DE69530936C5 - Boronsäure-und-esterverbindungen, deren systhese und verwendungen - Google Patents

Boronsäure-und-esterverbindungen, deren systhese und verwendungen Download PDF

Info

Publication number
DE69530936C5
DE69530936C5 DE69530936T DE69530936T DE69530936C5 DE 69530936 C5 DE69530936 C5 DE 69530936C5 DE 69530936 T DE69530936 T DE 69530936T DE 69530936 T DE69530936 T DE 69530936T DE 69530936 C5 DE69530936 C5 DE 69530936C5
Authority
DE
Germany
Prior art keywords
alkyl
compound according
aryl
carbonyl
hydrogen
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.)
Expired - Lifetime
Application number
DE69530936T
Other languages
English (en)
Other versions
DE69530936T2 (de
DE69530936D1 (de
DE122004000025I2 (de
DE69530936T3 (de
Inventor
Julian Adams
Yu-Ting Ma
Ross Stein
Matthew Baevsky
Louis Grenier
Louis Plamondon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Millennium Pharmaceuticals Inc
Original Assignee
Millennium Pharmaceuticals Inc
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.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26987313&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DE69530936(C5) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Millennium Pharmaceuticals Inc filed Critical Millennium Pharmaceuticals Inc
Publication of DE69530936D1 publication Critical patent/DE69530936D1/de
Publication of DE69530936T2 publication Critical patent/DE69530936T2/de
Publication of DE69530936C5 publication Critical patent/DE69530936C5/de
Application granted granted Critical
Publication of DE69530936T3 publication Critical patent/DE69530936T3/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/33—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
    • 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
    • C07F5/025—Boronic and borinic acid compounds
    • 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

Verbindung mit der Formel:
Figure 00000001
oder ein pharmazeutisch annehmbares Salz derselben; worin
P darstellt R7-C(O)-, R7-NH-C(O)-, R7-O-C(O)- oder R7-SO2, worin R7 Heteroaryl bedeutet, oder dann, wenn P R7-C(O)- ist, auch N-Morpholinyl sein kann;
B1 bei jedem Auftreten unabhängig eines von N oder CH sein kann;
X1 bei jedem Auftreten unabhängig eines von -C(O)-NH-, -CH2-NH-, -CH(OH) -CH2-, -CH(OH)-CH(OH)-, -CH(OH)-CH2-NH-, -CH=CH-, C(O)-CH2-, SO2-NH-, -SO2-CH2- oder -CH(OH)-CH2-C(O)-NH- ist, mit der Maßgabe, dass dann, wenn B1 N darstellt, dass an dieses B1 angeheftete X1 -C(O)-NH- bedeutet;
X2 eines von -C(O)-NH-, -CH(OH)-CH2-, -CH(OH)-CH(OH)-, -C(O)-CH2-, SO2-NH-, -SO2-CH2- oder -CH(OH)-CH2-C(O)-NH- ist,
R Wasserstoff oder Alkyl darstellt oder R zusammen mit dem benachbarten R1 oder dann, wenn A 0 ist, zusammen mit dem benachbarten R2 ein Stickstoff enthaltendes mono-, bi- oder trizyklisches, gesättigtes oder teilweise gesättigtes Ringsystem mit 4 bis 14 Ringgliedern bildet, das wahlweise mit einem oder zweien unter Keto, Hydroxy, Alkyl, Aryl,...

Description

  • Das europäische Patent 0 788 360 mit Wirkung für die Bundesrepublik Deutschland (nationale Patentnummer 695 30 936) wurde im Patentanspruch 1 beschränkt.

Claims (27)

  1. Verbindung mit der Formel:
    Figure 00020001
    oder ein pharmazeutisch annehmbares Salz derselben; worin P darstellt R7-C(O)-, R7-NH-C(O)-, R7-O-C(O)- oder R7-SO2, worin R7 Heteroaryl bedeutet, oder dann, wenn P R7-C(O)- ist, auch N-Morpholinyl sein kann; B1 bei jedem Auftreten unabhängig eines von N oder CH sein kann; X1 bei jedem Auftreten unabhängig eines von -C(O)-NH-, -CH2-NH-, -CH(OH) -CH2-, -CH(OH)-CH(OH)-, -CH(OH)-CH2-NH-, -CH=CH-, C(O)-CH2-, SO2-NH-, -SO2-CH2- oder -CH(OH)-CH2-C(O)-NH- ist, mit der Maßgabe, dass dann, wenn B1 N darstellt, dass an dieses B1 angeheftete X1 -C(O)-NH- bedeutet; X2 eines von -C(O)-NH-, -CH(OH)-CH2-, -CH(OH)-CH(OH)-, -C(O)-CH2-, SO2-NH-, -SO2-CH2- oder -CH(OH)-CH2-C(O)-NH- ist, R Wasserstoff oder Alkyl darstellt oder R zusammen mit dem benachbarten R1 oder dann, wenn A 0 ist, zusammen mit dem benachbarten R2 ein Stickstoff enthaltendes mono-, bi- oder trizyklisches, gesättigtes oder teilweise gesättigtes Ringsystem mit 4 bis 14 Ringgliedern bildet, das wahlweise mit einem oder zweien unter Keto, Hydroxy, Alkyl, Aryl, Aralkyl, Alkoxy oder Aryloxy substituiert sein kann; R1 bei jedem Auftreten unabhängig eines von Wasserstoff, Alkyl, Cycloalkyl, Aryl, einem 5- bis 10-gliedrigen gesättigten, teilweise ungesättigten oder aromatischen Heterozyklus oder -CH2-R5 darstellt, worin der Ringteil von jedem dieser Aryl, Aralkyl, Alkylaryl oder Heterozyklen wahlweise substituiert sein kann; R2 eines von Wasserstoff, Alkyl, Cycloalkyl, Aryl, einem 5- bis 10-gliedrigen gesättigten, teilweise ungesättigten oder aromatischen Heterozyklus oder -CH2-R5 darstellt, worin der Ringteil von jedem dieser Aryl, Aralkyl, Alkylaryl oder Heterozyklen wahlweise substituiert sein kann; R3 eines von Wasserstoff, Alkyl, Cycloalkyl, Aryl, einem 5- bis 10-gliedrigen gesättigten, teilweise ungesättigten oder aromatischen Heterozyklus oder -CH2-R5 darstellt, worin der Ringteil von jedem dieser Aryl, Aralkyl, Alkylaryl oder Heterozyklen wahlweise substituiert sein kann; R5 in jedem Falle eines von Aryl, Aralkyl, Alkylaryl, Zykloalkyl, einem 5- bis 10-gliedrigen gesättigten, teilweise ungesättigten oder aromatischen Heterozyklus oder -W-R6 darstellt, worin W ein Chalcogen und R6 ein Alkyl ist, worin der Ringteil von jedem dieser Aryl, Aralkyl, Alkylaryl oder Heterozyklen wahlweise substituierte sein kann; Z1 und Z2 unabhängig voneinander eines von Alkyl, Hydroxy, Alkoxy oder Aryloxy darstellen oder Z1 und Z2 zusammen eine Einheit bilden, abgeleitet von einer Dihydroxyverbindung mit mindestens zwei Hydroxygruppen, getrennt über mindestens zwei verbindende Atome in einer Kette oder einem Ring, wobei die Kette oder der Ring Kohlenstoffatome und wahlweise ein Heteroatom oder Heteroatome umfasst, die sein können N, S oder O; und A 0, 1 oder 2 ist.
  2. Verbindung gemäß Anspruch 1, worin die Heteroarylgruppe in R7 ausgewählt ist aus der Gruppe, bestehend aus Thienyl, Benzo[b]thienyl, Naphto[2,3-b]thienyl, Thianthrenyl, Furyl, Pyranyl, Isobenzofuranyl, Benzoxazolyl, Chromenyl, Xanthenyl, Phenoxathiinyl, 2H-Pyrrolyl, Pyrrolyl, Imidazolyl, Pyrazolyl, Pyridyl, Pyrazinyl, Pyrimidinyl, Pyridazinyl, Indolizinyl, Isoindolyl, 3H-Indolyl, Indolyl, Indazolyl, Purinyl, 4H-Chinolizinyl, Isochinolyl, Chinolyl, Phthalazinyl, Naphthyridinyl, Chinazolinyl, Cinnolinyl, Pteridinyl, 4aH-Carbazolyl, Carbazolyl, β-Carbolinyl, Phenanthridinyl, Acridinyl, Perimidinyl, Phenanthrolinyl, Phenazinyl, Isothiazolyl, Phenothiazinyl, Isoxazolyl, Furazinyl und Phenoxazinyl.
  3. Verbindung nach Anspruch 1, worin P eines von Chinolincarbonyl, Pyridincarbonyl, Chinolinsulfonyl, Chinoxalincarbonyl, Chinoxalinsulfonyl, Pyrazincarbonyl, Pyrazinsulfonyl, Furancarbonyl, Furansulfonyl oder N-Morpholinylcarbonyl ist.
  4. Verbindung nach Anspruch 1, worin P eines von 8-Chinolincarbonyl, 8-Chinolinsulfonyl, 2-Chinoxalincarbonyl, 2-Chinoxalinsulfonyl, 2-Pyrazincarbonyl, 2-Pyrazinsulfonyl, 3-Furancarbonyl, 3-Furansulfonyl oder N-Morpholincarbonyl ist.
  5. Verbindung nach Anspruch 1, worin A 0 ist.
  6. Verbindung nach Anspruch 1, worin B1 bei jedem Auftreten CH bedeutet.
  7. Verbindung nach Anspruch 6, worin X1 bei jedem Auftreten -C(O)-NH- bedeutet.
  8. Verbindung gemäß Anspruch 7, worin X2 -C(O)-NH- bedeutet.
  9. Verbindung nach Anspruch 1, worin R Wasserstoff oder C1-8-Alkyl ist.
  10. Verbindung nach Anspruch 1, worin: R1 bei jedem Auftreten sowie R2 und R3 jeweils unabhängig eines unter Wasserstoff, C1-8-Alkyl, C3-10-Cycloalkyl, C6-10-Aryl, eine 5-, 6-, 9- oder 10-gliedrige Heteroarylgruppe oder -CH2-R5 darstellen; R5 in jedem Falle eines von C6-10-Aryl, C6-10-Ar(C1-6)alkyl, C1-6-Alk(C6-10)aryl, C3-10-Cycloalkyl, C1-8-Alkoxy, C1-8-Alkylthio oder eine 5-, 6-, 9- oder 10-gliedrige Heteroarylgruppe ist; worin der Ringteil von jedem Aryl, Aralkyl, Alkaryl oder jeder 5-, 6-, 9- oder 10-gliedrigen Heteroarylgruppe von R1, R2, R3 und R5 wahlweise substituiert sein kann durch ein oder zwei Substituenten, unabhängig ausgewählt aus der Gruppe, bestehend aus C1-6-Alkyl, C3-8-Cycloalkyl, C1-6-Alkyl(C3-8)cycloalkyl, C2-8-Alkenyl, C2-8-Alkynyl, Cyano, Amino, C1-6-Alkylamino, Di(C1-6)alkylamino, Benzylamino, Dibenzylamino, Nitro, Carboxy, Carbo(C1-6)alkoxy, Trifluoromethyl, Halogen, C1-6-Alkoxy, C6-10-Aryl, C6-10-Aryl(C1-6)alkyl, C6-10-Aryl(C1-6)alkoxy, Hydroxy, C1-6-Alkylthio, C1-6-Alkylsulfinyl, C1-6-Alkylsulfonyl, C6-10-Arylthio, C6-10-Arylsulfinyl, C6-10-Arylsulfonyl, C6-10-Aryl, C1-6-Alkyl(C6-10)aryl und Halo(C6-10)-Aryl.
  11. Verbindung nach Anspruch 1, worin: A 0 ist; X2 -C(O)-NH- bedeutet; R Wasserstoff oder C1-8-Alkyl darstellt; und R3 C1-6-Alkyl ist.
  12. Verbindung nach Anspruch 1, worin R3 C1-12-Alkyl ist.
  13. Verbindung nach Anspruch 1, worin R3 C1-6-Alkyl ist.
  14. Verbindung nach Anspruch 1, worin R3 C4-Alkyl ist.
  15. Verbindung nach Anspruch 1, worin R3 Isobutyl ist.
  16. Verbindung nach Anspruch 1, worin R2 eines von Isobutyl, 1-Naphthylmethyl, 2-Naphthylmethyl, 3-Pyridylmethyl, 2-Pyridylmethyl, 6-Chinolinylmethyl, 3-Indolylmethyl, Benzyl, 4-Fluorobenzyl, 4-Hydroxybenzyl, 4-(2'-Pyridylmethoxy)-benzyl, 4-(Benzyloxy)benzyl, Benzylnaphthylmethyl oder Phenethyl ist.
  17. Verbindung nach Anspruch 1, worin Z1 und Z2 unabhängig voneinander eines von C1-6-Alkyl, Hydroxy, C1-6-Alkoxy oder C6-10-Aryloxy darstellen.
  18. Verbindung nach Anspruch 16, worin Z1 und Z2 beide Hydroxy bedeuten.
  19. Verbindung nach Anspruch 1, worin Z1 und Z2 zusammen eine Einheit bilden, abgeleitet von einer Dihydroxyverbindung, ausgewählt aus der Gruppe, bestehend aus Pinacol, Perfluoropinacol, Pinandiol, Ethylenglykol, Diethylenglykol, 1,2-Cyclohexandiol, 1,3-Propandiol, 2,3-Butandiol, Glycerin oder Diethanolamin.
  20. Verbindung nach Anspruch 1, worin P eines von Chinolincarbonyl, Pyridincarbonyl, Chinolinsulfonyl, Chinoxalincarbonyl, Chinoxalinsulfonyl, Pyrazincarbonyl, Pyrazinsulfonyl, Furancarbonyl, Furansulfonyl oder N-Morpholincarbonyl ist; A 0 ist; X2 -C(O)-NH- bedeutet; R Wasserstoff oder C1-8-Alkyl ist; R2 und R3 jeweils unabhängig eines von Wasserstoff, C1-8-Alkyl, C3-10-Cycloalkyl, C6-10-Aryl, C6-10-Ar(C1-6)alkyl, Pyridylmethyl oder Chinolinylmethyl darstellen; und Z1 und Z2 beide bedeuten Hydroxy, C1-6-Alkoxy oder C6-10-Aryloxy oder Z1 und Z2 zusammengenommen eine Einheit bilden, abgeleitet von einer Dihydroxyverbindung, ausgewählt aus der Gruppe, bestehend aus Pinacol, Perfluoropinacol, Pinandiol, Ethylenglykol, Diethylenglykol, 1,2-Cyclohexandiol, 1,3-Propandiol, 2,3-Butandiol, Glycerin oder Diethanolamin.
  21. Verbindung nach Anspruch 1, worin: P eines von 8-Chinolincarbonyl, 8-Chinolinsulfonyl, 2-Chinoxalincarbonyl, 2-Chinoxalinsulfonyl, 2-Pyrazincarbonyl, 2-Pyrazinsulfonyl, 3-Pyridincarbonyl, 3-Pyridinsulfonyl, 3-Furancarbonyl, 3-Furansulfonyl oder N-Morpholincarbonyl ist; A 0 ist; X2 -C(O)-NH- bedeutet; R Wasserstoff oder C1-8-Alkyl ist; R3 Isobutyl darstellt; R2 eines von Isobutyl, 1-Naphthylmethyl, 2-Naphthylmethyl, 3-Pyridylmethyl, 2-Pyridylmethyl, 6-Chinolinylmethyl, 3-Indolylmethyl, Benzyl, 4-Fluorobenzyl, 4-Hydroxybenzyl, 4-(2'-Pyridylmethoxy)benzyl, 4-(Benzyloxy)benzyl, Benzylnaphthylmethyl oder Phenethyl ist; und Z1 und Z2 unabhängig eines von Hydroxy, C1-6-Alkoxy, C6-10-Aryloxy darstellen oder Z1 und Z2 zusammengenommen eine Einheit bilden, abgeleitet von einer Dihydroxyverbindung, ausgewählt aus der Gruppe, bestehend aus Pinacol, Perfluoropinacol, Pinandiol, Ethylenglykol, Diethylenglykol, 1,2-Cyclohexandiol, 1,3-Propandiol, 2,3-Butandiol, Glycerin oder Diethanolamin.
  22. Verbindung nach Anspruch 1, worin die Verbindung eine ist von: N-(2-Pyrazin)carbonyl-L-phenylalanin-L-leucinborsäure, N-(2-Chinolin)sulfonyl-L-homophenylalanin-L-leucinborsäure, N-(3-Pyridin)carbonyl-L-phenylalanin-L-leucinborsäure, N-(4-Morpholin)carbonyl-L-phenylalanin-L-leucinborsäure, N-(4-Morpholin)carbonyl-β-(1-naphthyl)-L-alanin-L-leucinborsäure, N-(8-Chinolin)sulfonyl-β-(1-naphthyl)-L-alanin-L-leucinborsäure, N-(4-Morpholin)carbonyl-(O-benzyl)-L-tyrosin-L-leucinborsäure, N-(4-Morpholin)carbonyl-L-tyrosin-L-leucinborsäure, N-(4-Morpholin)carbonyl-[O-(2-pyridylmethyl)]-L-tyrosin-L-leucinborsäure; oder ein pharmazeutisch annehmbares Salz oder ein Boronatester derselben.
  23. Verbindung nach Anspruch 22, worin die Verbindung N-(2-Pyrazin)carbonyl-L-phenylalanin-L-leucinborsäure oder ein pharmazeutisch annehmbares Salz oder ein Boronatester derselben ist.
  24. Pharmazeutische Zubereitung, umfassend eine Verbindung nach einem der vorstehenden Ansprüche oder ein pharmazeutisch annehmbares Salz derselben und einen pharmazeutisch annehmbaren Träger oder Verdünner.
  25. Pharmazeutische Zubereitung nach Anspruch 24, worin die Verbindung in einer Menge vorliegt, die zum Inhibieren der Proteasomenfunktion in einem Säuger wirksam ist.
  26. Verwendung einer Verbindung, wie in einem der Ansprüche 1 bis 23 beansprucht, zur Herstellung einer pharmazeutischen Zubereitung für eine Behandlung, ausgewählt unter: (a) Inhibieren des Wachstums einer Krebszelle; (b) Verringern der Geschwindigkeit des Muskelproteinabbaus; (c) Verringern der Aktivität von NF-κB in einer Zelle; (d) Verringern der Rate des intrazellulären Proteinabbaus; (e) Verringern der Geschwindigkeit des Abbaus von p53; (f) Inhibieren des Zyklin-Abbaus in einer Zelle; (g) Vorbeugen oder Behandeln eines entzündlichen Zustandes; (h) Inhibieren der Antigenpräsentation in einer Zelle; (i) Inhibieren der NF-κB abhängigen induzierbaren Zelladhäsion; oder (j) Inhibieren der HIV-Replikation.
  27. Verwendung gemäß Anspruch 26, worin ein Patient diagnostiziert worden ist mit oder im Risiko steht, einen Zustand zu entwickeln, ausgewählt aus der Gruppe, bestehend aus Gewebsabstoßung, Organabstoßung, Arthritis, einer Infektion, Dermatosen, entzündlichen Darmerkrankungen, Asthma, Osteoporose, Osteoarthritis und einer Autoimmunerkrankung.
DE69530936T 1994-10-28 1995-10-27 Boronsäure-und-esterverbindungen, deren systhese und verwendungen Expired - Lifetime DE69530936T3 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US33052594A 1994-10-28 1994-10-28
US330525 1994-10-28
US08/442,581 US6083903A (en) 1994-10-28 1995-05-16 Boronic ester and acid compounds, synthesis and uses
US442581 1995-05-16
PCT/US1995/014117 WO1996013266A1 (en) 1994-10-28 1995-10-27 Boronic ester and acid compounds, synthesis and uses

Publications (4)

Publication Number Publication Date
DE69530936D1 DE69530936D1 (de) 2003-07-03
DE69530936T2 DE69530936T2 (de) 2004-02-26
DE69530936C5 true DE69530936C5 (de) 2007-02-22
DE69530936T3 DE69530936T3 (de) 2010-08-26

Family

ID=26987313

Family Applications (5)

Application Number Title Priority Date Filing Date
DE69530936T Expired - Lifetime DE69530936T3 (de) 1994-10-28 1995-10-27 Boronsäure-und-esterverbindungen, deren systhese und verwendungen
DE69534727T Expired - Lifetime DE69534727T2 (de) 1994-10-28 1995-10-27 Bor Säure- und Ester-Verbindungen, Synthese und Verwendungen
DE200412000025 Pending DE122004000025I1 (de) 1994-10-28 1995-10-27 Borons{ure-und-Esterverbindungen, deren Systhese und Verwendungen.
DE69535866T Expired - Lifetime DE69535866D1 (de) 1994-10-28 1995-10-27 Bor Säure- und Ester-Verbindungen, Synthese und Verwendungen
DE1995630936 Active DE122004000025I2 (de) 1994-10-28 1995-10-27 Borons{ure-und-esterverbindungen, deren Systhese und Verwendungen

Family Applications After (4)

Application Number Title Priority Date Filing Date
DE69534727T Expired - Lifetime DE69534727T2 (de) 1994-10-28 1995-10-27 Bor Säure- und Ester-Verbindungen, Synthese und Verwendungen
DE200412000025 Pending DE122004000025I1 (de) 1994-10-28 1995-10-27 Borons{ure-und-Esterverbindungen, deren Systhese und Verwendungen.
DE69535866T Expired - Lifetime DE69535866D1 (de) 1994-10-28 1995-10-27 Bor Säure- und Ester-Verbindungen, Synthese und Verwendungen
DE1995630936 Active DE122004000025I2 (de) 1994-10-28 1995-10-27 Borons{ure-und-esterverbindungen, deren Systhese und Verwendungen

Country Status (25)

Country Link
US (16) US6083903A (de)
EP (4) EP1312609B1 (de)
JP (1) JP3717934B2 (de)
KR (1) KR100398944B1 (de)
CN (2) CN101077875B (de)
AT (3) ATE241631T1 (de)
AU (1) AU710564B2 (de)
CA (2) CA2496538C (de)
CH (1) CH0788360H1 (de)
CY (1) CY2484B1 (de)
DE (5) DE69530936T3 (de)
DK (3) DK1627880T3 (de)
ES (3) ES2314540T3 (de)
FI (2) FI114801B (de)
FR (1) FR04C0014I2 (de)
HK (2) HK1002059A1 (de)
IL (5) IL115790A (de)
LU (1) LU91083I2 (de)
MX (1) MX9703063A (de)
NL (1) NL300151I2 (de)
NO (2) NO310558B1 (de)
NZ (2) NZ296717A (de)
PT (3) PT1627880E (de)
TW (1) TW318850B (de)
WO (1) WO1996013266A1 (de)

Families Citing this family (302)

* Cited by examiner, † Cited by third party
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
AU741802B2 (en) 1997-02-15 2001-12-13 Millennium Pharmaceuticals, Inc. Treatment of infarcts through inhibition of NF-kappaB
US6221888B1 (en) * 1997-05-29 2001-04-24 Merck & Co., Inc. Sulfonamides as cell adhesion inhibitors
EP1017398A1 (de) * 1997-09-25 2000-07-12 Proscript, Inc. Proteasome inhibitoren, inhibitoren des ubiquitinweges oder verbindungen, die mit der durch den ubiquitinweg enstehenden nf-kb aktivierung interferieren zur behandlung von entzündlichen und autoimmunerkrankungen
KR100458403B1 (ko) * 1997-09-29 2004-11-26 포인트 써러퓨틱스, 인크. 생체외 조혈세포의 자극방법
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
US6838436B1 (en) * 1998-07-10 2005-01-04 Osteoscreen Inc. Inhibitors of proteasomal activity for stimulating bone growth
US6902721B1 (en) 1998-07-10 2005-06-07 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 (de) * 1998-08-26 2000-03-01 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Bivalente Proteasome Inhibitore
EP1123412B1 (de) * 1998-10-20 2004-10-06 Millennium Pharmaceuticals, Inc. Verfahren zur überwachung der proteasomeinhibitorarzneimitteleffekte
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
CA2419238A1 (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
EP1430903A1 (de) * 2000-10-12 2004-06-23 Viromics Gmbh Verwendung von Proteasome Hemmern zur Behandlung von Virus-Infektionen
TR201819416T4 (tr) * 2001-01-25 2019-01-21 The United States Of America Represented By The Sec Dep Of Health And Human Services Boronik asit bileşiklerinin formülasyonu.
US7112588B2 (en) * 2001-05-21 2006-09-26 Alcon, Inc. Use of proteasome inhibitors to treat dry eye disorders
PL367287A1 (en) 2001-05-21 2005-02-21 Alcon, Inc. Use of proteasome inhibitors to treat dry eye disorders
EP1399468B1 (de) 2001-05-30 2006-02-15 Novartis AG 2-((n-(2-amino-3-(heteroaryl- oder -aryl)propionyl)aminoacyl)amino)-alkylboronsäurederivate
WO2003033507A1 (fr) * 2001-10-12 2003-04-24 Kyorin Pharmaceutical Co., Ltd. Derives d'acide benzylmalonique et inhibiteurs de proteasomes les contenant
WO2003033506A1 (fr) * 2001-10-12 2003-04-24 Kyorin Pharmaceutical Co., Ltd. Derive d'acide d'aminoborane et medicament inhibiteur de proteasomes le contenant
US7524883B2 (en) 2002-01-08 2009-04-28 Eisai R&D Management Co., Ltd. Eponemycin and epoxomicin analogs and uses thereof
EP1487459A4 (de) * 2002-03-12 2006-05-24 Ariad Pharma Inc Peptid-analoga und ihre verwendung
KR20040093692A (ko) * 2002-03-13 2004-11-08 얀센 파마슈티카 엔.브이. 히스톤 디아세틸라제의 신규한 저해제로서의 피페라지닐-,피페리디닐- 및 모르폴리닐-유도체
US7501417B2 (en) 2002-03-13 2009-03-10 Janssen Pharmaceutica, N.V. Aminocarbonyl-derivatives as novel inhibitors of histone deacetylase
CN100503599C (zh) * 2002-03-13 2009-06-24 詹森药业有限公司 作为组蛋白脱乙酰酶的新颖抑制剂的羰基氨基衍生物
JP4725945B2 (ja) 2002-03-13 2011-07-13 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スルホニルアミノ誘導体
ATE481104T1 (de) * 2002-04-05 2010-10-15 Virologik Gmbh Mittel zur behandlung von flaviviridae- infektionen
US7514579B2 (en) * 2002-06-13 2009-04-07 Johns Hopkins University Boronic chalcone derivatives and uses thereof
JP2006506442A (ja) * 2002-07-09 2006-02-23 ポイント セラピューティクス， インコーポレイテッド ボロプロリン化合物併用療法
WO2004016253A1 (en) * 2002-08-14 2004-02-26 Janssen Pharmaceutica N.V. Use of nf-kappa b inhibitors for the treatment of mastitis
US20050282757A1 (en) * 2002-09-09 2005-12-22 Trigen Limited Peptide boronic acid compounds useful in anticoagulation
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
US20060084592A1 (en) * 2002-09-09 2006-04-20 Trigen Limited Peptide boronic acid inhibitors
WO2004022071A1 (en) * 2002-09-09 2004-03-18 Trigen Limited Multivalent metal salts of boronic acids for treating thrombosis
US20050176651A1 (en) * 2002-09-09 2005-08-11 Trigen Limited Peptide boronic acids useful in making salts thereof
WO2004026406A1 (en) * 2002-09-20 2004-04-01 Alcon, Inc. Use of cytokine synthesis inhibitors for the treatment of dry eye disorders
CA2508348C (en) 2002-12-06 2016-07-12 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
US20070110785A1 (en) * 2003-07-03 2007-05-17 Eugene Tedeschi Medical devices with proteasome inhibitors for the treatment of restenosis
US7223745B2 (en) * 2003-08-14 2007-05-29 Cephalon, Inc. Proteasome inhibitors and methods of using the same
US7576206B2 (en) 2003-08-14 2009-08-18 Cephalon, Inc. Proteasome inhibitors and methods of using the same
JP2007513072A (ja) 2003-11-05 2007-05-24 パリンゲン インコーポレーテッド Ｃｄｉｍ結合抗体における増強されたｂ細胞細胞傷害性
US20060052390A1 (en) * 2003-12-24 2006-03-09 Scios, Inc. Treatment of multiple myeloma by p38 MAP kinase and proteasome inhibition
BRPI0507972A (pt) * 2004-02-23 2007-07-24 Tufts College composto ,composição farmacêutica , uso de um composto, método para inibição da atividade proteolìtica de uma enzima de clivagem pós prolina e composição farmacêutica embalada
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
UA90108C2 (uk) 2004-03-30 2010-04-12 Мілленніум Фармасьютікалз, Інк. Способи одержання сполук боронового естеру та кислоти
WO2005105827A2 (en) 2004-04-15 2005-11-10 Proteolix, Inc. Compounds for proteasome enzyme inhibition
US8198270B2 (en) 2004-04-15 2012-06-12 Onyx Therapeutics, Inc. Compounds for proteasome enzyme inhibition
BRPI0510802A (pt) 2004-05-10 2007-11-06 Proteolix Inc compostos para inibição de enzima
EP1765313A2 (de) 2004-06-24 2007-03-28 Novartis Vaccines and Diagnostics, Inc. Verbindungen als immunstimulatoren
ATE553077T1 (de) 2004-07-23 2012-04-15 Nuada Llc Peptidaseinhibitoren
JP4948403B2 (ja) 2004-07-28 2012-06-06 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インヒビターとしての置換インドリルアルキルアミノ誘導体
WO2006045066A2 (en) 2004-10-20 2006-04-27 Proteolix, Inc. Labeled compounds for proteasome inhibition
US8377435B2 (en) 2004-11-05 2013-02-19 The Board Of Trustees Of The Leland Stanford Junior University Antibody induced cell membrane wounding
TW200618820A (en) * 2004-11-05 2006-06-16 Alza Corp Liposome formulations of boronic acid compounds
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
EP1845973B1 (de) 2005-01-21 2015-08-12 Astex Therapeutics Limited Pharmazeutische verbindungen
US20090018146A1 (en) * 2005-01-27 2009-01-15 Research Development Corporation 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
PT1853251E (pt) 2005-02-16 2013-07-19 Anacor Pharmaceuticals Inc Boroftalidas substituídas com halogéneo para o tratamento de infecções
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
EP1885710B1 (de) 2005-05-18 2015-08-19 Janssen Pharmaceutica N.V. Substituierte aminopropenylpiperidin- oder morpholinderivate als neue histondeacetylase-hemmer
AU2006202209B2 (en) * 2005-05-27 2011-04-14 Lifescan, Inc. Amniotic fluid derived cells
WO2006133052A2 (en) * 2005-06-08 2006-12-14 Centocor, Inc. A cellular therapy for ocular degeneration
WO2007002972A2 (en) * 2005-07-06 2007-01-11 Biodevelops Pharma Entwicklung Gmbh Use of a compound for enhancing the expression of membrane proteins on the cell surface
EP1752467A1 (de) 2005-08-10 2007-02-14 4Sc Ag Krebszellen-, t-Zellen- und Keratinocyte-Proliferation-Inhibitoren
US7531517B2 (en) 2005-08-10 2009-05-12 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
JP5436860B2 (ja) 2005-11-09 2014-03-05 オニキス セラピューティクス， インク． 酵素阻害のための化合物
EP1956908A2 (de) * 2005-12-08 2008-08-20 Cytokinetics, Inc. Gewisse zusammensetzungen und behandlungsverfahren
CN105949230A (zh) 2005-12-30 2016-09-21 安纳考尔医药公司 含硼的小分子
EP1979327A1 (de) * 2006-01-19 2008-10-15 Janssen Pharmaceutica, N.V. Pyridin- und pyrimidinderivate als inhibitoren von histondeacetylase
WO2007082882A1 (en) * 2006-01-19 2007-07-26 Janssen Pharmaceutica N.V. Substituted indolyl-alkyl-amino-derivatives as inhibitors of histone deacetylase
SI1981874T1 (sl) * 2006-01-19 2009-10-31 Janssen Pharmaceutica Nv Aminofenilni derivati kot novi inhibitorji histon deacetilaze
ES2396986T3 (es) 2006-01-19 2013-03-01 Janssen Pharmaceutica N.V. Derivados de piridina y pirimidina como inhibidores de histona desacetilasa
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)
SI2719388T1 (sl) 2006-02-16 2019-06-28 Anacor Pharmaceuticals, Inc. Majhne molekule, polnjene z borom, kot učinkovine proti vnetjem
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
US7691852B2 (en) 2006-06-19 2010-04-06 Onyx Therapeutics, Inc. Compounds for enzyme inhibition
AU2007296259A1 (en) * 2006-09-15 2008-03-20 Janssen Pharmaceutica Nv Combinations of class-I specific histone deacetylase inhibitors with proteasome inhibitors
EA020276B1 (ru) * 2006-09-15 2014-10-30 Янссен Фармацевтика Нв Ингибиторы гистоновых дезацетилаз с сочетанной активностью в отношении гистоновых дезацетилаз класса i и класса ii в комбинации с ингибиторами протеасом
EP2073807A1 (de) 2006-10-12 2009-07-01 Astex Therapeutics Limited Pharmazeutische kombinationen
US8916552B2 (en) 2006-10-12 2014-12-23 Astex Therapeutics Limited Pharmaceutical combinations
AU2007221966A1 (en) * 2006-12-08 2008-06-26 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
DK2185693T3 (da) 2007-07-31 2019-09-23 Lifescan Inc Differentiering af humane embryoniske stamceller
SI2170396T1 (sl) 2007-08-03 2017-04-26 Summit (Oxford) Limited Kombinacije zdravil za zdravljenje duchennove mišične distrofije
GB0715087D0 (en) 2007-08-03 2007-09-12 Summit Corp Plc Drug combinations for the treatment of duchenne muscular dystrophy
AU2016253697A1 (en) * 2007-08-06 2016-11-24 Millennium Pharmaceuticals, Inc. Proteasome inhibitors
CN101772507B (zh) * 2007-08-06 2012-12-12 米伦纽姆医药公司 蛋白酶体抑制剂
EA034601B1 (ru) * 2007-08-06 2020-02-25 Милленниум Фармасьютикалз, Инк. Способ получения бороновых кислот
US7442830B1 (en) 2007-08-06 2008-10-28 Millenium Pharmaceuticals, Inc. Proteasome inhibitors
US20100226597A1 (en) * 2007-09-12 2010-09-09 Dr. Reddy's Laboratories Limited Bortezomib and process for producing same
US20090076031A1 (en) * 2007-09-17 2009-03-19 Protia, Llc Deuterium-enriched bortezomib
MY173938A (en) 2007-10-04 2020-02-27 Onyx Therapeutics Inc Crystalline peptide epoxy ketone protease inhibitors and the synthesis of amino acid keto-epoxides
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
CN107574142B (zh) * 2007-11-27 2021-07-06 生命扫描有限公司 人胚胎干细胞的分化
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
UY31545A1 (es) 2007-12-20 2009-08-03 Nuevos derivados de 2-carboxamida cianoaminourea, sus sales y profarmacos farmacéuticamente aceptables, procesos de preparacion y aplicaciones
CA2715878C (en) 2008-02-21 2017-06-13 Centocor Ortho Biotech Inc. Methods, surface modified plates and compositions for cell attachment, cultivation and detachment
KR101672511B1 (ko) * 2008-03-06 2016-11-03 아나코르 파마슈티칼스 인코포레이티드 소염제로써 붕소가 함유된 소분자
WO2009140309A2 (en) * 2008-05-12 2009-11-19 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
EA027346B1 (ru) * 2008-06-17 2017-07-31 Милленниум Фармасьютикалз, Инк. Соединения боронатного эфира и его фармацевтические составы
KR20180018839A (ko) 2008-06-30 2018-02-21 얀센 바이오테크 인코포레이티드 만능 줄기 세포의 분화
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
US20100028307A1 (en) * 2008-07-31 2010-02-04 O'neil John J Pluripotent stem cell differentiation
EP2348863A4 (de) * 2008-09-04 2012-03-07 Anacor Pharmaceuticals Inc Borhaltige kleine moleküle
WO2010028005A1 (en) 2008-09-04 2010-03-11 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
AR075090A1 (es) 2008-09-29 2011-03-09 Millennium Pharm Inc Derivados de acido 1-amino-2-ciclobutiletilboronico inhibidores de proteosoma,utiles como agentes anticancerigenos, y composiciones farmaceuticas que los comprenden.
US9493489B2 (en) * 2008-10-15 2016-11-15 Anacor Pharmaceuticals, Inc. Boron-containing small molecules as anti-protozoal agents
KR20110073584A (ko) 2008-10-21 2011-06-29 오닉스 세라퓨틱스, 인크. 펩티드 에폭시케톤과의 병용 요법
JP2012507289A (ja) * 2008-10-31 2012-03-29 ヤンセン バイオテツク，インコーポレーテツド ヒト胚性幹細胞の膵内分泌系への分化
US9234178B2 (en) 2008-10-31 2016-01-12 Janssen Biotech, Inc. Differentiation of human pluripotent stem cells
EP2366022B1 (de) * 2008-11-20 2016-04-27 Janssen Biotech, Inc. Verfahren und zusammensetzungen zur bindung und kultivierung von zellen auf planaren substraten
MX356756B (es) 2008-11-20 2018-06-11 Centocor Ortho Biotech Inc Células madre pluripotentes en microportadores.
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
KR20110111407A (ko) * 2008-12-17 2011-10-11 아나코르 파마슈티칼스 인코포레이티드 (ｓ)-３-아미노메틸-７-(３-히드록시-프로폭시)-３ｈ-벤조〔ｃ〕〔１,２〕옥사보롤-１-올의 다형태
CA2748921A1 (en) * 2009-01-09 2010-08-12 Sun Pharma Advanced Research Company Limited Bortezumib containing pharmaceutical composition
EP3021120A1 (de) 2009-02-20 2016-05-18 Michael P. Lisanti Verfahren zur diagnose oder prognose eines neoplasmas einschliesslich der bestimmung des expressionsgrads eines proteins in stromazellen neben dem neoplasma
US8536161B2 (en) 2009-03-12 2013-09-17 Genentech, Inc. Combinations of phosphoinositide 3-kinase inhibitor compounds and chemotherapeutic agents for the treatment of hematopoietic malignancies
WO2010106135A1 (en) 2009-03-20 2010-09-23 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Combined use for the treatment of ovarian carcinoma
AR075899A1 (es) 2009-03-20 2011-05-04 Onyx Therapeutics Inc Tripeptidos epoxicetonas cristalinos inhibidores de proteasa
WO2010111361A1 (en) * 2009-03-24 2010-09-30 Janssen Pharmaceutica Nv Biomarkers for assessing peripheral neuropathy response to treatment with a proteasome inhibitor
WO2010114770A1 (en) * 2009-03-30 2010-10-07 Cerulean Pharma Inc. Polymer-agent conjugates, particles, compositions, and related methods of use
CA2756072A1 (en) * 2009-03-30 2010-10-14 Cerulean Pharma Inc. Polymer-agent conjugates, particles, compositions, and related methods of use
WO2010114768A1 (en) * 2009-03-30 2010-10-07 Cerulean Pharma Inc. Polymer-epothilone conjugates, particles, compositions, and related methods of use
MX2011012538A (es) * 2009-05-27 2012-02-08 Cephalon Inc Terapia de combinacion para el tratamiento del mieloma multiple.
CA2765811C (en) 2009-06-19 2018-06-05 Lek Pharmaceuticals D.D. Process for hydrogenation of halogenoalkenes without dehalogenation
EP2270019A1 (de) 2009-06-19 2011-01-05 LEK Pharmaceuticals d.d. Neue synthetische Route zur Herstellung von alpha-Aminoborestern
EP2280016A1 (de) 2009-07-27 2011-02-02 LEK Pharmaceuticals d.d. Neue synthetische Route zur Herstellung von Alpha-Aminoborestern über substituierte Alylene
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
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
JP6219568B2 (ja) 2009-07-20 2017-10-25 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
US8785185B2 (en) 2009-07-20 2014-07-22 Janssen Biotech, Inc. Differentiation of human embryonic stem cells
JP5819825B2 (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
US8343944B2 (en) * 2009-07-28 2013-01-01 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
US20110207701A1 (en) * 2009-08-19 2011-08-25 Anacor Pharmaceuticals, Inc. Boron-containing small molecules as antiprotozoal agents
JP5567136B2 (ja) 2009-09-08 2014-08-06 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト ４−置換ピリジン−３−イル−カルボキサミド化合物及び使用方法
US20110124597A1 (en) * 2009-09-25 2011-05-26 Anacor Pharmaceuticals, Inc. Boron containing small molecules
EP2305285A1 (de) 2009-09-29 2011-04-06 Julius-Maximilians-Universität Würzburg Mittel und Verfahren zur Behandlung von ischämischen Erkrankungen
DK2519231T3 (en) * 2009-10-01 2017-06-26 Janssen Pharmaceutica Nv Proteasome inhibitors for the treatment of cancer
US9346834B2 (en) 2009-10-20 2016-05-24 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
WO2011060179A1 (en) 2009-11-13 2011-05-19 Onyx Therapeutics, Inc Use of peptide epoxyketones for metastasis suppression
EP2516449A1 (de) 2009-12-22 2012-10-31 Cephalon, Inc. Proteasehemmer und verfahren zu ihrer herstellung, reinigung und verwendung
RU2664864C1 (ru) 2009-12-23 2018-08-23 Янссен Байотек, Инк. Способы увеличения экспрессии ngn3 и nkx6.1 в эндокринных клетках поджелудочной железы
MX343786B (es) 2009-12-23 2016-11-22 Janssen Biotech Inc Diferenciacion de celulas madre embrionarias humanas.
WO2011090940A1 (en) 2010-01-19 2011-07-28 Cerulean Pharma Inc. Cyclodextrin-based polymers for therapeutic delivery
US8716478B2 (en) 2010-01-27 2014-05-06 Anacor Pharmaceuticals, Inc. Boron-containing small molecules
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
EP2542238B1 (de) * 2010-03-01 2015-08-12 Onyx Therapeutics, Inc. Verbindungen zur immunproteasomhemmung
EP2547333B1 (de) * 2010-03-18 2017-08-23 Innopharma, Inc. Stabile bortezomibformulierungen
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
EP2550362B1 (de) 2010-03-25 2017-01-04 Oregon Health&Science University Cmv-glycoproteine und rekombinante vektoren
EA029521B1 (ru) 2010-03-31 2018-04-30 Милленниум Фармасьютикалз, Инк. Производные 1-амино-2-циклопропилэтилбороновой кислоты
AU2013204868B2 (en) * 2010-03-31 2016-10-13 Millennium Pharmaceuticals, Inc. Derivatives of 1-amino-2-cyclopropylethylboronic acid
MX2012011604A (es) 2010-04-07 2013-02-27 Onyx Therapeutics Inc Inhibidor de inmunoproteasoma de péptido epoxicetona cristalino.
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
EP2560647B1 (de) 2010-04-19 2016-04-13 Niiki Pharma Inc. Kombinationstherapie mit einem proteasomhemmer und einem galliumkomplex
WO2011139379A2 (en) 2010-05-06 2011-11-10 Duke University A method of treating patients undergoing protein replacement therapy, gene replacement therapy, or other therapeutic modalities
RU2587634C2 (ru) 2010-05-12 2016-06-20 Янссен Байотек, Инк. Дифференцирование эмбриональных стволовых клеток человека
EP2571525A4 (de) 2010-05-18 2016-04-27 Cerulean Pharma Inc Zusammensetzungen und verfahren zur behandlung von autoimmun- und anderen erkrankungen
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
ES2585028T3 (es) 2010-08-31 2016-10-03 Janssen Biotech, Inc. Diferenciación de células madre pluripotentes
KR101851956B1 (ko) 2010-08-31 2018-04-25 얀센 바이오테크 인코포레이티드 인간 배아 줄기 세포의 분화
ES2659393T3 (es) 2010-08-31 2018-03-15 Janssen Biotech, Inc. Diferenciación de células madre embrionarias humanas
BR112013005426B1 (pt) 2010-09-07 2021-08-24 Anacor Pharmaceuticals, Inc Composto, composição, combinação, e, formulação farmacêutica
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
CA2813003A1 (en) 2010-10-05 2012-04-12 Fresenius Kabi Usa, Llc Bortezomib formulations stabilised with boric acid
ES2548256T3 (es) 2010-10-14 2015-10-15 Synthon Bv Proceso para la preparación de bortezomib y los intermedios para el proceso
PT2670753T (pt) 2011-01-31 2017-01-10 Novartis Ag Novos derivados heterocíclicos
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
WO2012133884A1 (ja) 2011-03-31 2012-10-04 ナノキャリア株式会社 ボロン酸化合物を含有したブロック共重合体を含む医薬組成物
EP2691530B1 (de) 2011-06-10 2018-03-07 Oregon Health & Science University Cmv-glycoproteine und rekombinante vektoren
US20140121182A1 (en) * 2011-06-22 2014-05-01 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
ES2586328T3 (es) 2011-08-11 2016-10-13 Janssen Pharmaceutica, N.V. Factores predisponentes para el tratamiento del cáncer
CA2844086A1 (en) 2011-08-19 2013-02-28 Glaxo Group Limited Benzofuran compounds for the treatment of hepatitis c virus infections
CN108383893A (zh) * 2011-08-30 2018-08-10 塔夫茨大学信托人 用于治疗实体瘤的fap-活化的蛋白酶体抑制剂
EP2568289A3 (de) 2011-09-12 2013-04-03 International AIDS Vaccine Initiative Immunselektion von rekombinantem vesikulärem Stomatitisvirus mit Expression von HIV-1-Proteinen durch Breitbandneutralisierungs-Antikörper
US9402894B2 (en) 2011-10-27 2016-08-02 International Aids Vaccine Initiative Viral particles derived from an enveloped virus
ES2776144T3 (es) 2011-10-28 2020-07-29 Millennium Pharm Inc Biomarcadores de respuesta a inhibidores de NAE
EP2771342B1 (de) 2011-10-28 2016-05-18 Novartis AG Purinderivate und ihre verwendung bei der behandlung von krankheiten
CA2855368A1 (en) 2011-11-11 2013-05-16 Millennium Pharmaceuticals, Inc. Biomarkers of response to proteasome inhibitors
CN104039328B (zh) 2011-11-11 2018-10-09 米伦纽姆医药公司 对蛋白酶体抑制剂的反应的生物标记
KR101912978B1 (ko) 2011-11-17 2018-10-29 도꾜 다이가꾸 페닐보론산기가 도입된 블록 공중합체 및 그의 용도
RU2705001C2 (ru) 2011-12-22 2019-11-01 Янссен Байотек, Инк. Дифференцировка эмбриональных стволовых клеток человека в одногормональные инсулинположительные клетки
WO2013110005A1 (en) 2012-01-18 2013-07-25 Wisconsin Alumni Research Foundation Boronate-mediated delivery of molecules into cells
US9732101B2 (en) 2012-01-18 2017-08-15 Wisconsin Alumni Research Foundation Bioreversible boronates for delivery of molecules into cells
WO2013112601A1 (en) 2012-01-24 2013-08-01 Millennium Pharmaceuticals, Inc. Methods of treatment of cancer
GB2523211B (en) 2012-01-27 2020-03-18 Univ Jefferson MCT protein inhibitor-related prognostic and therapeutic methods
MX363819B (es) 2012-02-08 2019-04-03 Igm Biosciences Inc Uniones a cdim y sus usos.
US10293048B2 (en) 2012-03-02 2019-05-21 Dr. Reddy's Laboratories Limited Pharmaceutical compositions comprising boronic acid compounds
CA2866590A1 (en) 2012-03-07 2013-09-12 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
WO2013173283A1 (en) 2012-05-16 2013-11-21 Novartis Ag Dosage regimen for a pi-3 kinase inhibitor
JP6469003B2 (ja) 2012-06-08 2019-02-13 ヤンセン バイオテツク，インコーポレーテツド 膵内分泌細胞へのヒト胚性幹細胞の分化
EP2679596B1 (de) 2012-06-27 2017-04-12 International Aids Vaccine Initiative HIV-1 Env-proteinvariante
EP2869820A4 (de) 2012-07-09 2016-02-17 Onyx Therapeutics Inc Prodrugs von peptidepoxidketonproteaseinhibitoren
JP2013006855A (ja) * 2012-09-03 2013-01-10 Millennium Pharmaceuticals Inc プロテアソーム阻害剤
BR112015005343A2 (pt) * 2012-09-11 2017-07-04 Cipla Ltd processo para a preparação de bortezomib, composto, bortezomib ou seu anidrido, e, processo para a preparação de um composto
CA2886783A1 (en) 2012-10-01 2014-04-10 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
EP2919786A4 (de) 2012-11-16 2016-06-01 Shilpa Medicare Ltd Verfahren für kristallines bortezomib
WO2014097306A1 (en) 2012-12-21 2014-06-26 Natco Pharma Limited Stable and pure polymorphic form of bortezomib
EP2938723B1 (de) 2012-12-31 2023-02-01 Janssen Biotech, Inc. Differenzierung humaner embryonaler stammzellen in endokrine pankreaszellen mithilfe von hb9-regulatoren
US10370644B2 (en) 2012-12-31 2019-08-06 Janssen Biotech, Inc. Method for making human pluripotent suspension cultures and cells derived therefrom
JP6557146B2 (ja) 2012-12-31 2019-08-07 ヤンセン バイオテツク，インコーポレーテツド 多能性幹細胞から膵臓内分泌細胞膵臓内分泌細胞への分化のための、空気−液体界面での、ヒト胚性幹細胞の培養
EP4039798A1 (de) 2012-12-31 2022-08-10 Janssen Biotech, Inc. Aufhängung und gruppierung von menschlichen pluripotenten zellen
KR102194745B1 (ko) 2013-03-13 2020-12-24 포르마 세라퓨틱스 인크. Ｆａｓｎ 억제용 신규 화합물 및 조성물
US10023611B2 (en) 2013-04-16 2018-07-17 Cipla Limited Process for the preparation of bortezomib mannitol ester
WO2014172627A1 (en) 2013-04-19 2014-10-23 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
US10478445B2 (en) 2013-07-03 2019-11-19 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
US10058604B2 (en) 2013-10-07 2018-08-28 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
WO2015076359A1 (ja) * 2013-11-21 2015-05-28 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
PT3076969T (pt) 2013-12-06 2021-11-23 Novartis Ag Regime de dosagem de um inibidor de fosfatidilinositol 3- quinase seletivo para a isoforma alfa
US10167311B2 (en) 2014-02-03 2019-01-01 Ohio State Innovation Foundation Boronic acid esters and pharmaceutical formulations thereof
EP2910557A1 (de) * 2014-02-20 2015-08-26 Ikerchem, S.L. Enantiomerenreine tetrasubstituierte Pyrrolidine als Gerüste für Proteasomhemmer und medizinische Anwendungen davon
US10993960B1 (en) 2014-05-08 2021-05-04 Kawasaki Institute Of Industrial Promotion Pharmaceutical composition
CA2949056A1 (en) 2014-05-16 2015-11-19 Janssen Biotech, Inc. Use of small molecules to enhance mafa expression in pancreatic endocrine cells
UY36132A (es) 2014-05-20 2015-11-30 Millennium Pharm Inc Métodos para terapia de cáncer
EP3177292B1 (de) 2014-08-07 2020-11-25 Mayo Foundation for Medical Education and Research Verbindungen und verwendung zur behandlung von krebs
CN107074885B (zh) * 2014-10-01 2020-11-27 默克专利股份公司 硼酸衍生物
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
EP3069730A3 (de) 2015-03-20 2017-03-15 International Aids Vaccine Initiative Lösliche hiv-1-hüllglykoproteintrimere
US9931394B2 (en) 2015-03-23 2018-04-03 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
CN106478700B (zh) * 2015-08-26 2020-12-29 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
MX2018005298A (es) 2015-11-02 2018-06-22 Novartis Ag Regimen de dosificacion para un inhibidor de fosfatidilinositol 3-quinasa.
EP3389715A4 (de) 2015-12-14 2019-06-12 David K. Thomas Zusammensetzungen und verfahren zur behandlung von kardialer dysfunktion
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
EP3472151A4 (de) 2016-06-21 2020-03-04 Orion Ophthalmology LLC Carbocyclische prolinamidderivate
KR102595723B1 (ko) 2016-06-21 2023-10-27 오리온 옵탈몰로지 엘엘씨 헤테로시클릭 프롤린아미드 유도체
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
WO2018073790A1 (en) 2016-10-20 2018-04-26 Pfizer Inc. Therapeutic particles with peptide boronic acid or boronate ester compounds and methods of making and using same
ES2914123T3 (es) 2017-01-09 2022-06-07 Shuttle Pharmaceuticals Inc Inhibidores selectivos de la histona desacetilasa para el tratamiento de una enfermedad humana
US11584733B2 (en) 2017-01-09 2023-02-21 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
EP3589659A4 (de) 2017-02-28 2021-03-24 Mayo Foundation for Medical Education and Research Verbindungen und verwendung zur behandlung von krebs
CN117338932A (zh) 2017-08-23 2024-01-05 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
WO2019053611A1 (en) 2017-09-14 2019-03-21 Glaxosmithkline Intellectual Property Development Limited POLY THERAPY FOR THE TREATMENT OF 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
ES2928787T3 (es) * 2017-11-16 2022-11-22 Principia Biopharma Inc Inhibidores del inmunoproteasoma
IL274523B2 (en) 2017-11-16 2024-02-01 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
WO2019178438A1 (en) 2018-03-15 2019-09-19 Abbvie Inc. Abbv-621 in combination with anti-cancer agents for the treatment of cancer
US11243207B2 (en) 2018-03-29 2022-02-08 Mayo Foundation For Medical Education And Research Assessing and treating cancer
US10793554B2 (en) 2018-10-29 2020-10-06 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
CN114437119A (zh) * 2020-10-30 2022-05-06 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
US20240016815A1 (en) * 2020-12-02 2024-01-18 Hoffman Technologies Llc 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
US20230062279A1 (en) 2021-08-12 2023-03-02 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
WO2023220641A2 (en) 2022-05-11 2023-11-16 Juno Therapeutics, Inc. Methods and uses related to t cell therapy and production of same
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

Family Cites Families (49)

* Cited by examiner, † Cited by third party
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
US5250720A (en) * 1987-06-05 1993-10-05 The Dupont Merck Pharmaceutical Company Intermediates for preparing 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
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
AU661270B2 (en) 1990-03-05 1995-07-20 Cephalon, Inc. Chymotrypsin-like proteases and their inhibitors
GB9017694D0 (en) * 1990-08-13 1990-09-26 Sandoz Ltd Improvements in or relating to organic chemistry
EP0478050A1 (de) * 1990-09-24 1992-04-01 Unilever N.V. Detergentzusammensetzung
GB9024129D0 (en) * 1990-11-06 1990-12-19 Thrombosis Research Trust Inhibitors and substrates of thrombin
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
JPH06504061A (ja) * 1990-12-28 1994-05-12 コーテックス　ファーマシューティカルズ　インコーポレイテッド 神経変性の治療および予防におけるカルパイン阻害剤の使用
EP0564561A4 (en) * 1990-12-28 1994-08-10 Georgia Tech Res Inst Peptides ketoamides, ketoacids, and ketoesters
AU666660B2 (en) * 1991-04-30 1996-02-22 Procter & Gamble Company, The Built liquid detergents with boric-polyol complex to inhibit proteolytic enzyme
EP0511456A1 (de) * 1991-04-30 1992-11-04 The Procter & Gamble Company Flüssiges Reinigungsmittel mit einem aromatischen Boratester zur Inhibierung des proteolytischen Enzyms
JPH06507198A (ja) * 1991-04-30 1994-08-11 ザ、プロクター、エンド、ギャンブル、カンパニー アリールボロン酸を含有する液体洗浄剤
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
DE69314169T2 (de) * 1992-04-16 1998-01-15 Zeneca Ltd Peptide mit eine alphaaminoboronaire gruppe and ihre verwendung als elastasehemmer
EP0583536B1 (de) 1992-08-14 1997-03-05 The Procter & Gamble Company Alpha-aminoborsäurehaltige flüssige Waschmittel
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
US5550262A (en) * 1994-11-14 1996-08-27 Cephalon, Inc. Multicatalytic protease inhibitors
US5614649A (en) 1994-11-14 1997-03-25 Cephalon, Inc. Multicatalytic protease inhibitors
TR201819416T4 (tr) * 2001-01-25 2019-01-21 The United States Of America Represented By The Sec Dep Of Health And Human Services Boronik asit bileşiklerinin formülasyonu.
UA90108C2 (uk) * 2004-03-30 2010-04-12 Мілленніум Фармасьютікалз, Інк. Способи одержання сполук боронового естеру та кислоти

Also Published As

Publication number Publication date
IL137726A (en) 2004-08-31
PT1312609E (pt) 2006-05-31
US20090247731A1 (en) 2009-10-01
DE69530936T2 (de) 2004-02-26
DK1312609T3 (da) 2006-05-15
US7119080B2 (en) 2006-10-10
US20070282100A1 (en) 2007-12-06
CA2496538A1 (en) 1996-05-09
FI120974B (fi) 2010-05-31
EP1312609B1 (de) 2005-12-28
PT788360E (pt) 2003-10-31
DE69535866D1 (de) 2008-11-27
AU710564C (en) 1996-05-23
CA2203936A1 (en) 1996-05-09
KR100398944B1 (ko) 2004-06-04
DE69530936D1 (de) 2003-07-03
WO1996013266A1 (en) 1996-05-09
NZ296717A (en) 1999-11-29
HK1002059A1 (en) 1998-07-31
IL133831A0 (en) 2001-04-30
CY2484B1 (en) 2005-06-03
AU4139896A (en) 1996-05-23
EP1627880A1 (de) 2006-02-22
CA2496538C (en) 2011-08-02
EP0788360B3 (de) 2009-08-12
ES2254803T3 (es) 2006-06-16
NO2004004I2 (no) 2007-09-10
NL300151I1 (nl) 2004-08-02
US6747150B2 (en) 2004-06-08
US20080132678A1 (en) 2008-06-05
US20020173488A1 (en) 2002-11-21
NO971929L (no) 1997-06-12
EP1312609A1 (de) 2003-05-21
DE122004000025I2 (de) 2006-09-07
US8003791B2 (en) 2011-08-23
TW318850B (de) 1997-11-01
FI20041415A (fi) 2004-11-03
IL137726A0 (en) 2001-10-31
KR970706824A (ko) 1997-12-01
DK1627880T3 (da) 2008-12-08
DK0788360T3 (da) 2003-09-22
US20060122390A1 (en) 2006-06-08
DE122004000025I1 (de) 2004-09-30
AU710564B2 (en) 1999-09-23
US20130310320A1 (en) 2013-11-21
US8378099B2 (en) 2013-02-19
US6066730A (en) 2000-05-23
IL115790A (en) 2002-12-01
NO2004004I1 (no) 2004-08-06
CH0788360H1 (de) 2006-03-15
DE69534727T2 (de) 2006-09-14
EP0788360B1 (de) 2003-05-28
US6465433B1 (en) 2002-10-15
US20110306560A1 (en) 2011-12-15
FR04C0014I2 (de) 2005-05-21
EP1997823A1 (de) 2008-12-03
US7531526B2 (en) 2009-05-12
CN1305475C (zh) 2007-03-21
US20030199561A1 (en) 2003-10-23
ES2314540T3 (es) 2009-03-16
JPH10510245A (ja) 1998-10-06
FI971746A0 (fi) 1997-04-23
EP1627880B1 (de) 2008-10-15
LU91083I9 (de) 2018-12-28
DE69530936T3 (de) 2010-08-26
LU91083I2 (fr) 2004-08-09
CA2203936C (en) 2005-04-12
HK1087714A1 (en) 2006-10-20
PT1627880E (pt) 2009-01-23
ATE314378T1 (de) 2006-01-15
FI114801B (fi) 2004-12-31
DK0788360T5 (da) 2017-09-18
FI971746A (fi) 1997-06-06
JP3717934B2 (ja) 2005-11-16
US6297217B1 (en) 2001-10-02
ATE241631T1 (de) 2003-06-15
FR04C0014I1 (de) 2004-09-17
NO310558B1 (no) 2001-07-23
EP0788360A4 (de) 1998-05-06
US20040167332A1 (en) 2004-08-26
ES2199257T7 (es) 2010-03-31
IL133831A (en) 2004-03-28
NL300151I2 (nl) 2004-09-01
US20150072942A1 (en) 2015-03-12
MX9703063A (es) 1998-07-31
US5780454A (en) 1998-07-14
NO971929D0 (no) 1997-04-25
ATE411324T1 (de) 2008-10-15
CN1168633A (zh) 1997-12-24
US6617317B1 (en) 2003-09-09
NZ337211A (en) 2000-12-22
IL115790A0 (en) 1996-01-19
DE69534727D1 (de) 2006-02-02
ES2199257T3 (es) 2004-02-16
EP0788360A1 (de) 1997-08-13
CN101077875A (zh) 2007-11-28
CN101077875B (zh) 2011-01-26
US6548668B2 (en) 2003-04-15
US6083903A (en) 2000-07-04

Similar Documents

Publication Publication Date Title
DE69530936C5 (de) Boronsäure-und-esterverbindungen, deren systhese und verwendungen
DE69826267T2 (de) Haarwuchszusammensetzungen und deren verwendungen
DE10199023I1 (de) Benzoenaphthalinderivate Verfahren zu deren Herstellung und ihre Verwendung in Pharmazie und Kosmetik
JP5023135B2 (ja) 皮膚外用剤
DE2607592A1 (de) Acetylenderivate von aminosaeuren sowie verfahren zu deren herstellung
DE3415413A1 (de) Melanin-inhibitor
JPH11279040A (ja) 皮膚外用剤
DE69837564T2 (de) Azaheterozyklische derivate zur behandlung von haarausfall und neurologischer krankheiten
DE2854308A1 (de) Anticholinergische substanzen mit antisekretorischer wirkung, ihre herstellung und verwendung
DE3141586A1 (de) 1,8-dihydroxy-9-anthron-derivate, verfahren zu ihrer herstellung und ihre verwendung in der pharmazie und kosmetik
JPS6126996B2 (de)
JP4070357B2 (ja) 皮膚外用剤
EP0025218A1 (de) Pharmakologisch aktive Peptide und diese enthaltende Arzneimittel
DE3122784A1 (de) "n(pfeil hoch)6(pfeil hoch)-substituierte adenosine, verfahren zu deren herstellung sowie dieselben enthaltende pharmazeutische praeparate"
JP3657068B2 (ja) 光老化防止改善剤および皮膚外用剤
DE2600325A1 (de) Butazonderivate, verfahren zu deren herstellung und sie enthaltende arzneimittel
JPH08501808A (ja) ラジカルの捕獲に使用可能な新規ニトロン
DE2615129C3 (de) Tripeptide, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Zubereitungen
DE2320945A1 (de) Neue ester der acetylsalicylsaeure
DE2702535A1 (de) Neue cysteinderivate, ihre herstellung und verwendung
JP2001172197A (ja) 皮膚外用剤
DE2611162C2 (de)
SU694497A1 (ru) 1-Адамантиламмоний -хлорэтилоксоминат, про вл ющий адреноблокирующую активность
DE3431195A1 (de) Neue benzodiazepine, verfahren zu ihrer herstellung sowie ihre verwendung
DE3521074A1 (de) 10-aryl-1,8-dihydroxyanthrone, ihre ester, verfahren zu ihrer herstellung und ihre verwendung in der human- oder veterinaermedizin sowie als kosmetikum

Legal Events

Date Code Title Description
R040 Withdrawal/refusal of revocation action now final

Free format text: PRODUCT NAME: BORTEZOMIB ODER PHARMAZEUTISCH ANNEHMBARE ESTER DAVON, WAHLWEISE IN DER FORM EINES PHARMAZEUTISCH ANNEHMBAREN SALZES DAVON; REGISTRATION NO/DATE: EU/1/04/274/001 20040426

Spc suppl protection certif: 122004000025

Filing date: 20040622

Expiry date: 20151028

Extension date: 20190428