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

Urea derivatives as inhibitors of impdh enzyme Download PDF

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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
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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
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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
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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

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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)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Rheumatology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biotechnology (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 US5807876A (en) 1996-04-23 1996-04-23 Inhibitors of IMPDH enzyme
US08/636,361 1996-04-23
US08/801,780 1997-02-14
US08/801,780 US6344465B1 (en) 1996-04-23 1997-02-14 Inhibitors of IMPDH enzyme
US08/832,165 1997-04-02
US08/832,165 US6054472A (en) 1996-04-23 1997-04-02 Inhibitors of IMPDH enzyme
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) CN1515248A (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
UA66767C2 (uk) * 1996-10-18 2004-06-15 Вертекс Фармасьютикалс Інкорпорейтед Інгібітори серин-протеаз, фармацевтична композиція, спосіб інгібування активності та спосіб лікування або профілактики вірусної інфекції гепатиту с
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
DK1027328T3 (da) * 1997-10-31 2006-11-13 Aventis Pharma Ltd Substituerede anilider
WO1999032110A1 (en) * 1997-12-22 1999-07-01 Bayer Corporation INHIBITION OF p38 KINASE ACTIVITY USING ARYL AND HETEROARYL 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
ATE300299T1 (de) * 1997-12-22 2005-08-15 Bayer Pharmaceuticals Corp Inhibierung der raf-kinase durch substituierte heterocyclische harnstoffverbindungen
US7517880B2 (en) 1997-12-22 2009-04-14 Bayer Pharmaceuticals Corporation Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
JP2002512997A (ja) * 1998-04-29 2002-05-08 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 Ｉｍｐｄｈ酵素のインヒビター
US6313071B1 (en) * 1998-06-04 2001-11-06 Kumiai Chemical Industry Co., Ltd. Phenylacetylene derivatives and agricultural/horticultural fungicides
CA2342626A1 (en) * 1998-10-22 2000-05-04 Neurosearch A/S Substituted phenyl derivatives, their preparation and use
CA2348234A1 (en) 1998-10-29 2000-05-11 Chunjian Liu Compounds derived from an amine nucleus that are inhibitors of impdh enzyme
EP1127054A4 (en) 1998-10-29 2006-11-02 Bristol Myers Squibb Co 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
US6420403B1 (en) 1998-10-29 2002-07-16 Edwin J. Iwanowicz Inhibitors of IMPDH enzyme
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
DE69917673T2 (de) * 1998-12-09 2005-06-09 Wyeth Alpha-methylbenzyl-enthaltende thioharnstoffe als inhibitoren von herpes-viren mit einer phenylenediamingruppe
AU1934500A (en) * 1998-12-09 2000-06-26 Wyeth Thiourea inhibitors of herpes viruses
US6262090B1 (en) 1998-12-09 2001-07-17 American Home Products Corporation Aminopyridine-containing thiourea inhibitors of herpes viruses
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
US6337338B1 (en) 1998-12-15 2002-01-08 Telik, Inc. Heteroaryl-aryl ureas as IGF-1 receptor antagonists
EP1142868A4 (en) * 1998-12-22 2004-09-29 Mitsubishi Chem Corp AMIDE DERIVATIVES
ATE556713T1 (de) 1999-01-13 2012-05-15 Bayer Healthcare Llc Omega-carboxyarylsubstituierte-diphenyl- harnstoffe als p38-kinasehemmer
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7928239B2 (en) 1999-01-13 2011-04-19 Bayer Healthcare Llc Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
EP1140840B1 (en) 1999-01-13 2006-03-22 Bayer Pharmaceuticals Corp. -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
RU2319693C9 (ru) 1999-01-13 2008-08-20 Байер Копэрейшн Производные мочевины (варианты), фармацевтическая композиция (варианты) и способ лечения заболевания, связанного с ростом раковых клеток (варианты)
NZ528846A (en) * 1999-03-12 2005-05-27 Boehringer Ingelheim Pharma Compounds useful as anti-inflammatory agents
AR029341A1 (es) 1999-03-19 2003-06-25 Vertex Pharma Inhibidores de la enzima impdh (inosina-5'-monofosfato dehidrogenasa)
US6653309B1 (en) 1999-04-26 2003-11-25 Vertex Pharmaceuticals Incorporated Inhibitors of IMPDH enzyme technical field of the invention
AU5031200A (en) * 1999-05-28 2000-12-18 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.
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
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
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
CA2407370A1 (en) * 2000-04-24 2001-11-01 Bristol-Myers Squibb Company 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
AU2003209116A1 (en) 2002-02-11 2003-09-04 Bayer Pharmaceuticals Corporation Aryl ureas with angiogenesis inhibiting activity
SI1580188T1 (sl) 2002-02-11 2012-02-29 Bayer Healthcare Llc Aril sečnine kot kinazni inhibitorji
EP1402887A1 (en) * 2002-09-18 2004-03-31 Jerini AG New compounds for the inhibition of undesired cell proliferation and use thereof
EP1575579B1 (en) * 2002-12-06 2009-03-04 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
BRPI0412219B8 (pt) 2003-07-23 2021-07-27 Bayer Healthcare Llc compostos ômega-carboxi aril difenil uréia fluoro substituídos e composições farmacêuticas compreendendo os referidos compostos
TWI359147B (en) 2003-09-05 2012-03-01 Vertex Pharma Inhibitors of serine proteases, particularly hcv n
EP2361925A1 (en) 2003-10-10 2011-08-31 Vertex Pharmaceuticals Incorporated Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
AR045870A1 (es) * 2003-10-11 2005-11-16 Vertex Pharma Terapia de combinacion para la infeccion de virus de hepatitis c
AU2004285019B9 (en) * 2003-10-27 2011-11-24 Vertex Pharmaceuticals Incorporated HCV NS3-NS4A protease resistance mutants
EP1944042A1 (en) 2003-10-27 2008-07-16 Vertex Pharmceuticals Incorporated Combinations for HCV treatment
JP2008505849A (ja) 2004-02-04 2008-02-28 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 セリンプロテアーゼ、特に、ｈｃｖ、ｎｓ３−ｎｓ４ａプロテアーゼの阻害剤
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
CA2571710A1 (en) 2004-06-24 2006-11-02 Nicholas Valiante Small molecule immunopotentiators and assays for their detection
ATE412652T1 (de) 2004-08-12 2008-11-15 Pfizer Triazolopyridinylsulfanylderivate als inhibitoren der p38-map-kinase
JP2008514723A (ja) * 2004-10-01 2008-05-08 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プロテアーゼの阻害
TW201424733A (zh) 2004-10-29 2014-07-01 Vertex Pharma 劑量型式
EP1858877B1 (en) * 2005-01-14 2014-03-12 Gilead Connecticut, Inc. 1,3 substituted diaryl ureas as modulators of kinase activity
EP1858879B1 (en) * 2005-01-14 2012-06-06 Gilead Connecticut, Inc. 1,3-diaryl substituted ureas as modulators of kinase activity
WO2006086500A2 (en) * 2005-02-08 2006-08-17 Aspreva Pharmaceuticals Sa Compositions and methods for treating vascular, autoimmune and inflammatory diseases
WO2006086498A2 (en) * 2005-02-08 2006-08-17 Aspreva Pharmaceuticals Sa Treatment of vascular, autoimmune and inflammatory diseases using low dosages of impdh inhibitors
UA93673C2 (ru) 2005-03-07 2011-03-10 Баер Шеринг Фарма Акциенгезельшафт Фармацевтическая композиция, которая содержит омега-карбоксиарилзамещенную дифенилмочевину, для лечения paka
WO2007024294A2 (en) * 2005-05-03 2007-03-01 Cgi Pharmaceuticals, Inc. Certain substituted ureas, as modulators of kinase activity
CA2606780A1 (en) * 2005-05-09 2006-11-16 Vertex Pharmaceuticals Incorporated Processes for preparing biaryl ureas and analogs thereof
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
CN101273042B (zh) 2005-07-29 2013-11-06 泰博特克药品有限公司 丙型肝炎病毒的大环抑制剂
PE20070210A1 (es) 2005-07-29 2007-04-16 Tibotec Pharm Ltd Compuestos macrociclicos como inhibidores del virus de hepatitis c
JO2768B1 (en) 2005-07-29 2014-03-15 تيبوتيك فارماسيوتيكالز ليمتد Large cyclic inhibitors of hepatitis C virus
PL1913015T3 (pl) 2005-07-29 2014-04-30 Janssen R&D Ireland Makrocykliczne inhibitory wirusa zapalenia wątroby typu C
PE20070211A1 (es) 2005-07-29 2007-05-12 Medivir Ab Compuestos macrociclicos como inhibidores del virus de hepatitis c
SI1919898T1 (sl) 2005-07-29 2011-05-31 Tibotec Pharm Ltd Makrociklični inhibitorji virusa hepatitisa C
TWI382025B (zh) 2005-07-29 2013-01-11 Tibotec Pharm Ltd Ｃ型肝炎病毒之大環抑制劑（四）
MY139988A (en) 2005-07-29 2009-11-30 Tibotec Pharm Ltd Macrocylic inhibitors of hepatitis c virus
ES2373685T3 (es) 2005-07-29 2012-02-07 Tibotec Pharmaceuticals Inhibidores macrocíclicos del virus de la hepatitis c.
KR20080033481A (ko) 2005-08-02 2008-04-16 버텍스 파마슈티칼스 인코포레이티드 세린 프로테아제의 억제제
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
EP2392590A3 (en) 2005-11-11 2012-03-14 Vertex Pharmaceuticals Incorporated Hepatitis C virus variants
JP5436864B2 (ja) 2006-02-27 2014-03-05 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 Ｖｘ−９５０を含む共結晶体およびそれを含む医薬組成物
WO2007109080A2 (en) 2006-03-16 2007-09-27 Vertex Pharmaceuticals Incorporated Deuterated hepatitis c protease inhibitors
JP5167244B2 (ja) 2006-04-11 2013-03-21 ノバルティス アーゲー Ｈｃｖ／ｈｉｖ阻害剤およびそれらの使用
WO2008039794A1 (en) * 2006-09-25 2008-04-03 Arete Therapeutics, Inc. Soluble epoxide hydrolase inhibitors
WO2008040778A2 (en) 2006-10-04 2008-04-10 Tibotec Pharmaceuticals Ltd. Carboxamide 4-[(4-pyridyl)amino] pyrimidines for the treatment of hepatitis c
AR064258A1 (es) 2006-11-17 2009-03-25 Tibotec Pharm Ltd Inhibidores macrociclicos del virus de hepatitis c
NZ579295A (en) * 2007-02-27 2012-03-30 Vertex Pharma Inhibitors of serine proteases
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
KR20100014811A (ko) * 2007-04-20 2010-02-11 데시페라 파마슈티칼스, 엘엘씨. 골수증식성 질환 및 기타 증식성 질환의 치료에 유용한 키나제 억제제
CN102872461A (zh) 2007-05-04 2013-01-16 弗特克斯药品有限公司 用于治疗hcv感染的组合治疗
TW200922933A (en) * 2007-08-30 2009-06-01 Vertex Pharma Co-crystals and pharmaceutical compositions comprising the same
BRPI0821836A2 (pt) 2007-12-24 2015-06-16 Tibotec Pharm Ltd Indóis 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
PT2331554E (pt) 2008-08-14 2013-05-21 Janssen R & D Ireland Derivados de indol macrocíclicos úteis como inibidores do vírus da hepatite c
US9120779B2 (en) 2008-12-03 2015-09-01 Presidio Pharmaceuticals, Inc. Inhibitors of HCV NS5A
AU2009322393B2 (en) 2008-12-03 2017-02-02 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
CA2755658A1 (en) 2009-03-27 2010-09-30 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
US20110027229A1 (en) 2009-07-31 2011-02-03 Medtronic, Inc. Continuous subcutaneous administration of interferon-alpha to hepatitis c infected patients
UA108211C2 (uk) 2009-11-04 2015-04-10 Янссен Рід Айрленд Бензімідазолімідазольні похідні
WO2011094489A1 (en) 2010-01-29 2011-08-04 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
WO2011149856A1 (en) 2010-05-24 2011-12-01 Presidio Pharmaceuticals, Inc. Inhibitors of hcv ns5a
NZ604040A (en) 2010-06-03 2015-02-27 Pharmacyclics Inc The use of inhibitors of bruton’s tyrosine kinase (btk)
WO2011156545A1 (en) 2010-06-09 2011-12-15 Vertex Pharmaceuticals Incorporated Viral dynamic model for hcv combination therapy
AU2011268922B2 (en) 2010-06-24 2014-06-12 Janssen Sciences Ireland Uc Preparation of 13-cyclohexyl-3-methoxy-6-[methyl-(2-{2-[methyl-(sulphamoyl)-amino]-ethoxy}-ethyl)-carbamoyl]-7H-indolo-[2,1-a]-[2]-benzazepine-10-carboxylic acid
EP2593105A1 (en) 2010-07-14 2013-05-22 Vertex Pharmaceuticals Incorporated Palatable pharmaceutical composition comprising vx-950
AR082619A1 (es) 2010-08-13 2012-12-19 Hoffmann La Roche Inhibidores del virus de la hepatitis c
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
WO2012175700A1 (en) 2011-06-23 2012-12-27 Digna Biotech, S. L. Treatment of chronic hepatitis c with ifn-a5 combined with ifn-a2b in a cohort of patients
US20120328565A1 (en) 2011-06-24 2012-12-27 Brinkman John A Antiviral compounds
HK1199454A1 (en) 2011-10-10 2015-07-03 F. Hoffmann-La Roche Ag Antiviral compounds
WO2013087743A1 (en) 2011-12-16 2013-06-20 F. Hoffmann-La Roche Ag Inhibitors of hcv ns5a
PL2794629T3 (pl) 2011-12-20 2018-02-28 Riboscience Llc 2',4'-difluoro-2'-metylo-podstawione pochodne nukleozydowe jako inhibitory replikacji rna hcv
CN108409820A (zh) 2011-12-20 2018-08-17 里博科学有限责任公司 作为hcv rna复制抑制剂的4′-叠氮基，3′-氟取代的核苷衍生物
JP6170944B2 (ja) 2011-12-28 2017-07-26 ヤンセン・サイエンシズ・アイルランド・ユーシー Ｈｃｖ阻害剤としてのヘテロ−二環式誘導体
US20130195797A1 (en) 2012-01-31 2013-08-01 Vertex Pharmaceuticals Incorporated High potency formulations of vx-950
BR112014015582A8 (pt) 2012-02-24 2017-07-04 Hoffmann La Roche compostos antivirais
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
CN104704129A (zh) 2012-07-24 2015-06-10 药品循环公司 与对布鲁顿酪氨酸激酶(btk)抑制剂的抗性相关的突变
US9447134B2 (en) 2012-08-17 2016-09-20 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
KR20150109451A (ko) 2013-01-23 2015-10-01 에프. 호프만-라 로슈 아게 항바이러스성 트라이아졸 유도체
KR20150114566A (ko) 2013-03-05 2015-10-12 에프. 호프만-라 로슈 아게 항바이러스 화합물
MA38675A1 (fr) 2013-05-16 2017-12-29 Riboscience Llc Dérivés de nucléosides 4'-fluoro-2'-méthyle substitués utiles pour inhiber la replication de l'hepatite c (hcv)
US20180200280A1 (en) 2013-05-16 2018-07-19 Riboscience Llc 4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication
EP2996696A4 (en) 2013-05-16 2016-12-21 Riboscience Llc 4'-AZIDO, 3'-DEOXY-3'-FLUOR-SUBSTITUTED NUCLEOSIDE DERIVATIVES
WO2015061752A1 (en) 2013-10-25 2015-04-30 Pharmacyclics, Inc. Treatment using bruton's tyrosine kinase inhibitors and immunotherapy
WO2015143400A1 (en) 2014-03-20 2015-09-24 Pharmacyclics, Inc. Phospholipase c gamma 2 and resistance associated mutations
WO2019060740A1 (en) 2017-09-21 2019-03-28 Riboscience Llc 4'-FLUORO-2'-METHYL SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF HCV RNA REPLICATION
CA3089630A1 (en) 2018-01-31 2019-08-08 Deciphera Pharmaceuticals, Llc Combination therapy for the treatment of mastocytosis
CN118416236A (zh) 2018-01-31 2024-08-02 德西费拉制药有限责任公司 治疗胃肠道间质瘤的组合疗法
AU2019242628A1 (en) 2018-03-26 2020-09-24 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
IL279441B2 (en) 2018-06-19 2023-06-01 Novartis Ag History of n-converted tetrahydrothinopyridines and their uses
WO2020123675A1 (en) * 2018-12-11 2020-06-18 Duke University Compositions and methods for the treatment of cancer
CA3150433A1 (en) 2019-08-12 2021-02-18 Deciphera Pharmaceuticals, Llc Ripretinib for treating gastrointestinal stromal tumors
WO2021030405A1 (en) 2019-08-12 2021-02-18 Deciphera Pharmaceuticals, Llc Ripretinib for treating gastrointestinal stromal tumors
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
SMT202300467T1 (it) 2019-12-30 2024-01-10 Deciphera Pharmaceuticals Llc Formulazioni di inibitori di chinasi amorfi e loro procedimenti d’uso
LT4084779T (lt) 2019-12-30 2024-11-11 Deciphera Pharmaceuticals, Llc 1-(4-brom-5-(1-etil-7-(metilamino)-2-okso-1,2-dihidro-1,6-naftiridin-3-il) -2- fluorfenil)-3-fenilkarbamido kompozicijos
US20210290651A1 (en) 2020-03-20 2021-09-23 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
CA985286A (en) 1971-05-04 1976-03-09 Charles J. Paget (Jr.) (substituted anilino) benzoxazoles useful in the prophylaxis of mareks disease
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

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