CA2264037A1 - Inhibiteurs de thrombine - Google Patents

Inhibiteurs de thrombine Download PDF

Info

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

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (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
GB9624278.9 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 (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
US6750342B1 (en) 1999-05-19 2004-06-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrimidinones 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
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
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
US6867217B1 (en) 1999-05-19 2005-03-15 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridones 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
US6693121B2 (en) 2000-04-05 2004-02-17 Pharmacia Corporation Polycyclic aryl and heteroaryl substituted 4-pyridones useful for selective inhibition of the coagulation cascade
US20020022604A1 (en) 2000-04-05 2002-02-21 South Michael S. Polycyclic aryl and heteroaryl substituted 4-pyrones useful for selective inhibition of the coagulation cascade
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
CA2430037A1 (fr) 2000-11-20 2002-05-30 Michael S. South Aryl-et-heteroaryl-pyridines polycycliques substituees utiles dans l'inhibition selective de la cascade de la coagulation
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
WO2002100341A2 (fr) * 2001-06-12 2002-12-19 Wellstat Therapeutics Corporation Composes destines au traitement de troubles metaboliques
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
US7105559B2 (en) 2001-10-03 2006-09-12 Pharmacia Corporation Substituted 5-membered polycyclic compounds useful for selective inhibition of the coagulation cascade
PL369952A1 (en) 2001-11-14 2005-05-02 Schering Corporation Cannabinoid receptor ligands
WO2004000807A1 (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
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
JP5190381B2 (ja) * 2006-02-01 2013-04-24 メルク・シャープ・エンド・ドーム・コーポレイション カリウムチャネル阻害剤
AU2007209981B2 (en) * 2006-02-01 2011-11-24 Merck Sharp & Dohme Corp. Potassium channel inhibitors
CA2641304A1 (fr) * 2006-02-01 2007-08-09 Merck & Co., Inc. Inhibiteurs du canal potassique
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
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
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
US5518735A (en) * 1990-11-15 1996-05-21 Pentapharm Ag Meta-substituted phenylalanine derivatives
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
EP0927035A1 (fr) 1999-07-07
EP0927035A4 (fr) 2002-11-13
AU4411797A (en) 1998-04-02
JP2001500864A (ja) 2001-01-23
AU725403B2 (en) 2000-10-12
WO1998010763A1 (fr) 1998-03-19

Similar Documents

Publication Publication Date Title
CA2264037A1 (fr) Inhibiteurs de thrombine
EP0931788B1 (fr) Inhibiteurs de la métalloprotéinase
EP0363963B1 (fr) Benzimidazoles pipéridinyliques comme antihistaminiques
US5872138A (en) Thrombin inhibitors
US5332751A (en) Pyridine carboxamide compounds which have useful as pharmaceutical utility
NZ311410A (en) 2-(naphthyl or phenyl) substituted phenyl sulphonylamino derivatives useful as factor Xa inhibitors
WO1994018161A1 (fr) Sulfamides de phenyle substitues utilises comme agonistes a selectivite beta 3 dans le traitement du diabete et de l'obesite
WO2000077027A2 (fr) Composes
CZ183399A3 (cs) Benzamidoaldehydy a jejich použití
PL198032B1 (pl) Pochodne amidów, sposób ich wytwarzania, ich zastosowanie oraz zawierające je kompozycje farmaceutyczne
SK174899A3 (en) Urokinase inhibitors
JP2001508796A (ja) トロンビン阻害薬
PL180042B1 (en) Amides of sulphonanamidocarbonylopyridine 2-carboxylic acids and their pyridinic n-oxides, method of obtaining them and therapeutic agents containing such compounds
WO2003050088A1 (fr) Carboxamides heterocycliques substitues a action antithrombotique
WO2000005214A2 (fr) Isoquinoleines utilisees en tant qu'inhibiteurs de l'urokinase
WO2004026851A1 (fr) Derives de 4-hydroxyphenyl-3-3,5-disubstitue-propionamide en tant qu'inhibiteurs de cathepsine b
EP0558677B1 (fr) Amines biologiquement actives
CA2310331A1 (fr) Derives de biphenylamidine
AU736511B2 (en) Matrix metalloprotease inhibitors
US20050043304A1 (en) Novel amine derivative having human beta-tryptase inhibitory activity and drugs containing the same
US6284796B1 (en) Ukokinase inhibitors
AU739766B2 (en) Antivirals
OA11578A (en) Isoquinolines as urokinase inhibitors.
MXPA00006973A (en) Antivirals
KR20010081600A (ko) 선택적 ＦＸａ 억제활성을 갖는 알라닌 유도체

Legal Events

Date Code Title Description
EEER Examination request
FZDE Dead