NO328523B1 - Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat. - Google Patents

Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat. Download PDF

Info

Publication number: NO328523B1
Authority: NO; Norway
Prior art keywords: paph; alloc; glu; compound; cha
Prior art date: 1998-09-15

Application number

NO20011293A

Other languages

English (en)

Norwegian (no)

Other versions

NO20011293L (no

NO20011293D0 (no

Inventor

Pavel Safar

Peter Wildgoose

Alena Safarova

Original Assignee

Sanofi Aventis Deutschland

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.)

1998-09-15

Filing date

2001-03-14

Publication date

2010-03-08

2001-03-14 Application filed by Sanofi Aventis Deutschland filed Critical Sanofi Aventis Deutschland

2001-03-14 Publication of NO20011293D0 publication Critical patent/NO20011293D0/no

2001-05-04 Publication of NO20011293L publication Critical patent/NO20011293L/no

2010-03-08 Publication of NO328523B1 publication Critical patent/NO328523B1/no

Links

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IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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125000001302 tertiary amino group Chemical group 0.000 description 1
CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical class CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
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230000001732 thrombotic effect Effects 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
238000011541 total hip replacement Methods 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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239000000080 wetting agent Substances 0.000 description 1
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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
- 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
- C07K5/1019—Tetrapeptides with the first amino acid being basic
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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
- 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/105831—Protein or peptide standard or control [e.g., hemoglobin, etc.]

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Biophysics (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
Cardiology (AREA)
Hematology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO20011293A 1998-09-15 2001-03-14 Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat. NO328523B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP98117506A EP0987274A1 (de)	1998-09-15	1998-09-15	Faktor VIIa Inhibitore
PCT/EP1999/006449 WO2000015658A1 (en)	1998-09-15	1999-09-02	FACTOR VIIa INHIBITORS

Publications (3)

Publication Number	Publication Date
NO20011293D0 NO20011293D0 (no)	2001-03-14
NO20011293L NO20011293L (no)	2001-05-04
NO328523B1 true NO328523B1 (no)	2010-03-08

Family

ID=8232644

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20011293A NO328523B1 (no)	1998-09-15	2001-03-14	Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat.

Country Status (25)

Country	Link
US (1)	US6287794B1 (de)
EP (2)	EP0987274A1 (de)
JP (1)	JP4537581B2 (de)
KR (1)	KR100665490B1 (de)
CN (1)	CN1203087C (de)
AR (1)	AR027814A1 (de)
AT (1)	ATE460424T1 (de)
AU (1)	AU760580B2 (de)
BR (1)	BR9913742A (de)
CA (1)	CA2344048A1 (de)
CZ (1)	CZ300249B6 (de)
DE (1)	DE69942123D1 (de)
HK (1)	HK1040253B (de)
HU (1)	HUP0103851A3 (de)
ID (1)	ID28494A (de)
IL (2)	IL141415A0 (de)
MY (1)	MY125150A (de)
NO (1)	NO328523B1 (de)
NZ (1)	NZ510509A (de)
PL (1)	PL203227B1 (de)
RU (1)	RU2223967C2 (de)
TR (1)	TR200100766T2 (de)
TW (1)	TW576839B (de)
WO (1)	WO2000015658A1 (de)
ZA (1)	ZA200101861B (de)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0987274A1 (de) *	1998-09-15	2000-03-22	Hoechst Marion Roussel Deutschland GmbH	Faktor VIIa Inhibitore
EP1144373B1 (de)	1999-01-13	2005-10-19	Genentech, Inc.	Serinprotease-inhibitoren
EP1059302A1 (de) *	1999-06-08	2000-12-13	Aventis Pharma Deutschland GmbH	Faktor VIIa Inhibitore
DK1222854T3 (da) *	1999-10-01	2011-03-14	Chugai Pharmaceutical Co Ltd	Forebyggelse og behandling af sygdomme forbundet med blodkoagulering
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
EP1162194A1 (de) *	2000-06-06	2001-12-12	Aventis Pharma Deutschland GmbH	Auf Faktor VIIa inhibitorisch wirkende (Thio)-Harnstoff Verbindungen, Verfahren zu deren Herstellung und deren Verwendung
GB0014134D0 (en) *	2000-06-10	2000-08-02	Astrazeneca Ab	Combination therapy
CA2426430C (en)	2000-10-20	2014-10-07	Biocryst Pharmaceuticals, Inc.	Biaryl compounds as serine protease inhibitors
PL362320A1 (en)	2000-12-06	2004-10-18	Aventis Pharma Deutschland Gmbh	Guanidine and amidine derivatives as factor xa inhibitors
JP4179878B2 (ja)	2001-02-02	2008-11-12	中外製薬株式会社	ペプチド誘導体
EP1270551A1 (de)	2001-06-26	2003-01-02	Aventis Pharma Deutschland GmbH	Harnstoffverbindungen mit antiproteolytischer Wirkung
EP1314733A1 (de)	2001-11-22	2003-05-28	Aventis Pharma Deutschland GmbH	Indol-2-carbonsäureamide als Faktor-Xa-Hemmer
US7604932B2 (en) *	2002-11-13	2009-10-20	Haematologic Technologies, Inc.	Assay for tissue factor in a sample
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
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
EP1479677A1 (de) *	2003-05-19	2004-11-24	Aventis Pharma Deutschland GmbH	Neue Indolderivate als Faktor Xa-Inhibitoren
US7741341B2 (en)	2003-05-19	2010-06-22	Sanofi-Aventis Deutschland Gmbh	Benzimidazole-derivatives as factor Xa inhibitors
EP1479680A1 (de)	2003-05-19	2004-11-24	Aventis Pharma Deutschland GmbH	Azaindole-Derivative als Faktor Xa Hemmer
US7317027B2 (en)	2003-05-19	2008-01-08	Sanofi-Aventis Deutschland Gmbh	Azaindole-derivatives as factor Xa inhibitors
CA2525713A1 (en)	2003-05-20	2004-12-29	Genentech, Inc.	Benzofuran inhibitors of factor viia
WO2004113278A2 (en)	2003-05-20	2004-12-29	Genentech, Inc.	Acylsulfamide inhibitors of factor viia
EP1568698A1 (de)	2004-02-27	2005-08-31	Aventis Pharma Deutschland GmbH	Pyrrolderivate als faktor-xa-inhibitoren
ES2399277T3 (es) *	2004-05-27	2013-03-27	Baxter International Inc.	Procedimiento de tratamiento de trastornos hemorrágicos utilizando polisacáridos sulfatados
WO2008107362A2 (en) *	2007-03-07	2008-09-12	Novo Nordisk Health Care Ag	Stabiliser and inhibitors of factor vii
KR20100031732A (ko)	2007-07-10	2010-03-24	사노피-아벤티스	항혈전 활성을 갖는 말론아미드 유도체
WO2009092758A1 (en) *	2008-01-23	2009-07-30	Novo Nordisk Health Care Ag	New blood coagulation factor inhibitors
CN103561758B (zh)	2011-02-04	2017-06-16	奥克塔法马股份有限公司	通过沉降灭活/去除凝血因子的方法
JP2022500463A (ja) *	2018-09-11	2022-01-04	アンビションソチエタレスポンサビリタリミタータ	ペプチドおよびその医学的使用
WO2020053772A1 (en) *	2018-09-11	2020-03-19	Anbition S.R.L.	Peptides and medical uses thereof
RS66218B1 (sr)	2019-07-01	2024-12-31	Tonix Pharma Ltd	Anti-cd154 antitela i njihove upotrebe
WO2022150452A1 (en)	2021-01-06	2022-07-14	Seth Lederman	Methods of inducing immune tolerance with modified anti-cd154 antibodies
GB202209228D0 (en) *	2022-06-23	2022-08-10	Univ Strathclyde	Modified amino acids and uses thereof
WO2025248134A1 (en)	2024-05-31	2025-12-04	Tonix Pharma Limited	Treatment methods comprising administration of modified cd154 antibodies

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5023236A (en) *	1988-04-07	1991-06-11	Corvas, Inc.	Factor VII/VIIA active site inhibitors
AU4338689A (en) *	1988-09-23	1990-04-18	Corvas, Inc.	Peptidyl inhibitors of the initiation of coagulation
CA2008116C (en) *	1989-02-23	2001-11-20	Thomas Weller	Glycine derivatives
US5190919A (en) *	1989-11-13	1993-03-02	Board Of Regents, The University Of Texas System	Antihemostatic factor vii peptides
HU206372B (en) *	1990-09-03	1992-10-28	Richter Gedeon Vegyeszet	Process for producing new oligopeptides which selectively inhibit proliferation of haemopoietic cells and pharmaceutical compositions comprising same
US5506134A (en)	1990-10-22	1996-04-09	Corvas International, Inc.	Hypridoma and monoclonal antibody which inhibits blood coagulation tissue factor/factor VIIa complex
US5833982A (en)	1991-02-28	1998-11-10	Zymogenetics, Inc.	Modified factor VII
US5788965A (en)	1991-02-28	1998-08-04	Novo Nordisk A/S	Modified factor VII
SE9301916D0 (sv) *	1993-06-03	1993-06-03	Ab Astra	New peptides derivatives
DK0703923T3 (da) *	1993-06-18	1999-06-21	Nycomed Imaging As	Faktor VII afledte peptider
EP1384725A3 (de) *	1994-04-26	2007-02-21	Aventis Pharmaceuticals Inc.	Inhibitoren von Faktor Xa
US5849510A (en) *	1994-04-26	1998-12-15	Selectide Corporation	Factor Xa inhibitors
RU2097033C1 (ru) *	1994-09-30	1997-11-27	Московская государственная академия тонкой химической технологии им.М.В.Ломоносова	Имидазолсодержащие ингибиторы катепсин g-индуцированной агрегации тромбоцитов
US5837684A (en) *	1995-06-07	1998-11-17	Nycomed Imaging As	Peptides
PT892780E (pt) *	1996-02-22	2003-02-28	Bristol Myers Squibb Pharma Co	Analogos de m-amidino fenilo como inibidores do factor xa
EP0987274A1 (de) *	1998-09-15	2000-03-22	Hoechst Marion Roussel Deutschland GmbH	Faktor VIIa Inhibitore

1998
- 1998-09-15 EP EP98117506A patent/EP0987274A1/de not_active Withdrawn
1999
- 1999-09-02 CA CA002344048A patent/CA2344048A1/en not_active Abandoned
- 1999-09-02 HK HK02101586.6A patent/HK1040253B/zh not_active IP Right Cessation
- 1999-09-02 AU AU59723/99A patent/AU760580B2/en not_active Ceased
- 1999-09-02 WO PCT/EP1999/006449 patent/WO2000015658A1/en not_active Ceased
- 1999-09-02 BR BR9913742-9A patent/BR9913742A/pt not_active Application Discontinuation
- 1999-09-02 NZ NZ510509A patent/NZ510509A/xx not_active IP Right Cessation
- 1999-09-02 TR TR2001/00766T patent/TR200100766T2/xx unknown
- 1999-09-02 ID IDW20010598A patent/ID28494A/id unknown
- 1999-09-02 KR KR1020017003350A patent/KR100665490B1/ko not_active Expired - Fee Related
- 1999-09-02 PL PL346781A patent/PL203227B1/pl not_active IP Right Cessation
- 1999-09-02 DE DE69942123T patent/DE69942123D1/de not_active Expired - Lifetime
- 1999-09-02 JP JP2000570196A patent/JP4537581B2/ja not_active Expired - Fee Related
- 1999-09-02 AT AT99969095T patent/ATE460424T1/de not_active IP Right Cessation
- 1999-09-02 CN CNB998109169A patent/CN1203087C/zh not_active Expired - Fee Related
- 1999-09-02 CZ CZ20010914A patent/CZ300249B6/cs not_active IP Right Cessation
- 1999-09-02 IL IL14141599A patent/IL141415A0/xx active IP Right Grant
- 1999-09-02 EP EP99969095A patent/EP1114061B1/de not_active Expired - Lifetime
- 1999-09-02 RU RU2001110086/04A patent/RU2223967C2/ru not_active IP Right Cessation
- 1999-09-02 HU HU0103851A patent/HUP0103851A3/hu unknown
- 1999-09-13 AR ARP990104586A patent/AR027814A1/es active IP Right Grant
- 1999-09-14 US US09/395,572 patent/US6287794B1/en not_active Expired - Lifetime
- 1999-09-14 MY MYPI99003984A patent/MY125150A/en unknown
- 1999-09-20 TW TW088115707A patent/TW576839B/zh active
2001
- 2001-02-13 IL IL141415A patent/IL141415A/en not_active IP Right Cessation
- 2001-03-06 ZA ZA200101861A patent/ZA200101861B/en unknown
- 2001-03-14 NO NO20011293A patent/NO328523B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
IL141415A0 (en)	2002-03-10
HUP0103851A2 (hu)	2002-04-29
NO20011293L (no)	2001-05-04
CZ2001914A3 (en)	2001-06-13
HK1040253A1 (en)	2002-05-31
HK1040253B (zh)	2005-09-02
EP0987274A1 (de)	2000-03-22
ATE460424T1 (de)	2010-03-15
ID28494A (id)	2001-05-31
CA2344048A1 (en)	2000-03-23
US6287794B1 (en)	2001-09-11
JP4537581B2 (ja)	2010-09-01
KR20010075130A (ko)	2001-08-09
HUP0103851A3 (en)	2002-05-28
CN1318069A (zh)	2001-10-17
EP1114061B1 (de)	2010-03-10
AU760580B2 (en)	2003-05-15
CZ300249B6 (cs)	2009-04-01
TW576839B (en)	2004-02-21
ZA200101861B (en)	2001-10-22
NO20011293D0 (no)	2001-03-14
BR9913742A (pt)	2001-06-05
KR100665490B1 (ko)	2007-01-10
TR200100766T2 (tr)	2001-10-22
IL141415A (en)	2006-09-05
EP1114061A1 (de)	2001-07-11
PL346781A1 (en)	2002-02-25
PL203227B1 (pl)	2009-09-30
RU2223967C2 (ru)	2004-02-20
NZ510509A (en)	2002-09-27
JP2002524571A (ja)	2002-08-06
DE69942123D1 (de)	2010-04-22
MY125150A (en)	2006-07-31
WO2000015658A1 (en)	2000-03-23
AU5972399A (en)	2000-04-03
CN1203087C (zh)	2005-05-25
AR027814A1 (es)	2003-04-16

Legal Events

Date	Code	Title	Description
2011-05-09	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO328523B1 (no)	2010-03-08	Faktor VIIa-inhibitorer, fremgangsmate for fremstilling av slike og farmasoytisk preparat omfattende slike, samt anvendelse av inhibitorene for fremstilling av farmasoytisk preparat.
EP0699074B1 (de)	2002-11-13	Thrombin-inhibitoren
US5672582A (en)	1997-09-30	Thrombin inhibitors
US5597804A (en)	1997-01-28	N-sulfonylarginine keto-amide compounds
AU601801B2 (en)	1990-09-20	Anticoagulant peptides
JPH08508716A (ja)	1996-09-17	血栓症のインヒビター
JPH10503477A (ja)	1998-03-31	第Ｘａ因子インヒビター
EP0482080A1 (de)	1992-04-29	Kleine zyklische blutplättcheninhibitoren.
KR19980703173A (ko)	1998-10-15	히루딘의 아미노산 서열에 기초한 트롬빈 억제제
HRP20010912A2 (en)	2003-04-30	FACTOR VIIa INHIBITORS
RU2175327C2 (ru)	2001-10-27	Производные имидазо[1,5-а]пиридина как ингибиторы серинпротеаз и фармацевтическая композиция
US7879792B2 (en)	2011-02-01	Synthetic peptide inhibitors of thrombin and thrombin activation of protease activated receptors 1 and 4
US5856309A (en)	1999-01-05	Amidinopyrroline derivatives, processes for their production and pharmaceutical agents containing these compounds
MXPA01002400A (en)	2001-11-21	FACTOR VIIa INHIBITORS
EP1425009A2 (de)	2004-06-09	Peptid-arginale und verfahren zur behandlung der disseminierten intravaskulären koagulation
AU2002331654A1 (en)	2003-05-29	Peptide arginals and methods for treating disseminated intravascular coagulation
NO300504B1 (no)	1997-06-09	Forbindelse og terapeutisk preparat omfattende denne
HK1009454B (en)	2001-04-27	Imidazo(1.5a) pyridine derived serine protease inhibitors