DE69532754D1 - Faktor xa inhibitoren - Google Patents

Faktor xa inhibitoren

Info

Publication number
DE69532754D1
DE69532754D1 DE69532754T DE69532754T DE69532754D1 DE 69532754 D1 DE69532754 D1 DE 69532754D1 DE 69532754 T DE69532754 T DE 69532754T DE 69532754 T DE69532754 T DE 69532754T DE 69532754 D1 DE69532754 D1 DE 69532754D1
Authority
DE
Germany
Prior art keywords
activity
factor
compound
amino acids
provides
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 - Lifetime
Application number
DE69532754T
Other languages
English (en)
Other versions
DE69532754T2 (de
Inventor
Fahad Al-Obeidi
Michal Lebl
A Ostrem
Pavel Safar
Alena Stierandova
Peter Strop
Armin Walser
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.)
Aventis Pharmaceuticals Inc
Original Assignee
Aventis 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
Application filed by Aventis Pharmaceuticals Inc filed Critical Aventis Pharmaceuticals Inc
Publication of DE69532754D1 publication Critical patent/DE69532754D1/de
Application granted granted Critical
Publication of DE69532754T2 publication Critical patent/DE69532754T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • 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
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0207—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)4-C(=0), e.g. 'isosters', replacing two amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06086—Dipeptides with the first amino acid being basic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0815—Tripeptides with the first amino acid being basic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64—Cyclic peptides containing only normal peptide links
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/56—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
DE69532754T 1994-04-26 1995-04-25 Faktor xa inhibitoren Expired - Lifetime DE69532754T2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US23305494A 1994-04-26 1994-04-26
US233054 1994-04-26
PCT/US1995/005268 WO1995029189A1 (en) 1994-04-26 1995-04-25 FACTOR Xa INHIBITORS

Publications (2)

Publication Number Publication Date
DE69532754D1 true DE69532754D1 (de) 2004-04-29
DE69532754T2 DE69532754T2 (de) 2005-03-10

Family

ID=22875692

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69532754T Expired - Lifetime DE69532754T2 (de) 1994-04-26 1995-04-25 Faktor xa inhibitoren

Country Status (27)

Country Link
EP (2) EP0758341B1 (de)
JP (1) JP3655632B2 (de)
KR (1) KR100380124B1 (de)
CN (1) CN1181091C (de)
AT (1) ATE262536T1 (de)
AU (1) AU707653B2 (de)
CA (1) CA2186497C (de)
CZ (1) CZ296439B6 (de)
DE (1) DE69532754T2 (de)
DK (1) DK0758341T3 (de)
EE (1) EE03973B1 (de)
ES (1) ES2214500T3 (de)
FI (1) FI120494B (de)
HU (1) HUT76346A (de)
IL (1) IL113505A (de)
LT (1) LT4218B (de)
LV (1) LV11740B (de)
NO (1) NO318759B1 (de)
NZ (1) NZ284977A (de)
PL (1) PL188132B1 (de)
PT (1) PT758341E (de)
RU (1) RU2152954C1 (de)
SI (1) SI9520044B (de)
SK (1) SK286094B6 (de)
TW (1) TW409129B (de)
WO (1) WO1995029189A1 (de)
ZA (1) ZA953361B (de)

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EP0873356A1 (de) * 1995-02-17 1998-10-28 Basf Aktiengesellschaft Neue dipeptidische amidine als thrombin-inhibitoren
US6069130A (en) * 1995-06-07 2000-05-30 Cor Therapeutics, Inc. Ketoheterocyclic inhibitors of factor Xa
US5747458A (en) * 1995-06-07 1998-05-05 Chiron Corporation Urokinase receptor ligands
US5766932A (en) * 1995-12-20 1998-06-16 Hoechst Marion Roussel, Inc. Process for preparing N-acetyl(L)-4-cyanophenylalanine from a mixture of the corresponding D,L ethyl esters using subtilisin
DE69623038T2 (de) * 1995-12-20 2002-12-12 Aventis Pharma Inc Verfahren zur herstellung von n-acetyl(l)-4-cyanophenylalanin ac-(l)-phe(4-cn)-phe(4-cn)-oh und n-acetyl-(l)-p-amidinophenylalanin-cyclohexylglycin-beta-(3-n-methylpyridinium)-alanin ac-(l)-paph-chg-palme(3)-nh2
US6063794A (en) 1996-10-11 2000-05-16 Cor Therapeutics Inc. Selective factor Xa inhibitors
US6369080B2 (en) 1996-10-11 2002-04-09 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6194435B1 (en) 1996-10-11 2001-02-27 Cor Therapeutics, Inc. Lactams as selective factor Xa inhibitors
US6262047B1 (en) 1996-10-11 2001-07-17 Cor Therapeutics, Inc. Selective factor Xa inhibitors
NZ500353A (en) 1997-04-14 2002-02-01 Cor Therapeutics Inc Cyclic diaza compounds that are selective inhibitors of factor Xa
NZ500352A (en) 1997-04-14 2001-10-26 Cor Therapeutics Inc Cyclic diaza selective factor Xa inhibitors
JP2001521524A (ja) * 1997-04-14 2001-11-06 シーオーアール セラピューティクス インコーポレイテッド 選択的Ｘａ因子阻害剤
US7109326B2 (en) 1997-04-15 2006-09-19 Genentech, Inc. Halo-alkoxycarbonyl prodrugs
US6333321B1 (en) 1997-08-11 2001-12-25 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6218382B1 (en) 1997-08-11 2001-04-17 Cor Therapeutics, Inc Selective factor Xa inhibitors
US6228854B1 (en) 1997-08-11 2001-05-08 Cor Therapeutics, Inc. Selective factor Xa inhibitors
GB9727123D0 (en) * 1997-12-22 1998-02-25 Int Centre Genetic Eng & Bio Synthesis of diamines
CA2316172C (en) 1997-12-24 2010-02-02 Aventis Pharma Deutschland Gmbh Indole derivatives as inhibitors of factor xa
EP0987274A1 (de) * 1998-09-15 2000-03-22 Hoechst Marion Roussel Deutschland GmbH Faktor VIIa Inhibitore
EP1016663A1 (de) * 1999-01-02 2000-07-05 Aventis Pharma Deutschland GmbH Neue Malonsäure Derivate, Verfahren zu ihrer Herstellung, ihre Verwendung und pharmazeutische Zusammensetzungen sie enthaltend (Inhibierung der Faktor Xa Aktivität)
CA2358578A1 (en) * 1999-01-02 2000-07-13 Aventis Pharma Deutschland Gmbh Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor xa activity)
CA2358581C (en) 1999-01-02 2010-02-02 Aventis Pharma Deutschland Gmbh Arylalkanoyl derivatives, processes for their preparation, their use and pharmaceutical compositions containing them
EP1022268A1 (de) * 1999-01-02 2000-07-26 Aventis Pharma Deutschland GmbH Arylalkanoylderivate, Verfahren zu ihrer Herstellung, ihre Verwendung und diese enthaltende pharmazeutische Zubereitungen
EP1059302A1 (de) * 1999-06-08 2000-12-13 Aventis Pharma Deutschland GmbH Faktor VIIa Inhibitore
EP1095933A1 (de) 1999-10-30 2001-05-02 Aventis Pharma Deutschland GmbH N-Guanidinoalkylamide, Verfahren zu ihrer Herstellung, ihre Verwendung und pharmazeutische Zusammensetzungen, die sie enthalten
JP5088598B2 (ja) * 1999-12-14 2012-12-05 昭和電工株式会社 シアノベンジルアミン類の塩の製造方法
AU1890201A (en) * 1999-12-14 2001-06-25 Showa Denko Kabushiki Kaisha Process for producing salt of cyanobenzylamine or derivative
IL150897A0 (en) * 2000-01-28 2003-02-12 Aventis Pharma Gmbh Process for the preparation of acetyl-amidiniophenylalanyl cyclohexylglycyl-pyridinioalaninamides
EP1127884A1 (de) * 2000-02-26 2001-08-29 Aventis Pharma Deutschland GmbH Neue Malonsäure Derivaie, Verfahren zu ihrer Herstellung, ihre Verwendung als Inhibitor der Faktor XA Aktivtät und pharmazeutische Zusammensetzungen diese enthaltend
DE10029015A1 (de) * 2000-06-15 2001-12-20 Curacyte Ag Hemmstoffe für den Gerinnungsfaktor Xa
BR0115938A (pt) 2000-12-06 2003-12-23 Aventis Pharma Deustschland Gm Derivados de guanidina e amidina com inibidores do fator xa
EP1314733A1 (de) 2001-11-22 2003-05-28 Aventis Pharma Deutschland GmbH Indol-2-carbonsäureamide als Faktor-Xa-Hemmer
WO2003076391A2 (de) 2002-03-11 2003-09-18 Curacyte Ag Hemmstoffe der urokinase, ihre herstellung und verwendung
WO2004050637A2 (en) 2002-12-03 2004-06-17 Axys Pharmaceuticals, Inc. 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine derivatives as factor viia inhibitors
US7358268B2 (en) 2002-12-04 2008-04-15 Sanofi-Aventis Deutschland Gmbh Imidazole derivatives as factor Xa inhibitors
US7429581B2 (en) 2002-12-23 2008-09-30 Sanofi-Aventis Deutschland Gmbh Pyrazole-derivatives as factor Xa inhibitors
DE10301300B4 (de) 2003-01-15 2009-07-16 Curacyte Chemistry Gmbh Verwendung von acylierten 4-Amidino- und 4-Guanidinobenzylaminen zur Inhibierung von Plasmakallikrein
US7317027B2 (en) 2003-05-19 2008-01-08 Sanofi-Aventis Deutschland Gmbh Azaindole-derivatives as factor Xa inhibitors
EP1479677A1 (de) 2003-05-19 2004-11-24 Aventis Pharma Deutschland GmbH Neue Indolderivate als Faktor Xa-Inhibitoren
EP1479680A1 (de) 2003-05-19 2004-11-24 Aventis Pharma Deutschland GmbH Azaindole-Derivative als Faktor Xa Hemmer
US7223780B2 (en) 2003-05-19 2007-05-29 Sanofi-Aventis Deutschland Gmbh Triazole-derivatives as blood clotting enzyme factor Xa inhibitors
EP1479675A1 (de) 2003-05-19 2004-11-24 Aventis Pharma Deutschland GmbH Indazolderivate als Faktor Xa-Inhibitoren
US7741341B2 (en) 2003-05-19 2010-06-22 Sanofi-Aventis Deutschland Gmbh Benzimidazole-derivatives as factor Xa inhibitors
DE10342108A1 (de) 2003-09-11 2005-04-14 Curacyte Chemistry Gmbh Basisch-substituierte Benzylaminanaloga als Inhibitoren des Gerinnungsfaktors Xa, ihre Herstellung und Verwendung
EP1568698A1 (de) 2004-02-27 2005-08-31 Aventis Pharma Deutschland GmbH Pyrrolderivate als faktor-xa-inhibitoren
EP1807082A4 (de) 2004-10-26 2010-12-01 Janssen Pharmaceutica Nv Faktor-xa-verbindungen
EP1724269A1 (de) 2005-05-20 2006-11-22 Sanofi-Aventis Deutschland GmbH Heteroarylcarbonsäure-sulfamoylalkylamidderivate als Faktor Xa-Inhibitoren
DE102005044319A1 (de) 2005-09-16 2007-03-22 Curacyte Chemistry Gmbh 2-(Aminomethyl)-5-Chlor-Benzylamid-Derivate und ihre Verwendung als Hemmstoffe des Gerinnungsfaktors Xa
DE102006050672A1 (de) 2006-10-24 2008-04-30 Curacyte Discovery Gmbh Hemmstoffe des Plasmins und des Plasmakallikreins
EP1918718A1 (de) * 2006-10-31 2008-05-07 Roche Diagnostics GmbH Verfahren und Vorrichtungen zur elektrochemischen Bestimmung von Faktor Xa-Inhibitoren in Blutproben
CN101743001B (zh) 2007-04-13 2013-02-06 千年药品公司 用起因子xa抑制剂作用的化合物的组合抗凝治疗

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Also Published As

Publication number Publication date
AU2368395A (en) 1995-11-16
CN1147261A (zh) 1997-04-09
EE03973B1 (et) 2003-02-17
EP0758341A1 (de) 1997-02-19
SI9520044B (sl) 2004-08-31
PL188132B1 (pl) 2004-12-31
AU707653B2 (en) 1999-07-15
FI964317A (fi) 1996-10-25
LV11740B (en) 1997-12-20
EP0758341B1 (de) 2004-03-24
EE9600146A (et) 1997-04-15
LT4218B (en) 1997-09-25
FI964317A0 (fi) 1996-10-25
FI120494B (fi) 2009-11-13
KR100380124B1 (ko) 2003-08-02
IL113505A0 (en) 1995-07-31
ZA953361B (en) 1996-01-12
JPH10503477A (ja) 1998-03-31
ATE262536T1 (de) 2004-04-15
NO318759B1 (no) 2005-05-02
LT96151A (en) 1997-05-26
EP1384725A2 (de) 2004-01-28
DK0758341T3 (da) 2004-06-28
LV11740A (lv) 1997-04-20
CN1181091C (zh) 2004-12-22
CZ296439B6 (cs) 2006-03-15
HUT76346A (en) 1997-08-28
SI9520044A (en) 1997-10-31
CA2186497A1 (en) 1995-11-02
NO964553D0 (no) 1996-10-25
CA2186497C (en) 2008-06-17
JP3655632B2 (ja) 2005-06-02
EP1384725A3 (de) 2007-02-21
CZ314096A3 (en) 1997-05-14
SK136696A3 (en) 1997-05-07
SK286094B6 (sk) 2008-03-05
HU9602954D0 (en) 1996-12-30
NZ284977A (en) 1998-09-24
NO964553L (no) 1996-12-27
ES2214500T3 (es) 2004-09-16
PL317067A1 (en) 1997-03-03
PT758341E (pt) 2004-08-31
TW409129B (en) 2000-10-21
IL113505A (en) 1999-12-31
RU2152954C1 (ru) 2000-07-20
WO1995029189A1 (en) 1995-11-02
DE69532754T2 (de) 2005-03-10

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