WO2000061609A3 - Prodrugs von thrombininhibitoren - Google Patents

Prodrugs von thrombininhibitoren Download PDF

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Publication number
WO2000061609A3
WO2000061609A3 PCT/EP2000/003009 EP0003009W WO0061609A3 WO 2000061609 A3 WO2000061609 A3 WO 2000061609A3 EP 0003009 W EP0003009 W EP 0003009W WO 0061609 A3 WO0061609 A3 WO 0061609A3
Authority
WO
WIPO (PCT)
Prior art keywords
prodrugs
compounds
thrombin inhibitors
relates
thrombin
Prior art date
Application number
PCT/EP2000/003009
Other languages
English (en)
French (fr)
Other versions
WO2000061609A2 (de
WO2000061609B1 (de
Inventor
Dorit Baucke
Helmut Mack
Werner Seitz
Wilfried Hornberger
Gisela Backfisch
Juergen DELZER
Original Assignee
Basf Ag
Dorit Baucke
Helmut Mack
Werner Seitz
Wilfried Hornberger
Gisela Backfisch
Juergen DELZER
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 to CA002370267A priority Critical patent/CA2370267A1/en
Priority to NZ515026A priority patent/NZ515026A/en
Priority to JP2000611551A priority patent/JP2002542165A/ja
Priority to AU41156/00A priority patent/AU765244B2/en
Priority to PL00352824A priority patent/PL352824A1/xx
Priority to IL14577200A priority patent/IL145772A0/xx
Priority to KR1020017012870A priority patent/KR20010108481A/ko
Priority to BR0009674-1A priority patent/BR0009674A/pt
Application filed by Basf Ag, Dorit Baucke, Helmut Mack, Werner Seitz, Wilfried Hornberger, Gisela Backfisch, Juergen DELZER filed Critical Basf Ag
Priority to US09/958,349 priority patent/US7144902B1/en
Priority to EP00920661A priority patent/EP1165601A2/de
Priority to SK1422-2001A priority patent/SK14222001A3/sk
Publication of WO2000061609A2 publication Critical patent/WO2000061609A2/de
Publication of WO2000061609A3 publication Critical patent/WO2000061609A3/de
Publication of WO2000061609B1 publication Critical patent/WO2000061609B1/de
Priority to BG105986A priority patent/BG105986A/bg
Priority to NO20014875A priority patent/NO20014875L/no
Priority to HK02107849.6A priority patent/HK1046289A1/zh

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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B43/00—Formation or introduction of functional groups containing nitrogen
    • 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
    • C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
    • C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

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

Abstract

Die vorliegende Erfindung betrifft Prodrugs von pharmakologisch wirksamen, fünfgliedrigen heterocyclischen Amidinen, aus denen in vivo Verbindungen entstehen, welche kompetitive Inhibitoren von Trypsin-ähnlichen Serinproteasen, besonders Thrombin und Kininogenasen wie Kallikrein sind, ihre Herstellung und ihre Verwendung als Medikamente. Die Erfindung bezieht sich auch auf pharmazeutische Zusammensetzungen, die die Prodrugs der aktiven Verbindungen als Bestandteile enthalten, sowie die Verwendung der Verbindungen als Thrombininhibitoren, Antikoagulantien und als antiinflammatorische Agenzien.
PCT/EP2000/003009 1999-04-09 2000-04-05 Prodrugs von thrombininhibitoren WO2000061609A2 (de)

Priority Applications (14)

Application Number Priority Date Filing Date Title
US09/958,349 US7144902B1 (en) 1999-04-09 2000-04-05 Prodrugs of thrombin inhibitors
NZ515026A NZ515026A (en) 1999-04-09 2000-04-05 Heterocyclic amidine derivatives useful as prodrugs of thrombin inhibitors
EP00920661A EP1165601A2 (de) 1999-04-09 2000-04-05 Prodrugs von thrombininhibitoren
PL00352824A PL352824A1 (en) 1999-04-09 2000-04-05 Prodrugs of thrombin inhibitors
IL14577200A IL145772A0 (en) 1999-04-09 2000-04-05 Prodrugs of thrombin inhibitors
KR1020017012870A KR20010108481A (ko) 1999-04-09 2000-04-05 트롬빈 억제제의 프로드럭
BR0009674-1A BR0009674A (pt) 1999-04-09 2000-04-05 Composto, droga, e, uso de composto
CA002370267A CA2370267A1 (en) 1999-04-09 2000-04-05 Prodrugs of thrombin inhibitors
JP2000611551A JP2002542165A (ja) 1999-04-09 2000-04-05 トロンビンインヒビターのプロドラッグ
AU41156/00A AU765244B2 (en) 1999-04-09 2000-04-05 Prodrugs of thrombin inhibitors
SK1422-2001A SK14222001A3 (sk) 1999-04-09 2000-04-05 Prekurzory trombínových inhibítorov
BG105986A BG105986A (bg) 1999-04-09 2001-10-05 Пролекарства на тромбинови инхибитори
NO20014875A NO20014875L (no) 1999-04-09 2001-10-08 Promedikamenter for trombin inhibitorer
HK02107849.6A HK1046289A1 (zh) 1999-04-09 2002-10-30 凝血酶抑制劑的前體藥物

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
DE19915930.0 1999-04-09
DE19915930 1999-04-09
DE19934123.0 1999-07-23
DE19934123 1999-07-23
DE19947920.8 1999-10-06
DE19947920 1999-10-06

Publications (3)

Publication Number Publication Date
WO2000061609A2 WO2000061609A2 (de) 2000-10-19
WO2000061609A3 true WO2000061609A3 (de) 2001-03-15
WO2000061609B1 WO2000061609B1 (de) 2001-04-26

Family

ID=27219075

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/003009 WO2000061609A2 (de) 1999-04-09 2000-04-05 Prodrugs von thrombininhibitoren

Country Status (18)

Country Link
US (1) US7144902B1 (de)
EP (1) EP1165601A2 (de)
JP (1) JP2002542165A (de)
KR (1) KR20010108481A (de)
CN (1) CN1355810A (de)
AU (1) AU765244B2 (de)
BG (1) BG105986A (de)
BR (1) BR0009674A (de)
CA (1) CA2370267A1 (de)
HK (1) HK1046289A1 (de)
HU (1) HUP0202401A3 (de)
IL (1) IL145772A0 (de)
NO (1) NO20014875L (de)
NZ (1) NZ515026A (de)
PL (1) PL352824A1 (de)
SK (1) SK14222001A3 (de)
TR (1) TR200102912T2 (de)
WO (1) WO2000061609A2 (de)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10064797A1 (de) * 2000-12-22 2002-06-27 Knoll Ag Orale und parenterale pharmazeutische Formulierung, umfassend eine niedermolekulare Thrombininhibitor-Pro-Pharmakon
WO2004002985A1 (en) * 2002-06-27 2004-01-08 Lg Life Sciences Ltd. Peptidic thrombin inhibitor compound
AU2004239468B2 (en) * 2003-05-16 2009-09-10 National Institute For Biological Standards And Control (Nibsc) Activation mixture
DE602005023429D1 (de) 2004-10-19 2010-10-21 Lonza Ag Verfahren zur festphasen-peptidsynthese
WO2006117567A2 (en) * 2005-05-05 2006-11-09 Chroma Therapeutics Ltd Alpha aminoacid ester-drug conjugates hydrolysable by carboxylesterase
ME02461B (me) 2005-05-10 2017-02-20 Incyte Holdings Corp Modulatori indoleamina 2,3-dioksigenaze i metode za upotrebu istih
ES2540561T3 (es) 2005-12-20 2015-07-10 Incyte Corporation N-hidroxiamidinoheterociclos como moduladores de indolamina 2,3-dioxigenasa
CL2007002650A1 (es) 2006-09-19 2008-02-08 Incyte Corp Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras.
CA2663057C (en) 2006-09-19 2015-12-08 Incyte Corporation N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase
MY171866A (en) 2008-07-08 2019-11-05 Incyte Holdings Corp 1,2,5-oxadiazoles as inhibitors of indoleamine 2,3-dioxygenase
EP2512466A4 (de) 2009-12-18 2013-07-03 Activesite Pharmaceuticals Inc Prodrugs von plasmakallikreinhemmern
US9206123B2 (en) 2009-12-18 2015-12-08 Activesite Pharmaceuticals, Inc. Prodrugs of inhibitors of plasma kallikrein
EP2697196A1 (de) 2011-04-13 2014-02-19 Activesite Pharmaceuticals, Inc. Prodrugs von plasmakallikreinhemmern
PL3066085T3 (pl) 2013-11-08 2020-11-02 Incyte Holdings Corporation Sposób syntezy inhibitora 2,3-dioksygenazy indoloaminowej
EP3187497A4 (de) * 2014-08-26 2018-02-07 Takeda Pharmaceutical Company Limited Heterocyclische verbindung
CN106674190B (zh) * 2016-12-13 2019-05-10 台州市创源工业技术有限公司 一种2-噻吩甲胺的合成方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0672658A1 (de) * 1994-03-04 1995-09-20 Eli Lilly And Company Verbindungen zur Hemmung der Thrombin
WO1997023499A1 (en) * 1995-12-21 1997-07-03 Astra Aktiebolag Prodrugs of thrombin inhibitors
DE19632773A1 (de) * 1996-08-14 1998-02-19 Basf Ag Neue Thrombininhibitoren
WO1999037668A1 (de) * 1998-01-26 1999-07-29 Basf Aktiengesellschaft Thrombininhibitoren
WO1999037611A1 (de) * 1998-01-26 1999-07-29 Basf Aktiengesellschaft Heterocyclische amidine als kallikrein protease inhibitoren

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW523513B (en) 1996-03-01 2003-03-11 Akzo Nobel Nv Serine protease inhibitors
KR20000047461A (ko) * 1998-12-29 2000-07-25 성재갑 트롬빈 억제제
WO2000061608A2 (de) * 1999-04-09 2000-10-19 Basf Aktiengesellschaft Niedermolekulare inhibitoren von komplementproteasen

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0672658A1 (de) * 1994-03-04 1995-09-20 Eli Lilly And Company Verbindungen zur Hemmung der Thrombin
WO1997023499A1 (en) * 1995-12-21 1997-07-03 Astra Aktiebolag Prodrugs of thrombin inhibitors
DE19632773A1 (de) * 1996-08-14 1998-02-19 Basf Ag Neue Thrombininhibitoren
WO1999037668A1 (de) * 1998-01-26 1999-07-29 Basf Aktiengesellschaft Thrombininhibitoren
WO1999037611A1 (de) * 1998-01-26 1999-07-29 Basf Aktiengesellschaft Heterocyclische amidine als kallikrein protease inhibitoren

Also Published As

Publication number Publication date
AU765244B2 (en) 2003-09-11
JP2002542165A (ja) 2002-12-10
US7144902B1 (en) 2006-12-05
AU4115600A (en) 2000-11-14
HUP0202401A3 (en) 2003-11-28
BG105986A (bg) 2002-06-28
HK1046289A1 (zh) 2003-01-03
TR200102912T2 (tr) 2002-03-21
WO2000061609A2 (de) 2000-10-19
SK14222001A3 (sk) 2002-07-02
HUP0202401A2 (en) 2002-10-28
PL352824A1 (en) 2003-09-08
NO20014875L (no) 2001-11-13
BR0009674A (pt) 2002-01-15
CA2370267A1 (en) 2000-10-19
IL145772A0 (en) 2002-07-25
NO20014875D0 (no) 2001-10-08
EP1165601A2 (de) 2002-01-02
NZ515026A (en) 2003-10-31
KR20010108481A (ko) 2001-12-07
CN1355810A (zh) 2002-06-26
WO2000061609B1 (de) 2001-04-26

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