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EP0927035A4 - Inhibiteurs de thrombine - Google Patents

Inhibiteurs de thrombine

Info

Publication number
EP0927035A4
EP0927035A4 EP97942415A EP97942415A EP0927035A4 EP 0927035 A4 EP0927035 A4 EP 0927035A4 EP 97942415 A EP97942415 A EP 97942415A EP 97942415 A EP97942415 A EP 97942415A EP 0927035 A4 EP0927035 A4 EP 0927035A4
Authority
EP
European Patent Office
Prior art keywords
thrombin inhibitors
thrombin
inhibitors
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.)
Withdrawn
Application number
EP97942415A
Other languages
German (de)
English (en)
Other versions
EP0927035A1 (fr
Inventor
Adel M Naylor-Olsen
Gerald S Ponticello
Joseph P Vacca
Randall W Hungate
Craig Coburn
Brian T Phillips
S D Lewis
Mark E Fraley
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.)
Merck and Co Inc
Original Assignee
Merck and Co 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 GBGB9624278.9A external-priority patent/GB9624278D0/en
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Publication of EP0927035A1 publication Critical patent/EP0927035A1/fr
Publication of EP0927035A4 publication Critical patent/EP0927035A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
    • C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
    • C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • 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
    • C07D295/22—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 hetero atoms directly attached to ring nitrogen atoms
    • C07D295/26—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP97942415A 1996-09-13 1997-09-09 Inhibiteurs de thrombine Withdrawn EP0927035A4 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US2603396P 1996-09-13 1996-09-13
US26033P 1996-09-13
GB9624278 1996-11-22
GBGB9624278.9A GB9624278D0 (en) 1996-11-22 1996-11-22 Thrombin inhibitors
PCT/US1997/015989 WO1998010763A1 (fr) 1996-09-13 1997-09-09 Inhibiteurs de thrombine

Publications (2)

Publication Number Publication Date
EP0927035A1 EP0927035A1 (fr) 1999-07-07
EP0927035A4 true EP0927035A4 (fr) 2002-11-13

Family

ID=26310456

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97942415A Withdrawn EP0927035A4 (fr) 1996-09-13 1997-09-09 Inhibiteurs de thrombine

Country Status (5)

Country Link
EP (1) EP0927035A4 (fr)
JP (1) JP2001500864A (fr)
AU (1) AU725403B2 (fr)
CA (1) CA2264037A1 (fr)
WO (1) WO1998010763A1 (fr)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6133297A (en) * 1997-09-30 2000-10-17 Merck & Co., Inc. Thrombin inhibitors
US6664255B1 (en) 1999-05-19 2003-12-16 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade
US6458952B1 (en) 1999-05-19 2002-10-01 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade
US6716838B1 (en) 1999-05-19 2004-04-06 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
US6750342B1 (en) 1999-05-19 2004-06-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
US7015230B1 (en) 1999-05-19 2006-03-21 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade
US6867217B1 (en) 1999-05-19 2005-03-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade
US6653316B1 (en) 1999-05-19 2003-11-25 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
WO2001068605A1 (fr) 2000-03-13 2001-09-20 Pharmacia Corporation Benzenes polycycliques substitues aryle et heteroaryle utiles pour l'inhibition selective de la cascade de coagulation
US6875791B2 (en) 2000-04-05 2005-04-05 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 4-pyrones useful for selective inhibition of the coagulation cascade
EP1268428A2 (fr) 2000-04-05 2003-01-02 Pharmacia Corporation Pyridones polycycliques 4-aryl et heteroaryl substituees utiles pour l'inhibition selective de la cascade de coagulation
EP1274676A2 (fr) 2000-04-17 2003-01-15 Pharmacia Corporation 1,4-quinones polycycliques substituees par aryle et heteroaryles utiles pour l'inhibition selective des reactions en cascade provoquant la coagulation
US7015223B1 (en) 2000-11-20 2006-03-21 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl 1,2,4-triazinones useful for selective inhibition of the coagulation cascade
US7119094B1 (en) 2000-11-20 2006-10-10 Warner-Lambert Company Substituted polycyclic aryl and heteroarpyl pyrazinones useful for selective inhibition of the coagulation cascade
WO2002042272A2 (fr) 2000-11-20 2002-05-30 Pharmacia Corporation Aryl-et-heteroaryl-pyridines polycycliques substituees utiles dans l'inhibition selective de la cascade de la coagulation
US7067539B2 (en) 2001-02-08 2006-06-27 Schering Corporation Cannabinoid receptor ligands
US7507767B2 (en) 2001-02-08 2009-03-24 Schering Corporation Cannabinoid receptor ligands
IL159320A0 (en) * 2001-06-12 2004-06-01 Wellstat Therapeutics Corp Compounds for the treatment of metabolic disorders
CA2462305A1 (fr) 2001-10-03 2003-04-10 Michael S. South Composes heterocycliques a 6 chainons utiles dans l'inhibition selective de la cascade de la coagulation
MXPA04003170A (es) 2001-10-03 2004-07-08 Pharmacia Corp Compuestos policiclicos, sustituidos, provisto de 5 miembros, utiles para la inhibicion selectiva de la cascada de coagulacion.
WO2003042174A1 (fr) 2001-11-14 2003-05-22 Schering Corporation Ligands du recepteur des cannabinoides
CA2487346A1 (fr) 2002-06-19 2003-12-31 Schering Corporation Agonistes du recepteur cannabinoide
US7120327B2 (en) 2002-11-27 2006-10-10 International Business Machines Corporation Backplane assembly with board to board optical interconnections
KR101106631B1 (ko) * 2003-02-13 2012-01-20 웰스태트 테러퓨틱스 코포레이션 대사 질환의 치료용 화합물
AR043633A1 (es) 2003-03-20 2005-08-03 Schering Corp Ligandos de receptores de canabinoides
CA2641304A1 (fr) * 2006-02-01 2007-08-09 Merck & Co., Inc. Inhibiteurs du canal potassique
WO2007089679A2 (fr) * 2006-02-01 2007-08-09 Merck & Co., Inc. Inhibiteurs du canal potassique
EP1993551A4 (fr) * 2006-02-01 2011-10-19 Merck Sharp & Dohme Inhibiteurs du canal potassique
RU2354647C2 (ru) * 2007-06-28 2009-05-10 Общество С Ограниченной Ответственностью "Бионика" Новые соединения, обладающие функцией ингибиторов тромбина, и фармацевтические композиции на их основе
RU2353619C2 (ru) * 2007-06-28 2009-04-27 Общество С Ограниченной Ответственностью "Бионика" Новые соединения, обладающие функцией антикоагулянтов, фармацевтические композиции на их основе для лечения тромботических состояний и плазмозамещающий раствор для коррекции гиперкоагуляционных нарушений при гемодилюции
RU2469029C2 (ru) * 2010-12-30 2012-12-10 Закрытое Акционерное Общество "Вертекс" Вещество, обладающее сочетанной антиагрегантной, антикоагулянтной и вазодилаторной активностью, n,n'-замещенные пиперазины и способ их получения (варианты)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5283532A (en) * 1976-01-01 1977-07-12 Teijin Ltd Novel aromatic compounds
EP0302792A2 (fr) * 1987-08-07 1989-02-08 Sanofi Dérivés alkylaminoalkoxyphényls, procédé de préparation et compositions les contenant
EP0524781A1 (fr) * 1991-07-25 1993-01-27 Zeneca Limited Amides thérapeutiques
WO1994020467A1 (fr) * 1993-03-03 1994-09-15 Boehringer Mannheim Gmbh Nouvelles 4-aminopyridines, leur procede de preparation et medicaments contenant ces composes
EP0718286A1 (fr) * 1994-12-22 1996-06-26 Bristol-Myers Squibb Company Dérivé de 3-alkoxybenzylpiperidine utiles comme agents mélatonergique
WO1996026196A2 (fr) * 1995-02-23 1996-08-29 Schering Corporation Benzylpiperidines et piperazines utilisees comme antagonistes muscariniques
WO1998005644A1 (fr) * 1996-08-02 1998-02-12 Universidad De Granada Nouveaux composes avec activites selectives antitumorales, antivirales, antiparasitiques et antifongiques qui bloquent la biosynthese de la phosphorylcholline par inhibition selective de la choline kinase intracellulaire ou son utilisation en tant que second messager dans la proliferation cellulaire

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5084466A (en) * 1989-01-31 1992-01-28 Hoffmann-La Roche Inc. Novel carboxamide pyridine compounds which have useful pharmaceutical utility
KR920703558A (ko) * 1990-11-15 1992-12-18 원본미기재 메타-치환 페닐알라닌 유도체
US5612363A (en) * 1995-06-02 1997-03-18 Berlex Laboratories, Inc. N,N-di(aryl) cyclic urea derivatives as anti-coagulants

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5283532A (en) * 1976-01-01 1977-07-12 Teijin Ltd Novel aromatic compounds
EP0302792A2 (fr) * 1987-08-07 1989-02-08 Sanofi Dérivés alkylaminoalkoxyphényls, procédé de préparation et compositions les contenant
EP0524781A1 (fr) * 1991-07-25 1993-01-27 Zeneca Limited Amides thérapeutiques
WO1994020467A1 (fr) * 1993-03-03 1994-09-15 Boehringer Mannheim Gmbh Nouvelles 4-aminopyridines, leur procede de preparation et medicaments contenant ces composes
EP0718286A1 (fr) * 1994-12-22 1996-06-26 Bristol-Myers Squibb Company Dérivé de 3-alkoxybenzylpiperidine utiles comme agents mélatonergique
WO1996026196A2 (fr) * 1995-02-23 1996-08-29 Schering Corporation Benzylpiperidines et piperazines utilisees comme antagonistes muscariniques
WO1998005644A1 (fr) * 1996-08-02 1998-02-12 Universidad De Granada Nouveaux composes avec activites selectives antitumorales, antivirales, antiparasitiques et antifongiques qui bloquent la biosynthese de la phosphorylcholline par inhibition selective de la choline kinase intracellulaire ou son utilisation en tant que second messager dans la proliferation cellulaire

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
DATABASE CROSSFIRE BEILSTEIN Beilstein Institut zur Förderung der Chemischen Wissenschaften, Frankfurt am Main, DE; 27 June 1988 (1988-06-27), XP002213631 *
DATABASE WPI Section Ch Week 197734, Derwent World Patents Index; Class C02, AN 1977-60361Y, XP002213632 *
EFANGE ET AL: "Flexible N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Analogues: Synthesis Monamine Oxidase Catalyzed Bioactivation", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 33, no. 12, 1990, pages 3133 - 3142, XP002119483, ISSN: 0022-2623 *
J. PRAKT. CHEM., vol. 325, no. 2, 1983, pages 301 - 308 *
JAIN ET AL: "Chemical and pharmacological investigations of some.omega.-substituted alkylamino-3-aminopyridines", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 11, no. 1, 1968, pages 87 - 92, XP002093777, ISSN: 0022-2623 *
MAO S-S: "FACTOR XA INHIBITORS", PERSPECTIVES IN DRUG DISCOVERY AND DESIGN, ESCOM SCIENCE PUBLISHERS BV, XX, vol. 1, no. 3, 1993, pages 423 - 430, XP000654087, ISSN: 0928-2866 *
PROTIVA M ET AL: "1-ARYL- AND 1-(ARYLMETHYL)-4-GUANYLPIPERAZINES AND OTHER HETEROCYCLIC AND ALICYCLIC GUANIDINE DERIVATIVES", COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, ACADEMIC PRESS, LONDON, GB, vol. 40, 1975, pages 3904 - 3923, XP000574972, ISSN: 0010-0765 *
See also references of WO9810763A1 *
WALKER G N ET AL: "APPLICATION OF SODIUM BOROHYDRIDE, REDUCTION TO SYNTHESIS OF SUBSTITUTED AMINOPIPERIDINES, AMINOPIPERAZINES, AMINOPYRIDINES AND HYDRAZINES", JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY. EASTON, US, vol. 26, no. 8, 14 August 1961 (1961-08-14), pages 2740 - 2747, XP002071843, ISSN: 0022-3263 *

Also Published As

Publication number Publication date
CA2264037A1 (fr) 1998-03-19
AU725403B2 (en) 2000-10-12
AU4411797A (en) 1998-04-02
WO1998010763A1 (fr) 1998-03-19
EP0927035A1 (fr) 1999-07-07
JP2001500864A (ja) 2001-01-23

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