CA2264037A1 - Inhibiteurs de thrombine - Google Patents

Inhibiteurs de thrombine Download PDF

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Publication number
CA2264037A1
CA2264037A1 CA002264037A CA2264037A CA2264037A1 CA 2264037 A1 CA2264037 A1 CA 2264037A1 CA 002264037 A CA002264037 A CA 002264037A CA 2264037 A CA2264037 A CA 2264037A CA 2264037 A1 CA2264037 A1 CA 2264037A1
Authority
CA
Canada
Prior art keywords
mmol
alkyl
pct
solution
nmr
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.)
Abandoned
Application number
CA002264037A
Other languages
English (en)
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
Individual
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 Individual filed Critical Individual
Publication of CA2264037A1 publication Critical patent/CA2264037A1/fr
Abandoned 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

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)

Abstract

On décrit un composé qui inhibe la thrombine chez l'homme et qui est représenté par la formule générale (I) telle que la formule (a).
CA002264037A 1996-09-13 1997-09-09 Inhibiteurs de thrombine Abandoned CA2264037A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US2603396P 1996-09-13 1996-09-13
US60/026,033 1996-09-13
GBGB9624278.9A GB9624278D0 (en) 1996-11-22 1996-11-22 Thrombin inhibitors
GB9624278.9 1996-11-22
PCT/US1997/015989 WO1998010763A1 (fr) 1996-09-13 1997-09-09 Inhibiteurs de thrombine

Publications (1)

Publication Number Publication Date
CA2264037A1 true CA2264037A1 (fr) 1998-03-19

Family

ID=26310456

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002264037A Abandoned CA2264037A1 (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
US6716838B1 (en) 1999-05-19 2004-04-06 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
US6664255B1 (en) 1999-05-19 2003-12-16 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrazinones 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
US7015230B1 (en) 1999-05-19 2006-03-21 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils 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
US6867217B1 (en) 1999-05-19 2005-03-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade
US6750342B1 (en) 1999-05-19 2004-06-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrimidinones useful for selective inhibition of the coagulation cascade
AU2001243598A1 (en) 2000-03-13 2001-09-24 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted benzenes 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
DE60108948T2 (de) 2000-04-05 2005-11-03 Pharmacia Corp. Polyzyclisch aryl und heteroaryl substituierte 4-pyronen verwendbar als selektive hemmung von dem koagulationsprozess
US20040171616A9 (en) 2000-04-17 2004-09-02 South Michael S. Polycyclic aryl and heteroaryl substituted 1,4-quinones 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
JP2004517074A (ja) 2000-11-20 2004-06-10 ファルマシア・コーポレーション 凝血カスケードを選択的に阻害するのに有用な置換された多環アリールおよびヘテロアリールピリジン類
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
US7507767B2 (en) 2001-02-08 2009-03-24 Schering Corporation Cannabinoid receptor ligands
US7067539B2 (en) 2001-02-08 2006-06-27 Schering Corporation Cannabinoid receptor ligands
KR101009472B1 (ko) * 2001-06-12 2011-01-19 웰스테트 테라퓨틱스 코포레이션 대사 질환의 치료용 화합물
EP1438292A1 (fr) 2001-10-03 2004-07-21 Pharmacia Corporation Composes heterocycliques a 6 chainons utiles dans l'inhibition selective de la cascade de la coagulation
CA2462645A1 (fr) 2001-10-03 2003-11-13 Pharmacia Corporation Composes polycycliques a 5 elements substitues pour l'inhibition selective de la cascade de reactions dans la coagulation sanguine
US7071213B2 (en) 2001-11-14 2006-07-04 Schering Corporation Cannabinoid receptor ligands
ES2303599T3 (es) 2002-06-19 2008-08-16 Schering Corporation Agonistas de los receptores de cannabinoides.
US7120327B2 (en) 2002-11-27 2006-10-10 International Business Machines Corporation Backplane assembly with board to board optical interconnections
EP1601251B1 (fr) 2003-02-13 2014-11-12 Wellstat Therapeutics Corporation Composes pour le traitement de troubles metaboliques
AR043633A1 (es) 2003-03-20 2005-08-03 Schering Corp Ligandos de receptores de canabinoides
AU2007210014B2 (en) * 2006-02-01 2012-11-01 Merck Sharp & Dohme Corp. Potassium channel inhibitors
EP1981508A4 (fr) * 2006-02-01 2011-10-19 Merck Sharp & Dohme Inhibiteurs du canal potassique
AU2007209981B2 (en) * 2006-02-01 2011-11-24 Merck Sharp & Dohme Corp. Potassium channel inhibitors
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)

Family Cites Families (10)

* 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
IL87181A (en) * 1987-08-07 1993-08-18 Sanofi Sa Aminoalkoxyphenyl derivatives, their preparation and pharmaceutical and veterinary compositions containing them
US5084466A (en) * 1989-01-31 1992-01-28 Hoffmann-La Roche Inc. Novel carboxamide pyridine compounds which have useful pharmaceutical utility
JPH05503300A (ja) * 1990-11-15 1993-06-03 ペンタファルム　アクチェンゲゼルシャフト メタ置換フェニルアラニン誘導体
GB9214120D0 (en) * 1991-07-25 1992-08-12 Ici Plc Therapeutic amides
TW257757B (fr) * 1993-03-03 1995-09-21 Boehringer Mannheim Gmbh
US5530012A (en) * 1994-12-22 1996-06-25 Bristol-Myers Squibb Co. 3-alkoxybenzylpiperidine derivatives as melatonergic agents
IL117149A0 (en) * 1995-02-23 1996-06-18 Schering Corp Muscarinic antagonists
US5612363A (en) * 1995-06-02 1997-03-18 Berlex Laboratories, Inc. N,N-di(aryl) cyclic urea derivatives as anti-coagulants
ES2117950B1 (es) * 1996-08-02 1999-09-16 Univ Granada Nuevos compuestos que bloquean la biosintesis de fosforilcolina y su uso como segundo mensajero en proliferacion celular.

Also Published As

Publication number Publication date
AU4411797A (en) 1998-04-02
JP2001500864A (ja) 2001-01-23
AU725403B2 (en) 2000-10-12
EP0927035A4 (fr) 2002-11-13
EP0927035A1 (fr) 1999-07-07
WO1998010763A1 (fr) 1998-03-19

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