CA2252465C - Urea derivatives as inhibitors of impdh enzyme - Google Patents

Urea derivatives as inhibitors of impdh enzyme Download PDF

Info

Publication number
CA2252465C
CA2252465C CA002252465A CA2252465A CA2252465C CA 2252465 C CA2252465 C CA 2252465C CA 002252465 A CA002252465 A CA 002252465A CA 2252465 A CA2252465 A CA 2252465A CA 2252465 C CA2252465 C CA 2252465C
Authority
CA
Canada
Prior art keywords
substituents
alkyl
nr6c
agent
present
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 - Fee Related
Application number
CA002252465A
Other languages
English (en)
French (fr)
Other versions
CA2252465A1 (en
Inventor
David M. Armistead
Michael C. Badia
Guy W. Bemis
Randy S. Bethiel
Catharine A. Frank
Perry M. Novak
Steven M. Ronkin
Jeffrey O. Saunders
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.)
Vertex Pharmaceuticals Inc
Original Assignee
Vertex 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
Priority claimed from US08/636,361 external-priority patent/US5807876A/en
Priority claimed from US08/832,165 external-priority patent/US6054472A/en
Application filed by Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc
Publication of CA2252465A1 publication Critical patent/CA2252465A1/en
Application granted granted Critical
Publication of CA2252465C publication Critical patent/CA2252465C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • 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
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • 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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Vascular Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Enzymes And Modification Thereof (AREA)
CA002252465A 1996-04-23 1997-04-21 Urea derivatives as inhibitors of impdh enzyme Expired - Fee Related CA2252465C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US08/636,361 1996-04-23
US08/636,361 US5807876A (en) 1996-04-23 1996-04-23 Inhibitors of IMPDH enzyme
US08/801,780 1997-02-14
US08/801,780 US6344465B1 (en) 1996-04-23 1997-02-14 Inhibitors of IMPDH enzyme
US08/832,165 US6054472A (en) 1996-04-23 1997-04-02 Inhibitors of IMPDH enzyme
US08/832,165 1997-04-02
PCT/US1997/006623 WO1997040028A1 (en) 1996-04-23 1997-04-21 Urea derivatives as inhibitors of impdh enzyme

Publications (2)

Publication Number Publication Date
CA2252465A1 CA2252465A1 (en) 1997-10-30
CA2252465C true CA2252465C (en) 2007-07-03

Family

ID=27417590

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002252465A Expired - Fee Related CA2252465C (en) 1996-04-23 1997-04-21 Urea derivatives as inhibitors of impdh enzyme

Country Status (21)

Country Link
US (3) US6541496B1 (instruction)
EP (1) EP0902782A1 (instruction)
CN (2) CN1116288C (instruction)
AP (1) AP813A (instruction)
AU (1) AU723730B2 (instruction)
BG (1) BG64507B1 (instruction)
BR (1) BR9708735A (instruction)
CA (1) CA2252465C (instruction)
CZ (1) CZ298463B6 (instruction)
EA (1) EA004771B1 (instruction)
HU (1) HUP0004421A3 (instruction)
ID (1) ID16664A (instruction)
IL (1) IL126674A (instruction)
IN (1) IN190508B (instruction)
NO (1) NO312963B1 (instruction)
NZ (1) NZ332405A (instruction)
OA (1) OA10902A (instruction)
PL (1) PL192628B1 (instruction)
SK (1) SK286662B6 (instruction)
TR (1) TR199802136T2 (instruction)
WO (1) WO1997040028A1 (instruction)

Families Citing this family (159)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69709671T2 (de) * 1996-10-18 2002-08-22 Vertex Pharmaceuticals Inc., Cambridge Inhibitoren von serinproteasen, insbesondere von ns3-protease des hepatitis-c-virus
WO1998024785A1 (en) * 1996-12-02 1998-06-11 Fujisawa Pharmaceutical Co., Ltd. Indole-urea derivatives with 5-ht antagonist properties
EP1366766A1 (en) * 1997-03-14 2003-12-03 Vertex Pharmaceuticals Incorporated Inhibitors of IMPDH enzyme
US6093742A (en) * 1997-06-27 2000-07-25 Vertex Pharmaceuticals, Inc. Inhibitors of p38
JP4555468B2 (ja) * 1997-10-31 2010-09-29 アベンテイス・フアルマ・リミテツド 置換アニリド
WO1999032106A1 (en) * 1997-12-22 1999-07-01 Bayer Corporation Inhibition of raf kinase using substituted heterocyclic ureas
US7329670B1 (en) 1997-12-22 2008-02-12 Bayer Pharmaceuticals Corporation Inhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas
DK1043995T3 (da) * 1997-12-22 2007-03-05 Bayer Pharmaceuticals Corp Inhibering af p38 kinaseaktivitet ved anvendelse af aryl- og heteroaryl-substituerede, heterocykliske urinstoffer
US7517880B2 (en) 1997-12-22 2009-04-14 Bayer Pharmaceuticals Corporation Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
EP1076641A1 (en) * 1998-04-29 2001-02-21 Vertex Pharmaceuticals Incorporated Inhibitors of impdh enzyme
DE69915472T2 (de) * 1998-06-04 2004-08-19 Kumiai Chemical Industry Co., Ltd. Phenylacetylenderivate und bakterizide für landwirtschaft und gartenbau
EP1514867A3 (en) * 1998-10-22 2005-03-23 NeuroSearch A/S Substituted phenyl derivatives, their preparation and use
AU764479B2 (en) 1998-10-29 2003-08-21 Bristol-Myers Squibb Company Compounds derived from an amine nucleus that are inhibitors of IMPDH enzyme
WO2000026197A1 (en) * 1998-10-29 2000-05-11 Bristol-Myers Squibb Company Novel inhibitors of impdh enzyme
US6420403B1 (en) 1998-10-29 2002-07-16 Edwin J. Iwanowicz Inhibitors of IMPDH enzyme
US6596747B2 (en) 1998-10-29 2003-07-22 Bristol-Myers Squibb Company Compounds derived from an amine nucleus and pharmaceutical compositions comprising same
GB9823873D0 (en) 1998-10-30 1998-12-30 Pharmacia & Upjohn Spa 2-ureido-thiazole derivatives,process for their preparation,and their use as antitumour agents
RU2233269C2 (ru) * 1998-11-02 2004-07-27 Авентис Фарма Лимитед Замещенные анилиды, фармацевтическая композиция и способ лечения
TR200101597T2 (tr) * 1998-12-09 2001-10-22 American Home Products Corporation Herpes virüslerinin tiüre önleyicileri.
US6201013B1 (en) 1998-12-09 2001-03-13 American Home Products Corporation Heterocyclic carboxamide-containing thiourea inhibitors of herpes viruses containing a substituted phenylenediamine group
US6166028A (en) 1998-12-09 2000-12-26 American Home Products Corporation Diaminopuridine-containing thiourea inhibitors of herpes viruses
ES2221470T3 (es) * 1998-12-09 2004-12-16 Wyeth Inhibidores de virus herpes derivados de alfa-metilbencil-tiourea que contienen un grupo fenilenodiamina.
US6262090B1 (en) 1998-12-09 2001-07-17 American Home Products Corporation Aminopyridine-containing thiourea inhibitors of herpes viruses
US6337338B1 (en) 1998-12-15 2002-01-08 Telik, Inc. Heteroaryl-aryl ureas as IGF-1 receptor antagonists
CN1337941A (zh) * 1998-12-22 2002-02-27 三菱化学株式会社 酰胺衍生物
IL144144A0 (en) 1999-01-13 2002-05-23 Bayer Ag Omega-carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors
ME00275B (me) 1999-01-13 2011-02-10 Bayer Corp ω-KARBOKSIARIL SUPSTITUISANI DIFENIL KARBAMIDI KAO INHIBITORI RAF KINAZE
US7928239B2 (en) 1999-01-13 2011-04-19 Bayer Healthcare Llc Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
WO2000042012A1 (en) 1999-01-13 2000-07-20 Bayer Corporation φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS
HK1043127B (zh) * 1999-03-12 2004-12-24 贝林格尔‧英格海姆药物公司 作为消炎剂的化合物
CN1196687C (zh) * 1999-03-19 2005-04-13 沃泰克斯药物股份有限公司 Impdh酶抑制剂
US6653309B1 (en) 1999-04-26 2003-11-25 Vertex Pharmaceuticals Incorporated Inhibitors of IMPDH enzyme technical field of the invention
WO2000073288A1 (en) * 1999-05-28 2000-12-07 Vertex Pharmaceuticals Incorporated Method for preparing 5-substituted oxazoles
US6107052A (en) * 1999-06-09 2000-08-22 Roche Diagnostics Corporation Enzymatic measurement of mycophenolic acid
MXPA02000294A (es) * 1999-06-25 2002-06-21 Vertex Pharma Profarmacos de carbamatos inhibidores de impdh.
JP2001011060A (ja) * 1999-06-28 2001-01-16 Nippon Synthetic Chem Ind Co Ltd:The 新規オキサゾール化合物及びその製造方法
JP2001011059A (ja) * 1999-06-28 2001-01-16 Nippon Synthetic Chem Ind Co Ltd:The ５−（２−置換−４−ニトロフェニル）−オキサゾールの製造方法
TWI262185B (en) * 1999-10-01 2006-09-21 Eisai Co Ltd Carboxylic acid derivatives having anti-hyperglycemia and anti-hyperlipemia action, and pharmaceutical composition containing the derivatives
US6867299B2 (en) 2000-02-24 2005-03-15 Hoffmann-La Roche Inc. Oxamide IMPDH inhibitors
AU5553801A (en) 2000-04-24 2001-11-07 Bristol Myers Squibb Co Heterocycles that are inhibitors of impdh enzyme
SV2003000617A (es) 2000-08-31 2003-01-13 Lilly Co Eli Inhibidores de la proteasa peptidomimetica ref. x-14912m
US6423849B1 (en) * 2000-09-01 2002-07-23 The Nippon Synthetic Chemical Industry Co., Ltd. Process of preparing 5-(2-substituted-4-nitrophenyl)-oxazole, novel oxazole compound, and process of preparing the same
US7235576B1 (en) 2001-01-12 2007-06-26 Bayer Pharmaceuticals Corporation Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7371763B2 (en) 2001-04-20 2008-05-13 Bayer Pharmaceuticals Corporation Inhibition of raf kinase using quinolyl, isoquinolyl or pyridyl ureas
US6593362B2 (en) * 2001-05-21 2003-07-15 Guilford Pharmaceuticals Inc. Non-peptidic cyclophilin binding compounds and their use
TW200301698A (en) 2001-12-21 2003-07-16 Bristol Myers Squibb Co Acridone inhibitors of IMPDH enzyme
EP1478358B1 (en) 2002-02-11 2013-07-03 Bayer HealthCare LLC Sorafenib tosylate for the treatment of diseases characterized by abnormal angiogenesis
ATE529406T1 (de) 2002-02-11 2011-11-15 Bayer Healthcare Llc Aryl-harnstoffe als kinase inhibitoren
EP1402887A1 (en) * 2002-09-18 2004-03-31 Jerini AG New compounds for the inhibition of undesired cell proliferation and use thereof
CA2510006C (en) * 2002-12-06 2012-02-07 Vertex Pharmaceuticals Incorporated Compositions comprising a combination of diphenyl urea impdh inhibitors and apoptosis-inducing anti-cancer agents
DE60331367D1 (de) 2002-12-30 2010-04-01 Angiotech Int Ag Wirkstofffreisetzung von schnell gelierender polymerzusammensetzung
US7220768B2 (en) * 2003-02-11 2007-05-22 Wyeth Holdings Corp. Isoxazole-containing thiourea inhibitors useful for treatment of varicella zoster virus
US8796250B2 (en) 2003-05-20 2014-08-05 Bayer Healthcare Llc Diaryl ureas for diseases mediated by PDGFR
DE602004010407T2 (de) 2003-07-23 2008-10-16 Bayer Pharmaceuticals Corp., West Haven Fluorsubstituierter omega-carboxyaryldiphenylharnstoff zur behandlung und prävention von krankheiten und leiden
TWI359147B (en) 2003-09-05 2012-03-01 Vertex Pharma Inhibitors of serine proteases, particularly hcv n
CN101857631A (zh) 2003-10-10 2010-10-13 沃泰克斯药物股份有限公司 丝氨酸蛋白酶、特别是hcv ns3-ns4a蛋白酶的抑制剂
AR045870A1 (es) * 2003-10-11 2005-11-16 Vertex Pharma Terapia de combinacion para la infeccion de virus de hepatitis c
JP4890254B2 (ja) 2003-10-27 2012-03-07 バーテックス ファーマシューティカルズ インコーポレイテッド Ｈｃｖｎｓ３−ｎｓ４ａプロテアーゼ耐性突然変異体
EP1944042A1 (en) 2003-10-27 2008-07-16 Vertex Pharmceuticals Incorporated Combinations for HCV treatment
CA2554999A1 (en) 2004-02-04 2005-08-25 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases, particularly hcv ns3-ns4a protease
US7317030B2 (en) 2004-02-26 2008-01-08 4Sc Ag Compounds as inhibitors of cell proliferation and viral infections
EP1568696A1 (en) * 2004-02-26 2005-08-31 4Sc Ag Compounds as inhibitors of cell proliferation and viral infections
US20110104186A1 (en) 2004-06-24 2011-05-05 Nicholas Valiante Small molecule immunopotentiators and assays for their detection
ES2314690T3 (es) 2004-08-12 2009-03-16 Pfizer, Inc. Derivados de triazolopiridinilsulfanilo como inhibidores de la map quinasa p38.
SG155967A1 (en) * 2004-10-01 2009-10-29 Vertex Pharma Hcv ns3-ns4a protease inhibition
TWI437990B (zh) 2004-10-29 2014-05-21 Vertex Pharma Vx-950之醫藥用途
CN102267978A (zh) * 2005-01-14 2011-12-07 Cgi药学股份有限公司 作为激酶活性调节剂的1,3-二芳基取代的脲
US7625931B2 (en) * 2005-01-14 2009-12-01 Cgi Pharmaceuticals, Inc. Certain substituted diphenyl ureas, as modulators of kinase activity
US20060235009A1 (en) * 2005-02-08 2006-10-19 Richard Glickman Treatment of vascular, autoimmune and inflammatory diseases using low dosages of IMPDH inhibitors
EP1917010A2 (en) * 2005-02-08 2008-05-07 Aspreva Pharmaceuticals SA Compositions and methods for treating vascular, autoimmune and inflammatory diseases
AU2006222365B2 (en) 2005-03-07 2011-07-14 Bayer Healthcare Llc Pharmaceutical composition comprising an omega- carboxyaryl substituted diphenyl urea for the treatment of cancer
US7777040B2 (en) * 2005-05-03 2010-08-17 Cgi Pharmaceuticals, Inc. Certain substituted ureas, as modulators of kinase activity
EP1891062A2 (en) * 2005-05-09 2008-02-27 Vertex Pharmaceuticals, Inc. Polymorphic forms of (s)- tetrahydrofuran-3-yl-3-(3-(3-methoxy-4-(oxazol-5-yl) phenyl) ureido) benzylcarbamate
CN101175718A (zh) 2005-05-09 2008-05-07 沃泰克斯药物股份有限公司 制备联芳基脲及其类似物的方法
EP1912996B1 (en) 2005-07-29 2012-06-20 Janssen R&D Ireland Macrocyclic inhibitors of hepatitis c virus
JP5171624B2 (ja) 2005-07-29 2013-03-27 テイボテク・フアーマシユーチカルズ Ｃ型肝炎ウイルスの大環状阻害剤
CN101273028B (zh) 2005-07-29 2013-08-21 泰博特克药品有限公司 丙型肝炎病毒的大环抑制剂
SI1919898T1 (sl) 2005-07-29 2011-05-31 Tibotec Pharm Ltd Makrociklični inhibitorji virusa hepatitisa C
JO2768B1 (en) 2005-07-29 2014-03-15 تيبوتيك فارماسيوتيكالز ليمتد Large cyclic inhibitors of hepatitis C virus
PE20070210A1 (es) 2005-07-29 2007-04-16 Tibotec Pharm Ltd Compuestos macrociclicos como inhibidores del virus de hepatitis c
AR057704A1 (es) 2005-07-29 2007-12-12 Tibotec Pharm Ltd Inhibidores macrociclicos del virus de la hepatitis c, composicion farmaceutica y proceso de preparacion del compuesto
HRP20110885T1 (hr) 2005-07-29 2011-12-31 Tibotec Pharmaceuticals Makrociklički inhibitori virusa hepatitisa c
PE20070211A1 (es) 2005-07-29 2007-05-12 Medivir Ab Compuestos macrociclicos como inhibidores del virus de hepatitis c
EP2402331A1 (en) * 2005-08-02 2012-01-04 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases
US7964624B1 (en) * 2005-08-26 2011-06-21 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases
AR055395A1 (es) * 2005-08-26 2007-08-22 Vertex Pharma Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c
US7705138B2 (en) 2005-11-11 2010-04-27 Vertex Pharmaceuticals Incorporated Hepatitis C virus variants
EP2392589A3 (en) 2005-11-11 2012-06-20 Vertex Pharmaceuticals Incorporated Hepatitis C virus variants
WO2007098270A2 (en) 2006-02-27 2007-08-30 Vertex Pharmaceuticals Incorporated Co-crystals comprising vx-950 and pharmaceutical compositions comprising the same
NZ571280A (en) 2006-03-16 2011-10-28 Vertex Pharma Deuterated hepatitis C protease inhibitors
US7825152B2 (en) 2006-04-11 2010-11-02 Novartis Ag Organic compounds and their uses
EP2066642A1 (en) * 2006-09-25 2009-06-10 Arete Therapeutics, INC. Soluble epoxide hydrolase inhibitors
JP5616063B2 (ja) 2006-10-04 2014-10-29 ヤンセン・アールアンドデイ・アイルランド Ｈｃｖ阻害剤として有用なカルボキシアミド４−［（４−ピリジル）アミノ］ピリミジン
EA200970493A1 (ru) 2006-11-17 2009-10-30 Тиботек Фармасьютикалз Лтд. Макроциклические ингибиторы вируса гепатита с
CN101687856A (zh) * 2007-02-27 2010-03-31 弗特克斯药品有限公司 共晶体和包含该共晶体的药物组合物
US8575208B2 (en) * 2007-02-27 2013-11-05 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases
AU2008242720A1 (en) * 2007-04-20 2008-10-30 Deciphera Pharmaceuticals, Llc Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases
AU2008248116A1 (en) 2007-05-04 2008-11-13 Vertex Pharmaceuticals Incorporated Combination therapy for the treatment of HCV infection
CN101835774B (zh) * 2007-08-30 2014-09-17 弗特克斯药品有限公司 共晶体和包含该共晶体的药物组合物
PT2238142E (pt) 2007-12-24 2012-09-24 Janssen R & D Ireland Indoles macrocíclicos como inibidores do vírus da hepatite c
TWI454476B (zh) 2008-07-08 2014-10-01 Tibotec Pharm Ltd 用作ｃ型肝炎病毒抑制劑之巨環吲哚衍生物
CN102124012B (zh) 2008-08-14 2014-07-02 泰博特克药品公司 可作为丙型肝炎病毒抑制剂的大环吲哚衍生物
BRPI0922364A2 (pt) 2008-12-03 2017-08-29 Presidio Pharmaceuticals Inc Composto, composição farmacêutica e uso de um composto
WO2010065674A1 (en) 2008-12-03 2010-06-10 Presidio Pharmaceuticals, Inc. Inhibitors of hcv ns5a
EP2396028A2 (en) 2009-02-12 2011-12-21 Vertex Pharmceuticals Incorporated Hcv combination therapies comprising pegylated interferon, ribavirin and telaprevir
US8969342B2 (en) 2009-03-20 2015-03-03 Brandeis University Compounds and methods for treating mammalian gastrointestinal microbial infections
AU2010229795A1 (en) 2009-03-27 2011-10-13 Presidio Pharmaceuticals, Inc. Fused ring inhibitors of hepatitis C
US8512690B2 (en) 2009-04-10 2013-08-20 Novartis Ag Derivatised proline containing peptide compounds as protease inhibitors
US20110182850A1 (en) 2009-04-10 2011-07-28 Trixi Brandl Organic compounds and their uses
WO2011014882A1 (en) 2009-07-31 2011-02-03 Medtronic, Inc. CONTINUOUS SUBCUTANEOUS ADMINISTRATION OF INTERFERON-α TO HEPATITIS C INFECTED PATIENTS
UA108211C2 (uk) 2009-11-04 2015-04-10 Янссен Рід Айрленд Бензімідазолімідазольні похідні
AU2011210795A1 (en) 2010-01-29 2012-08-02 Vertex Pharmaceuticals Incorporated Therapies for treating Hepatitis C virus infection
WO2011112516A1 (en) 2010-03-08 2011-09-15 Ico Therapeutics Inc. Treating and preventing hepatitis c virus infection using c-raf kinase antisense oligonucleotides
CA2800509A1 (en) 2010-05-24 2011-12-01 Presidio Pharmaceuticals, Inc. Inhibitors of hcv ns5a
EP2575818A4 (en) 2010-06-03 2013-11-06 Pharmacyclics Inc USE OF BRUTON TYROSINE KINASE INHIBITORS (BTK)
WO2011156545A1 (en) 2010-06-09 2011-12-15 Vertex Pharmaceuticals Incorporated Viral dynamic model for hcv combination therapy
MX2012015198A (es) 2010-06-24 2013-02-11 Janssen R & D Ireland Preparacion de acido 13-ciclohexil-3-metoxi-6-[metil-(2-{2-[metil- (sulfamoil)-amino]-etoxi}-etil)-carbomoil]-7h-indolo-[2,1-a]-[2]- benzazepin-10-carboxilico.
EP2593105A1 (en) 2010-07-14 2013-05-22 Vertex Pharmaceuticals Incorporated Palatable pharmaceutical composition comprising vx-950
WO2012020036A1 (en) 2010-08-13 2012-02-16 F. Hoffmann-La Roche Ag Hepatitis c virus inhibitors
WO2012109646A1 (en) 2011-02-11 2012-08-16 Vertex Pharmaceuticals Incorporated Treatment of hcv in hiv infection patients
CN102985104A (zh) 2011-02-25 2013-03-20 麦德托尼克公司 在干扰素-α治疗方案中使用药代动力学分布和药效动力学分布的方法和系统
WO2012123298A1 (en) 2011-03-11 2012-09-20 F. Hoffmann-La Roche Ag Antiviral compounds
BR112013032188A2 (pt) 2011-06-23 2016-12-20 Digna Biotech Sl composição, produto e método para tratar pacientes com hepatite c crônica
WO2012175581A1 (en) 2011-06-24 2012-12-27 F. Hoffmann-La Roche Ag Antiviral compounds
HK1199454A1 (en) 2011-10-10 2015-07-03 F. Hoffmann-La Roche Ag Antiviral compounds
CN103987723B (zh) 2011-12-16 2017-03-01 弗·哈夫曼-拉罗切有限公司 Hcv ns5a 的抑制剂
CA2856179C (en) 2011-12-20 2017-02-28 F. Hoffmann-La Roche Ag 2',4'-difluoro-2'-methyl substituted nucleoside derivatives as inhibitors of hcv rna replication
PT2794628T (pt) 2011-12-20 2017-07-05 Riboscience Llc Derivados nucleosídicos 4¿-azido-3¿-fluoro substituídos como inibidores de replicação de arn de vhc
AU2012360905B2 (en) 2011-12-28 2017-04-27 Janssen Sciences Ireland Uc Hetero-bicyclic derivatives as HCV inhibitors
US20130195797A1 (en) 2012-01-31 2013-08-01 Vertex Pharmaceuticals Incorporated High potency formulations of vx-950
CN104185624B (zh) 2012-02-24 2016-10-12 弗·哈夫曼-拉罗切有限公司 抗病毒化合物
US8461179B1 (en) 2012-06-07 2013-06-11 Deciphera Pharmaceuticals, Llc Dihydronaphthyridines and related compounds useful as kinase inhibitors for the treatment of proliferative diseases
US20140010783A1 (en) 2012-07-06 2014-01-09 Hoffmann-La Roche Inc. Antiviral compounds
EP3550031A1 (en) 2012-07-24 2019-10-09 Pharmacyclics, LLC Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (btk)
WO2014028931A2 (en) 2012-08-17 2014-02-20 Brandeis University Compounds and methods for treating mammalian gastrointestinal microbial infections
US20140205566A1 (en) 2012-11-30 2014-07-24 Novartis Ag Cyclic nucleuoside derivatives and uses thereof
BR112015017414A2 (pt) 2013-01-23 2017-07-11 Hoffmann La Roche derivados de triazol antivirais
RU2015136256A (ru) 2013-03-05 2017-04-10 Ф. Хоффманн-Ля Рош Аг Противовирусные соединения
MX2015015782A (es) 2013-05-16 2016-06-02 Riboscience Llc Derivados de nucleosido 4'-fluoro-2'-metil sustituido.
US20180200280A1 (en) 2013-05-16 2018-07-19 Riboscience Llc 4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication
MX2015015781A (es) 2013-05-16 2016-06-02 Riboscience Llc Derivados de nucleósido 4'-azido, 3'-deoxi-3'-fluoro sustituido.
BR112016009200A8 (pt) 2013-10-25 2020-03-24 Pharmacyclics Llc uso de um inibidor de btk e um inibidor imune do ponto de verificação
JP2017509336A (ja) 2014-03-20 2017-04-06 ファーマサイクリックス エルエルシー ホスホリパーゼｃガンマ２及び耐性に関連した変異
US10682369B2 (en) 2017-09-21 2020-06-16 Riboscience Llc 4′-fluoro-2′-methyl substituted nucleoside derivatives as inhibitors of HCV RNA replication
BR112020015572A2 (pt) 2018-01-31 2021-02-02 Deciphera Pharmaceuticals, Llc terapia de combinação para o tratamento da mastocitose
WO2019152711A1 (en) 2018-01-31 2019-08-08 Diciphera Pharmaceuticals Llc. Combination therapy for the treatment of gastrointestinal stromal tumors
WO2019191032A1 (en) 2018-03-26 2019-10-03 Clear Creek Bio, Inc. Compositions and methods for inhibiting dihydroorotate dehydrogenase
CN109970675A (zh) * 2018-05-28 2019-07-05 中国医学科学院医药生物技术研究所 一组硫脲化合物及其制备方法和应用
MY201990A (en) 2018-06-19 2024-03-27 Novartis Ag N-substituted tetrahydrothienopyridine derivatives and uses thereof
US12098117B2 (en) * 2018-12-11 2024-09-24 Duke University Compositions and methods for the treatment of cancer
CN114615982A (zh) 2019-08-12 2022-06-10 德西费拉制药有限责任公司 用于治疗胃肠道间质瘤的瑞普替尼
TWI878335B (zh) 2019-08-12 2025-04-01 美商迪賽孚爾製藥有限公司 治療胃腸道基質瘤方法
CN110590535A (zh) * 2019-10-12 2019-12-20 重庆医药高等专科学校 用二氧化硒氧化芳香乙酮制备芳香乙醛酸的方法
IL293866A (en) 2019-12-30 2022-08-01 Deciphera Pharmaceuticals Llc Amorphous kinase inhibitor formulations and methods of use thereof
FI4084779T3 (fi) 2019-12-30 2024-12-16 Deciphera Pharmaceuticals Llc 1-(4-bromi-5-(1-etyyli-7-(metyyliamino)-2-okso-1,2-dihydro-1,6-naftyridin-3-yyli)-2-fluorifenyyli)-3-fenyyliurean koostumuksia
US20210308117A1 (en) 2020-03-20 2021-10-07 Clear Creek Bio, Inc. Methods of treating viral infections using inhibitors of nucleotide synthesis pathways
WO2021209563A1 (en) 2020-04-16 2021-10-21 Som Innovation Biotech, S.A. Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus
US11779572B1 (en) 2022-09-02 2023-10-10 Deciphera Pharmaceuticals, Llc Methods of treating gastrointestinal stromal tumors

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1171904A (en) 1965-10-21 1969-11-26 Unilever Ltd Anilinobenzimidazoles having Antibacterial Properties
IL39336A0 (en) 1971-05-04 1972-07-26 Lilly Co Eli Substituted 2-anilinobenzoxazoles
DE2928485A1 (de) * 1979-07-14 1981-01-29 Bayer Ag Verwendung von harnstoffderivaten als arzneimittel bei der behandlung von fettstoffwechselstoerungen
US5283257A (en) 1992-07-10 1994-02-01 The Board Of Trustees Of The Leland Stanford Junior University Method of treating hyperproliferative vascular disease
WO1994012184A1 (en) 1992-11-24 1994-06-09 Syntex (U.S.A.) Inc. Use of mycophenolic acid, mycophenolate mofetil or derivate thereof to inhibit stenosis
US5444072A (en) 1994-02-18 1995-08-22 Syntex (U.S.A.) Inc. 6-substituted mycophenolic acid and derivatives
US5380879A (en) * 1994-02-18 1995-01-10 Syntex (U.S.A.) Inc. Derivatives of mycophenolic acid

Also Published As

Publication number Publication date
EA199800943A1 (ru) 1999-04-29
BR9708735A (pt) 1999-08-03
US6967214B2 (en) 2005-11-22
CN1116288C (zh) 2003-07-30
NZ332405A (en) 2000-06-23
PL192628B1 (pl) 2006-11-30
AP9700973A0 (en) 1997-07-31
IL126674A0 (en) 1999-08-17
AP813A (en) 2000-02-28
CZ298463B6 (cs) 2007-10-10
NO984917D0 (no) 1998-10-22
AU2678597A (en) 1997-11-12
BG102945A (en) 1999-08-31
IL126674A (en) 2005-08-31
BG64507B1 (bg) 2005-05-31
ID16664A (id) 1997-10-30
CN1219929A (zh) 1999-06-16
SK146198A3 (en) 1999-07-12
IN190508B (instruction) 2003-08-02
CA2252465A1 (en) 1997-10-30
WO1997040028A1 (en) 1997-10-30
CN1515248A (zh) 2004-07-28
US7329681B2 (en) 2008-02-12
NO984917L (no) 1998-12-23
TR199802136T2 (xx) 2001-06-21
CZ338098A3 (cs) 1999-02-17
PL329639A1 (en) 1999-04-12
US20050282876A1 (en) 2005-12-22
EP0902782A1 (en) 1999-03-24
US20030195202A1 (en) 2003-10-16
AU723730B2 (en) 2000-09-07
OA10902A (en) 2001-10-11
HUP0004421A2 (hu) 2001-04-28
NO312963B1 (no) 2002-07-22
HUP0004421A3 (en) 2002-10-28
EA004771B1 (ru) 2004-08-26
US6541496B1 (en) 2003-04-01
SK286662B6 (sk) 2009-03-05

Similar Documents

Publication Publication Date Title
CA2252465C (en) Urea derivatives as inhibitors of impdh enzyme
US6344465B1 (en) Inhibitors of IMPDH enzyme
US6054472A (en) Inhibitors of IMPDH enzyme
US6518291B1 (en) Inhibitors of IMPDH enzyme
US8268873B2 (en) Inhibitors of IMPDH enzyme
US5932600A (en) Inhibitors of IMPDH enzyme
KR20000010580A (ko) 아이엠피이디에치효소의억제제로서의우레아유도체
MXPA98008804A (en) Im enzyme inhibitors
EP1366766A1 (en) Inhibitors of IMPDH enzyme

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20140422