CN103403018B - 胰蛋白酶样丝氨酸蛋白酶抑制剂,它们的制备以及作为凝结因子IIa和Xa的选择性抑制剂的用途 - Google Patents

胰蛋白酶样丝氨酸蛋白酶抑制剂,它们的制备以及作为凝结因子IIa和Xa的选择性抑制剂的用途 Download PDF

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CN103403018B
CN103403018B CN201180065191.4A CN201180065191A CN103403018B CN 103403018 B CN103403018 B CN 103403018B CN 201180065191 A CN201180065191 A CN 201180065191A CN 103403018 B CN103403018 B CN 103403018B
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CN103403018A (zh
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P·哈罗德
S·杰拉科维奇克
M·达基施
C·里彻尔特
A·舒尔茨
A·施维尼茨
F-A·路德维格
A·R·法
T·康
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Pharmaceutical Co (leipzig) Ltd
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    • 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
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C07K5/06113—Asp- or Asn-amino acid
    • C07K5/06121—Asp- or Asn-amino acid the second amino acid being aromatic or cycloaliphatic
    • 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
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • 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
    • C07K5/06—Dipeptides
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • 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
    • C07K5/06104—Dipeptides with the first amino acid being acidic
    • C07K5/06113—Asp- or Asn-amino acid
    • 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
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
CN201180065191.4A 2010-12-21 2011-12-21 胰蛋白酶样丝氨酸蛋白酶抑制剂,它们的制备以及作为凝结因子IIa和Xa的选择性抑制剂的用途 Expired - Fee Related CN103403018B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201061425597P 2010-12-21 2010-12-21
US61/425,597 2010-12-21
PCT/CA2011/001398 WO2012083436A1 (en) 2010-12-21 2011-12-21 Trypsin-like serine protease inhibitors, their preparation and use as selective inhibitors of the clotting factors iia and xa

Publications (2)

Publication Number Publication Date
CN103403018A CN103403018A (zh) 2013-11-20
CN103403018B true CN103403018B (zh) 2015-08-19

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CN201180065191.4A Expired - Fee Related CN103403018B (zh) 2010-12-21 2011-12-21 胰蛋白酶样丝氨酸蛋白酶抑制剂,它们的制备以及作为凝结因子IIa和Xa的选择性抑制剂的用途

Country Status (9)

Country Link
US (1) US8497245B2 (enExample)
EP (1) EP2655399B1 (enExample)
JP (1) JP5923110B2 (enExample)
CN (1) CN103403018B (enExample)
AU (1) AU2011349022B2 (enExample)
CA (1) CA2822350A1 (enExample)
ES (1) ES2654440T3 (enExample)
NO (1) NO2655399T3 (enExample)
WO (1) WO2012083436A1 (enExample)

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DE10301300B4 (de) 2003-01-15 2009-07-16 Curacyte Chemistry Gmbh Verwendung von acylierten 4-Amidino- und 4-Guanidinobenzylaminen zur Inhibierung von Plasmakallikrein
EP2590945B1 (en) 2010-07-07 2014-04-30 The Medicines Company (Leipzig) GmbH Serine protease inhibitors
GB201311888D0 (en) * 2013-07-03 2013-08-14 Glaxosmithkline Ip Dev Ltd Novel compounds
AU2017257267B2 (en) * 2016-04-25 2020-05-14 Instrumentation Laboratory Company Method and kit for identifying lupus anticoagulant (LA) associated with antiphospholipid syndrome
US11014920B2 (en) 2016-11-18 2021-05-25 Merck Sharp & Dohme Corp. Factor XIIa inhibitors
GB201805174D0 (en) * 2018-03-29 2018-05-16 Univ Leeds Innovations Ltd Compounds
GB201807014D0 (en) * 2018-04-30 2018-06-13 Univ Leeds Innovations Ltd Factor xlla inhibitors
US20220204497A1 (en) * 2019-03-29 2022-06-30 Medicinal Bioconvergence Research Center Novel compound having anticancer activity, and method for producing same

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WO1994017817A1 (en) * 1993-02-12 1994-08-18 Corvas International, Inc. Inhibitors of thrombosis
CN1121068A (zh) * 1994-01-27 1996-04-24 三菱化学株式会社 脯氨酰胺衍生物
CN1147205A (zh) * 1994-03-04 1997-04-09 伊莱利利公司 抗血栓形成剂
US5955576A (en) * 1992-02-14 1999-09-21 Corvas International, Inc. Inhibitors of thrombosis

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DE3163469D1 (en) * 1980-05-12 1984-06-14 Choay Sa Oligopeptides with specific inhibiting properties of collagen induced aggregation, process for preparing the same and pharmaceutical compositions containing them
CA1241120A (en) 1985-10-01 1988-08-23 Sami A. Aly Alternate mark inversion (ami) receiver
EP0648780A1 (en) * 1993-08-26 1995-04-19 Bristol-Myers Squibb Company Heterocyclic thrombin inhibitors
JPH07138298A (ja) * 1993-11-19 1995-05-30 Japan Energy Corp ヒルジン類縁体硫酸エステル化体またはその塩の製造方法
US5914319A (en) * 1995-02-27 1999-06-22 Eli Lilly And Company Antithrombotic agents
US6255286B1 (en) * 1996-06-25 2001-07-03 Nisshin Flour Milling Co., Ltd. Depsipeptides and drugs containing the same as the active ingredient
BR9815325A (pt) 1997-11-26 2001-12-26 Dimensional Pharm Inc Heteroaril, aminoguanidinas e alcóxiguanidinas eseu uso como inibidores da protease
DE10029014A1 (de) 2000-06-15 2001-12-20 Univ Schiller Jena Urokinase-Hemmstoffe
DE10029015A1 (de) 2000-06-15 2001-12-20 Curacyte Ag Hemmstoffe für den Gerinnungsfaktor Xa
JP2004516286A (ja) 2000-12-18 2004-06-03 メルク エンド カムパニー インコーポレーテッド ベンジルアミン誘導体およびそれのトロンビン阻害薬としての使用
DE10102878A1 (de) * 2001-01-23 2002-08-01 Haemosys Gmbh Oligo- oder Polyalkylengekoppelte Thrombininhibitoren
ATE399175T1 (de) 2002-03-11 2008-07-15 Curacyte Ag Hemmstoffe der urokinase, ihre herstellung und verwendung
DE10227666A1 (de) 2002-06-20 2004-01-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg (R)-2-(4-Amidinophenylaminomethyl)-1-methyl-5-[1-(carboxymethylamino)-1-(pyrrolidinocarbonyl)- ethyl]-benzimidazol, dessen Monohydrochlorid, Verfahren zu deren Herstellung sowie Verwendung als Arzneimittel
DE10227668A1 (de) 2002-06-20 2004-01-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Arzneimittel zur Behandlung des systemic inflammatory response syndrome
DE10301300B4 (de) 2003-01-15 2009-07-16 Curacyte Chemistry Gmbh Verwendung von acylierten 4-Amidino- und 4-Guanidinobenzylaminen zur Inhibierung von Plasmakallikrein
DE10322191B4 (de) 2003-05-16 2014-02-27 The Medicines Company (Leipzig) Gmbh N-sulfonylierte Aminosäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung
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EP2590945B1 (en) 2010-07-07 2014-04-30 The Medicines Company (Leipzig) GmbH Serine protease inhibitors

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US5955576A (en) * 1992-02-14 1999-09-21 Corvas International, Inc. Inhibitors of thrombosis
WO1994017817A1 (en) * 1993-02-12 1994-08-18 Corvas International, Inc. Inhibitors of thrombosis
CN1121068A (zh) * 1994-01-27 1996-04-24 三菱化学株式会社 脯氨酰胺衍生物
CN1147205A (zh) * 1994-03-04 1997-04-09 伊莱利利公司 抗血栓形成剂

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Design and Discovery of a Novel Dipeptidase IV (CD26)-Based Prodrug Approach;Carlos García-Aparicio et al.;《J. Med. Chem》;20060801;第49卷(第17期);第5340页右栏第35-37行及图1 *
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Synthesis, Conformation, and Interactions with Small Molecules of Bis(Cyclic Dipeptides);Hiroshi Tomiyasu et al.;《Helvetica Chimica Acta》;19820505;第65卷(第3期);第777页第1-2行及图1 *

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Publication number Publication date
CA2822350A1 (en) 2012-06-28
WO2012083436A1 (en) 2012-06-28
US8497245B2 (en) 2013-07-30
JP2014500280A (ja) 2014-01-09
CN103403018A (zh) 2013-11-20
US20120252743A1 (en) 2012-10-04
AU2011349022A1 (en) 2013-07-11
EP2655399A4 (en) 2014-07-30
EP2655399B1 (en) 2017-09-27
JP5923110B2 (ja) 2016-05-24
NO2655399T3 (enExample) 2018-02-24
ES2654440T3 (es) 2018-02-13
AU2011349022B2 (en) 2017-04-13
EP2655399A1 (en) 2013-10-30

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