CN1147504C - 新的凝血酶抑制剂,它们的制备和应用 - Google Patents

新的凝血酶抑制剂,它们的制备和应用

Info

Publication number
CN1147504C
CN1147504C CNB961967811A CN96196781A CN1147504C CN 1147504 C CN1147504 C CN 1147504C CN B961967811 A CNB961967811 A CN B961967811A CN 96196781 A CN96196781 A CN 96196781A CN 1147504 C CN1147504 C CN 1147504C
Authority
CN
China
Prior art keywords
pab
aze
nmr
prepared
compound
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
CNB961967811A
Other languages
English (en)
Chinese (zh)
Other versions
CN1195354A (zh
Inventor
D����ɭ
D·古斯塔夫森
��������ķ������
J·－E·奈斯特罗姆
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.)
AstraZeneca AB
Original Assignee
Astra AB
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 SE9502487A external-priority patent/SE9502487D0/xx
Priority claimed from SE9502505A external-priority patent/SE9502505D0/xx
Priority claimed from SE9502504A external-priority patent/SE9502504D0/xx
Priority claimed from SE9503923A external-priority patent/SE9503923D0/xx
Priority claimed from SE9504349A external-priority patent/SE9504349D0/xx
Priority claimed from GBGB9526411.5A external-priority patent/GB9526411D0/en
Application filed by Astra AB filed Critical Astra AB
Publication of CN1195354A publication Critical patent/CN1195354A/zh
Application granted granted Critical
Publication of CN1147504C publication Critical patent/CN1147504C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Plural Heterocyclic Compounds (AREA)
CNB961967811A 1995-07-06 1996-07-02 新的凝血酶抑制剂,它们的制备和应用 Expired - Fee Related CN1147504C (zh)

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
SE9502487A SE9502487D0 (sv) 1995-07-06 1995-07-06 New amino acid derivatives
SE95024873 1995-07-06
SE9502505A SE9502505D0 (sv) 1995-07-07 1995-07-07 New amino acid derivatives
SE95025045 1995-07-07
SE9502504A SE9502504D0 (sv) 1995-07-07 1995-07-07 New amino acid derivatives
SE95025052 1995-07-07
SE9503923A SE9503923D0 (sv) 1995-11-07 1995-11-07 New amino acid derivatives
SE95039236 1995-11-07
SE95043493 1995-12-05
SE9504349A SE9504349D0 (sv) 1995-12-05 1995-12-05 New amino acid derivatives
GBGB9526411.5A GB9526411D0 (en) 1995-12-22 1995-12-22 Compounds
GB9526411.5 1995-12-22

Publications (2)

Publication Number Publication Date
CN1195354A CN1195354A (zh) 1998-10-07
CN1147504C true CN1147504C (zh) 2004-04-28

Family

ID=27547251

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB961967811A Expired - Fee Related CN1147504C (zh) 1995-07-06 1996-07-02 新的凝血酶抑制剂,它们的制备和应用

Country Status (30)

Country Link
US (4) US6051568A (enExample)
EP (1) EP0836615B1 (enExample)
JP (1) JP4107682B2 (enExample)
KR (1) KR100435008B1 (enExample)
CN (1) CN1147504C (enExample)
AR (1) AR003440A1 (enExample)
AT (1) ATE238342T1 (enExample)
AU (1) AU709710B2 (enExample)
BR (1) BR9609447A (enExample)
CA (1) CA2226256C (enExample)
CZ (1) CZ298487B6 (enExample)
DE (1) DE69627659T2 (enExample)
DK (1) DK0836615T3 (enExample)
EE (1) EE04500B1 (enExample)
ES (1) ES2197240T3 (enExample)
HU (1) HUP9802315A3 (enExample)
IL (1) IL122813A0 (enExample)
IS (1) IS2081B (enExample)
MX (1) MX9800146A (enExample)
MY (1) MY116539A (enExample)
NO (1) NO324092B1 (enExample)
NZ (2) NZ311854A (enExample)
PL (1) PL185606B1 (enExample)
PT (1) PT836615E (enExample)
RU (1) RU2176645C2 (enExample)
SA (1) SA96170106A (enExample)
SI (1) SI0836615T1 (enExample)
SK (1) SK284695B6 (enExample)
TR (1) TR199800009T1 (enExample)
WO (1) WO1997002284A1 (enExample)

Families Citing this family (33)

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SA96170106A (ar) * 1995-07-06 2005-12-03 أسترا أكتيبولاج مشتقات حامض أميني جديدة
SE9602263D0 (sv) 1996-06-07 1996-06-07 Astra Ab New amino acid derivatives
JP2000514788A (ja) 1996-06-25 2000-11-07 イーライ・リリー・アンド・カンパニー 抗凝固剤
US6200967B1 (en) 1996-06-25 2001-03-13 Eli Lilly And Company Anticoagulant agents
SE9602646D0 (sv) 1996-07-04 1996-07-04 Astra Ab Pharmaceutically-useful compounds
AR013084A1 (es) 1997-06-19 2000-12-13 Astrazeneca Ab Derivados de amidino utiles como inhibidores de la trombina, composicion farmaceutica, utilizacion de dichos compuestos para la preparacion demedicamentos y proceso para la preparacion de los compuestos mencionados
SE9704543D0 (sv) * 1997-12-05 1997-12-05 Astra Ab New compounds
JP2003529528A (ja) 1998-04-24 2003-10-07 ３−ディメンショナル ファーマシューティカルズ， インコーポレイテッド プロテアーゼインヒビターとしてのアミノ酸アミジノヒドラゾン、アルコキシグアニジン、およびアミノグアニジン
SE9802938D0 (sv) * 1998-09-01 1998-09-01 Astra Ab Improved stability for injection solutions
WO2000031078A1 (en) * 1998-11-20 2000-06-02 Banyu Pharmaceutical Co., Ltd. 1-acylazetidine derivatives
SE9804313D0 (sv) 1998-12-14 1998-12-14 Astra Ab New compounds
KR20000047461A (ko) * 1998-12-29 2000-07-25 성재갑 트롬빈 억제제
WO2000042059A1 (en) * 1999-01-13 2000-07-20 Astrazeneca Ab New amidinobenzylamine derivatives and their use as thrombin inhibitors
AR023510A1 (es) 1999-04-21 2002-09-04 Astrazeneca Ab Un equipo de partes, formulacion farmaceutica y uso de un inhibidor de trombina.
SE0001803D0 (sv) 2000-05-16 2000-05-16 Astrazeneca Ab New compounds i
SI1311480T1 (sl) * 2000-08-16 2008-12-31 Astrazeneca Ab Novi amidino derivati in njihova uporaba kot trombinski inhibitorji
US6433186B1 (en) * 2000-08-16 2002-08-13 Astrazeneca Ab Amidino derivatives and their use as thormbin inhibitors
RU2300521C2 (ru) * 2000-12-01 2007-06-10 Астразенека Аб Новые производные миндальной кислоты и их применение в качестве ингибиторов тромбина
AR035216A1 (es) 2000-12-01 2004-05-05 Astrazeneca Ab Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios
SE0102921D0 (sv) * 2001-08-30 2001-08-30 Astrazeneca Ab Pharmaceutically useful compounds
US7129233B2 (en) * 2000-12-01 2006-10-31 Astrazeneca Ab Mandelic acid derivatives and their use as thrombin inhibitors
US6528503B2 (en) * 2000-12-18 2003-03-04 Merck & Co., Inc. Thrombin inhibitors
WO2002064559A2 (en) * 2001-02-09 2002-08-22 Merck & Co., Inc. Thrombin inhibitors
SE0101762D0 (sv) * 2001-05-18 2001-05-18 Astrazeneca Ab New use
AR034517A1 (es) * 2001-06-21 2004-02-25 Astrazeneca Ab Formulacion farmaceutica
UA78195C2 (uk) * 2001-08-30 2007-03-15 Astrazeneca Ab Похідні мигдалевої кислоти та їх застосування як інгібіторів тромбіну, фармацевтична композиція на їх основі
SE0201658D0 (sv) * 2002-05-31 2002-05-31 Astrazeneca Ab Immediate release pharmaceutical formulation
SE0201659D0 (sv) * 2002-05-31 2002-05-31 Astrazeneca Ab Modified release pharmaceutical formulation
SE0201661D0 (sv) 2002-05-31 2002-05-31 Astrazeneca Ab New salts
US7781424B2 (en) * 2003-05-27 2010-08-24 Astrazeneca Ab Modified release pharmaceutical formulation
US7524354B2 (en) * 2005-07-07 2009-04-28 Research Foundation Of State University Of New York Controlled synthesis of highly monodispersed gold nanoparticles
TW200827336A (en) * 2006-12-06 2008-07-01 Astrazeneca Ab New crystalline forms
US20090061000A1 (en) * 2007-08-31 2009-03-05 Astrazeneca Ab Pharmaceutical formulation use 030

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HU178398B (en) * 1979-06-12 1982-04-28 Gyogyszerkutato Intezet Process for producing new agmatine derivatives of activity against haemagglutination
ATE64956T1 (de) * 1984-06-14 1991-07-15 Ciba Geigy Ag Verfahren zur herstellung von thrombininhibitoren.
HU192646B (en) * 1984-12-21 1987-06-29 Gyogyszerkutato Intezet Process for preparing new n-alkyl-peptide aldehydes
CA1341029C (en) * 1985-02-04 2000-06-20 Michael Kolb Peptidase inhibitors
ZA883953B (en) * 1987-06-05 1990-02-28 Du Pont Peptide boronic acid inhibitors of trypsin-like proteases
US5187157A (en) * 1987-06-05 1993-02-16 Du Pont Merck Pharmaceutical Company Peptide boronic acid inhibitors of trypsin-like proteases
EP0362002B1 (en) * 1988-09-01 1995-07-26 Merrell Dow Pharmaceuticals Inc. HIV protease inhibitors
ZA897514B (en) * 1988-10-07 1990-06-27 Merrell Dow Pharma Novel peptidase inhibitors
CA2024697A1 (en) * 1989-09-07 1991-03-08 George P. Vlasuk Protein having anticoagulant properties
TW201303B (enExample) * 1990-07-05 1993-03-01 Hoffmann La Roche
IL99527A (en) * 1990-09-28 1997-08-14 Lilly Co Eli Tripeptide antithrombotic agents
CA2075154A1 (en) * 1991-08-06 1993-02-07 Neelakantan Balasubramanian Peptide aldehydes as antithrombotic agents
SE9102462D0 (sv) * 1991-08-28 1991-08-28 Astra Ab New isosteric peptides
RU2048719C1 (ru) * 1991-11-06 1995-11-27 Гкн Вальтершайд Гмбх Устройство для соединения сельскохозяйственного орудия с трактором
NZ245039A (en) * 1991-11-12 1994-12-22 Lilly Co Eli N-phenylalanyl and n-phenylglycyl derivatives of the dipeptide of l-azetidine-2-carboxylic acid and l-arginine aldehyde; anti-blood clotting compositions
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SE9103612D0 (sv) * 1991-12-04 1991-12-04 Astra Ab New peptide derivatives
WO1993018060A1 (en) * 1992-03-04 1993-09-16 Gyógyszerkutató Intézet Kft. New anticoagulant peptide derivatives and pharmaceutical compositions containing the same as well as a process for the preparation thereof
TW223629B (enExample) 1992-03-06 1994-05-11 Hoffmann La Roche
FR2695562B1 (fr) * 1992-09-11 1994-10-14 Synthelabo Utilisation d'un inhibiteur direct de la thrombine pour la fabrication d'un médicament à activité thrombolytique.
US5519193A (en) 1992-10-27 1996-05-21 International Business Machines Corporation Method and apparatus for stressing, burning in and reducing leakage current of electronic devices using microwave radiation
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AU675981B2 (en) * 1992-12-02 1997-02-27 Bristol-Myers Squibb Company Guanidinyl-substituted heterocyclic thrombin inhibitors
US5780631A (en) * 1993-06-03 1998-07-14 Astra Aktiebolag Starting materials in the synthesis of thrombin and kininogenase inhibitors
SE9301916D0 (sv) * 1993-06-03 1993-06-03 Ab Astra New peptides derivatives
DE4321444A1 (de) * 1993-06-28 1995-01-05 Bernd Prof Dr Clement Pharmazeutische Zubereitung
EP0648780A1 (en) * 1993-08-26 1995-04-19 Bristol-Myers Squibb Company Heterocyclic thrombin inhibitors
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US5726159A (en) * 1994-03-04 1998-03-10 Eli Lilly And Company Antithrombotic agents
US5705487A (en) * 1994-03-04 1998-01-06 Eli Lilly And Company Antithrombotic agents
US5707966A (en) * 1994-03-04 1998-01-13 Eli Lilly And Company Antithrombotic agents
US5561146A (en) * 1994-06-10 1996-10-01 Bristol-Myers Squibb Company Modified guanidino and amidino thrombin inhibitors
DE4421052A1 (de) * 1994-06-17 1995-12-21 Basf Ag Neue Thrombininhibitoren, ihre Herstellung und Verwendung
US5510369A (en) * 1994-07-22 1996-04-23 Merck & Co., Inc. Pyrrolidine thrombin inhibitors
FI972204A0 (fi) * 1994-11-24 1997-05-23 Janssen Pharmaceutica Nv Suonensisäisiä lubelutsoliliuoksia
KR100388185B1 (ko) * 1995-02-17 2003-11-28 애보트 게엠베하 운트 콤파니 카게 트롬빈 억제제로서의 신규 디펩티드 아미딘
US5710130A (en) * 1995-02-27 1998-01-20 Eli Lilly And Company Antithrombotic agents
US5629324A (en) 1995-04-10 1997-05-13 Merck & Co., Inc. Thrombin inhibitors
SA96170106A (ar) * 1995-07-06 2005-12-03 أسترا أكتيبولاج مشتقات حامض أميني جديدة
SE9602263D0 (sv) * 1996-06-07 1996-06-07 Astra Ab New amino acid derivatives

Also Published As

Publication number Publication date
NO980015L (no) 1998-02-25
IS4639A (is) 1997-12-22
US6617320B2 (en) 2003-09-09
CZ421297A3 (cs) 1998-06-17
IL122813A0 (en) 1998-08-16
US20040087647A1 (en) 2004-05-06
US6051568A (en) 2000-04-18
NZ311854A (en) 2000-06-23
HK1008995A1 (en) 1999-05-21
DE69627659T2 (de) 2004-03-04
JPH11508591A (ja) 1999-07-27
CA2226256A1 (en) 1997-01-23
DE69627659D1 (de) 2003-05-28
ATE238342T1 (de) 2003-05-15
AU709710B2 (en) 1999-09-02
NO980015D0 (no) 1998-01-02
SA96170106A (ar) 2005-12-03
PL324483A1 (en) 1998-05-25
MY116539A (en) 2004-02-28
CN1195354A (zh) 1998-10-07
EP0836615A1 (en) 1998-04-22
SI0836615T1 (en) 2003-10-31
EE9700354A (et) 1998-06-15
PL185606B1 (pl) 2003-06-30
NZ509474A (en) 2005-08-26
JP4107682B2 (ja) 2008-06-25
TR199800009T1 (xx) 1998-05-21
US20020042396A1 (en) 2002-04-11
EP0836615B1 (en) 2003-04-23
KR19990028755A (ko) 1999-04-15
AR003440A1 (es) 1998-08-05
KR100435008B1 (ko) 2004-07-16
HUP9802315A3 (en) 1999-03-01
IS2081B (is) 2006-02-15
HUP9802315A2 (hu) 1999-01-28
ES2197240T3 (es) 2004-01-01
DK0836615T3 (da) 2003-08-11
EE04500B1 (et) 2005-06-15
AU6325396A (en) 1997-02-05
US6921758B2 (en) 2005-07-26
RU2176645C2 (ru) 2001-12-10
US6337343B1 (en) 2002-01-08
NO324092B1 (no) 2007-08-13
BR9609447A (pt) 1999-03-02
CZ298487B6 (cs) 2007-10-17
PT836615E (pt) 2003-09-30
SK180497A3 (en) 1998-11-04
MX9800146A (es) 1998-03-31
CA2226256C (en) 2008-12-30
SK284695B6 (sk) 2005-09-08
WO1997002284A1 (en) 1997-01-23

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Granted publication date: 20040428

Termination date: 20100702