 0.000 claims 5
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 3
102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims 2
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims 1
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims 1
FNLQDVXHDNFXIY-UHFFFAOYSA-N 3h-benzimidazole-5-carboxamide Chemical compound NC(=O)C1=CC=C2NC=NC2=C1 FNLQDVXHDNFXIY-UHFFFAOYSA-N 0.000 claims 1
208000003807 Graves Disease Diseases 0.000 claims 1
125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
125000002837 carbocyclic group Chemical group 0.000 claims 1
HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims 1
OYLANDUSDVCRTH-UHFFFAOYSA-N n-(7,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-3h-benzimidazole-5-carboxamide Chemical compound C1=C2NC=NC2=CC(C(=O)NC2=NC3=C(OC)C=C(C=C3C3=NCCN32)OC)=C1 OYLANDUSDVCRTH-UHFFFAOYSA-N 0.000 claims 1
LUNNURQBAPDEMI-UHFFFAOYSA-N n-(7-bromo-8-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide Chemical compound N=1C2=C(Br)C(OC)=CC=C2C2=NCCN2C=1NC(=O)C1=CC=CN=C1 LUNNURQBAPDEMI-UHFFFAOYSA-N 0.000 claims 1
230000005764 inhibitory process Effects 0.000 abstract description 17
208000023328 Basedow disease Diseases 0.000 abstract description 4
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 abstract description 4
206010012438 Dermatitis atopic Diseases 0.000 abstract description 4
208000005189 Embolism Diseases 0.000 abstract description 4
208000012659 Joint disease Diseases 0.000 abstract description 4
206010040070 Septic Shock Diseases 0.000 abstract description 4
208000001435 Thromboembolism Diseases 0.000 abstract description 4
201000008937 atopic dermatitis Diseases 0.000 abstract description 4
230000036303 septic shock Effects 0.000 abstract description 4
208000018737 Parkinson disease Diseases 0.000 abstract description 3
239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
150000007980 azole derivatives Chemical class 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 75
239000000203 mixture Substances 0.000 description 53
239000000243 solution Substances 0.000 description 46
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
238000006243 chemical reaction Methods 0.000 description 42
238000000338 in vitro Methods 0.000 description 41
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
239000007787 solid Substances 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
210000004027 cell Anatomy 0.000 description 30
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
235000002639 sodium chloride Nutrition 0.000 description 26
239000002904 solvent Substances 0.000 description 26
239000011541 reaction mixture Substances 0.000 description 23
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
238000004949 mass spectrometry Methods 0.000 description 19
238000002844 melting Methods 0.000 description 19
230000008018 melting Effects 0.000 description 19
239000002244 precipitate Substances 0.000 description 19
238000005160 1H NMR spectroscopy Methods 0.000 description 17
125000002887 hydroxy group Chemical group [H]O* 0.000 description 17
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
230000002829 reductive effect Effects 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000000725 suspension Substances 0.000 description 15
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 14
239000012267 brine Substances 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
238000012360 testing method Methods 0.000 description 12
241000699670 Mus sp. Species 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
230000035605 chemotaxis Effects 0.000 description 11
229910052943 magnesium sulfate Inorganic materials 0.000 description 11
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
239000012981 Hank's balanced salt solution Substances 0.000 description 10
238000001914 filtration Methods 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
238000000021 kinase assay Methods 0.000 description 9
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 8
108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 8
238000001816 cooling Methods 0.000 description 8
210000000224 granular leucocyte Anatomy 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
150000004945 aromatic hydrocarbons Chemical class 0.000 description 7
238000003556 assay Methods 0.000 description 7
PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 7
150000002170 ethers Chemical class 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
229960001866 silicon dioxide Drugs 0.000 description 7
239000003981 vehicle Substances 0.000 description 7
239000008096 xylene Substances 0.000 description 7
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
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238000011830 transgenic mouse model Methods 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
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Classifications

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- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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PCT/EP2003/010377 2002-09-30 2003-09-18 Fused azole-pyrimidine derivatives WO2004029055A1 (en)

Priority Applications (20)

Application Number	Priority Date	Filing Date	Title
SI200331490T SI1549652T1 (sl)	2002-09-30	2003-09-18	Kondenzirani azolpirimidinski derivati
NZ539062A NZ539062A (en)	2002-09-30	2003-09-18	Fused azole-pyrimidine derivatives exhibiting enhanced potency for phosphotidylinositol-3-kinase (P13K) inhibition
KR1020057005434A KR101059652B1 (ko)	2002-09-30	2003-09-18	접합 아졸-피리미딘 유도체
BRPI0314830A BRPI0314830B8 (pt)	2002-09-30	2003-09-18	derivados de azol-pirimidina fundida
UAA200504176A UA82205C2 (en)	2002-09-30	2003-09-18	Fused azole-pyrimidine derivatives
CA2499134A CA2499134C (en)	2002-09-30	2003-09-18	Fused azole-pyrimidine derivatives
DE60324296T DE60324296D1 (de)	2002-09-30	2003-09-18	Kondensierte azolpyrimidinderivate
EP03788908A EP1549652B1 (en)	2002-09-30	2003-09-18	Fused azole-pyrimidine derivatives
MXPA05001808A MXPA05001808A (es)	2002-09-30	2003-09-18	Derivados de azol-pirimidina condensados.
JP2004538935A JP4790266B2 (ja)	2002-09-30	2003-09-18	縮合アゾールピリミジン誘導体
DK03788908T DK1549652T3 (da)	2002-09-30	2003-09-18	Kondenserede azolpyrimidinderivater
US10/527,376 US7511041B2 (en)	2002-09-30	2003-09-18	Fused azole-pyrimidine derivatives
AU2003293310A AU2003293310B2 (en)	2002-09-30	2003-09-18	Fused azole-pyrimidine derivatives
PL375935A PL226562B1 (pl)	2002-09-30	2003-09-18	Skondensowane pochodne azolopirymidyn, leki zawierające takie pochodne oraz ich zastosowanie
IL166855A IL166855A (en)	2002-09-30	2005-02-14	Annals of compressed pyrimidine with azaleas that inhibit pi3k activity and drugs containing them.
HRP20050375AA HRP20050375B1 (hr)	2002-09-30	2005-04-27	Taljeni azol-pirimidin derivati
NO20052076A NO331457B1 (no)	2002-09-30	2005-04-27	Kondenserte azolpyrimidinderivater, anvendelse derav og medikament omfattende en slik forbindelse
HK06104675.8A HK1084393A1 (en)	2002-09-30	2006-04-19	Fused azole-pyrimidine derivatives
US12/414,257 US8129386B2 (en)	2002-09-30	2009-03-30	Fused azole-pyrimidine derivatives
HRP20131159A HRP20131159B1 (hr)	2002-09-30	2013-12-04	Taljeni azol-pirimidin derivati

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP02021861.6		2002-09-30
EP02021861		2002-09-30

Related Child Applications (2)

Application Number	Title	Priority Date	Filing Date
US10527376 A-371-Of-International		2003-09-18
US12/414,257 Continuation US8129386B2 (en)	2002-09-30	2009-03-30	Fused azole-pyrimidine derivatives

Publications (1)

Publication Number	Publication Date
WO2004029055A1 true WO2004029055A1 (en)	2004-04-08

Family

ID=32039115

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PCT/EP2003/010377 WO2004029055A1 (en)	2002-09-30	2003-09-18	Fused azole-pyrimidine derivatives

Country Status (33)

Country	Link
US (2)	US7511041B2 (und)
EP (2)	EP1549652B1 (und)
JP (1)	JP4790266B2 (und)
KR (1)	KR101059652B1 (und)
CN (1)	CN100384846C (und)
AR (2)	AR041426A1 (und)
AT (2)	ATE511510T1 (und)
AU (1)	AU2003293310B2 (und)
BR (1)	BRPI0314830B8 (und)
CA (1)	CA2499134C (und)
CY (2)	CY1109790T1 (und)
DE (1)	DE60324296D1 (und)
DK (2)	DK1549652T3 (und)
EC (2)	ECSP055768A (und)
ES (2)	ES2367141T3 (und)
HK (1)	HK1084393A1 (und)
HR (2)	HRP20050375B1 (und)
IL (1)	IL166855A (und)
MA (1)	MA27483A1 (und)
MX (1)	MXPA05001808A (und)
MY (1)	MY140756A (und)
NO (1)	NO331457B1 (und)
NZ (1)	NZ539062A (und)
PE (1)	PE20050089A1 (und)
PL (1)	PL226562B1 (und)
PT (2)	PT1549652E (und)
RU (1)	RU2326881C9 (und)
SI (2)	SI1549652T1 (und)
TW (1)	TWI327570B (und)
UA (1)	UA82205C2 (und)
UY (1)	UY28001A1 (und)
WO (1)	WO2004029055A1 (und)
ZA (1)	ZA200503306B (und)

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