CN102464701B - 一类新型化合物、其制备方法及用途 - Google Patents

一类新型化合物、其制备方法及用途 Download PDF

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Publication number
CN102464701B
CN102464701B CN201010535094.4A CN201010535094A CN102464701B CN 102464701 B CN102464701 B CN 102464701B CN 201010535094 A CN201010535094 A CN 201010535094A CN 102464701 B CN102464701 B CN 102464701B
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China
Prior art keywords
prolyl
methyl
leucyl
acid
amide
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CN201010535094.4A
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English (en)
Chinese (zh)
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CN102464701A (zh
Inventor
单汉滨
黄雨
袁哲东
俞雄
李敏
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Livzon Pharmaceutical Group Inc
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Shanghai Institute of Pharmaceutical Industry
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.)
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Publication date
Priority to CN201010535094.4A priority Critical patent/CN102464701B/zh
Application filed by Shanghai Institute of Pharmaceutical Industry filed Critical Shanghai Institute of Pharmaceutical Industry
Priority to EP14183844.1A priority patent/EP2824097A1/en
Priority to EP11839747.0A priority patent/EP2639230A4/en
Priority to PCT/CN2011/081811 priority patent/WO2012062187A1/zh
Priority to JP2013538047A priority patent/JP6219720B2/ja
Priority to EP18208270.1A priority patent/EP3466961B1/en
Priority to US13/884,196 priority patent/US9434760B2/en
Publication of CN102464701A publication Critical patent/CN102464701A/zh
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    • 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
    • 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
    • C07K5/0215—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing natural amino acids, forming a peptide bond via their side chain functional group, e.g. epsilon-Lys, gamma-Glu
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • 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
    • 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
    • C07K5/06017—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
    • C07K5/06043—Leu-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
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
    • 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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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
CN201010535094.4A 2010-11-08 2010-11-08 一类新型化合物、其制备方法及用途 Active CN102464701B (zh)

Priority Applications (7)

Application Number Priority Date Filing Date Title
CN201010535094.4A CN102464701B (zh) 2010-11-08 2010-11-08 一类新型化合物、其制备方法及用途
EP11839747.0A EP2639230A4 (en) 2010-11-08 2011-11-04 PROLINAMID DERIVATIVE AS THROMBIN EMBROIDER, METHOD FOR THE PRODUCTION THEREOF AND THE APPLICATION THEREOF
PCT/CN2011/081811 WO2012062187A1 (zh) 2010-11-08 2011-11-04 作为凝血酶抑制剂的脯氨酰胺衍生物、其制备方法及应用
JP2013538047A JP6219720B2 (ja) 2010-11-08 2011-11-04 新規な化合物、その製造方法および用途
EP14183844.1A EP2824097A1 (en) 2010-11-08 2011-11-04 Prolinamide derivative as thrombin inhibitor, preparation method and application thereof
EP18208270.1A EP3466961B1 (en) 2010-11-08 2011-11-04 Prolinamide derivative as thrombin inhibitor
US13/884,196 US9434760B2 (en) 2010-11-08 2011-11-04 Prolinamide derivatives as thrombin inhibitors, preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201010535094.4A CN102464701B (zh) 2010-11-08 2010-11-08 一类新型化合物、其制备方法及用途

Publications (2)

Publication Number Publication Date
CN102464701A CN102464701A (zh) 2012-05-23
CN102464701B true CN102464701B (zh) 2015-10-21

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Application Number Title Priority Date Filing Date
CN201010535094.4A Active CN102464701B (zh) 2010-11-08 2010-11-08 一类新型化合物、其制备方法及用途

Country Status (5)

Country Link
US (1) US9434760B2 (https=)
EP (3) EP3466961B1 (https=)
JP (1) JP6219720B2 (https=)
CN (1) CN102464701B (https=)
WO (1) WO2012062187A1 (https=)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103833827B (zh) * 2012-11-27 2016-08-03 上海医药工业研究院 一种酰胺类化合物、其药物组合物、制备方法及应用
HUE061437T2 (hu) 2015-10-23 2023-06-28 Navitor Pharm Inc A Sestrin-GATOR2 kölcsönhatás modulátorai és ezek alkalmazásai
US10912750B2 (en) 2017-04-26 2021-02-09 Navitor Pharmaceuticals, Inc. Modulators of Sestrin-GATOR2 interaction and uses thereof
CN112041328B (zh) * 2018-04-26 2024-06-21 志瑞亚新药工业株式会社 二肽和含有该二肽的药物组合物
CN113164414A (zh) 2018-10-24 2021-07-23 纳维托制药有限公司 多晶型化合物和其用途
EP3873916B8 (en) * 2018-10-29 2025-03-26 Shanghai Synergy Pharmaceutical Sciences, Ltd. Novel dipeptide compounds and uses thereof
JP7693644B2 (ja) * 2019-07-08 2025-06-17 リゾルート，インコーポレイティド 血漿カリクレイン阻害薬の調製プロセス
TN2022000028A1 (en) 2019-08-06 2023-10-09 Biocryst Pharm Inc Process-scale synthesis of a plasma kallikrein inhibitor
CA3156436A1 (en) 2019-11-01 2021-05-06 Steven LEVENTER Methods of treatment using an mtorc1 modulator
WO2024169765A1 (zh) * 2023-02-16 2024-08-22 上海华汇拓医药科技有限公司 一种二肽类化合物的盐、其制备方法和用途

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1980002559A1 (fr) * 1979-05-11 1980-11-27 Pentapharm Ag Derives tripeptidiques
WO2002060894A2 (en) * 2001-01-30 2002-08-08 Bristol-Myers Squibb Company Sulfonamide lactam inhibitors of factor xa
CN101605540A (zh) * 2006-12-14 2009-12-16 埃克塞利希斯股份有限公司 使用mek抑制剂的方法

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US4101653A (en) 1974-11-08 1978-07-18 Mitsubishi Chemical Industries Limited N2 -arylsulfonyl-argininamides and the pharmaceutically acceptable salts thereof
HU178398B (en) 1979-06-12 1982-04-28 Gyogyszerkutato Intezet Process for producing new agmatine derivatives of activity against haemagglutination
SE9103612D0 (sv) 1991-12-04 1991-12-04 Astra Ab New peptide derivatives
US5583146A (en) * 1992-12-02 1996-12-10 Bristol-Myers Squibb Company Heterocyclic thrombin inhibitors
SE9301916D0 (sv) * 1993-06-03 1993-06-03 Ab Astra New peptides derivatives
AU1025795A (en) 1994-01-27 1995-08-03 Mitsubishi Chemical Corporation Prolineamide derivatives
JP3840668B2 (ja) * 1994-01-27 2006-11-01 三菱化学株式会社 プロリンアミド誘導体
ZA951617B (en) 1994-03-04 1997-02-27 Lilly Co Eli Antithrombotic agents.
US5510369A (en) 1994-07-22 1996-04-23 Merck & Co., Inc. Pyrrolidine thrombin inhibitors
CZ245797A3 (cs) * 1995-02-17 1998-06-17 Basf Aktiengesellschaft Derivát amidinu dipeptidu jako inhibitor thrombinu
AU709088B2 (en) 1995-10-24 1999-08-19 Merck & Co., Inc. Thrombin inhibitors
FI105274B (fi) 1996-03-15 2000-07-14 Upm Kymmene Oy Menetelmä ei-hormonivaikutteisten, tyydyttymättömien kasvisteroidien hydraamiseksi ja käytetyn katalyytin regenerointi
EP1051431A1 (de) * 1998-01-26 2000-11-15 Basf Aktiengesellschaft Thrombininhibitoren
CZ20013577A3 (cs) * 1999-04-09 2002-07-17 Basf Aktiengesellschaft Inhibitory komplementních proteáz s nízkou molekulovou hmotností
DE10064797A1 (de) * 2000-12-22 2002-06-27 Knoll Ag Orale und parenterale pharmazeutische Formulierung, umfassend eine niedermolekulare Thrombininhibitor-Pro-Pharmakon

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1980002559A1 (fr) * 1979-05-11 1980-11-27 Pentapharm Ag Derives tripeptidiques
WO2002060894A2 (en) * 2001-01-30 2002-08-08 Bristol-Myers Squibb Company Sulfonamide lactam inhibitors of factor xa
CN101605540A (zh) * 2006-12-14 2009-12-16 埃克塞利希斯股份有限公司 使用mek抑制剂的方法

Also Published As

Publication number Publication date
EP3466961A1 (en) 2019-04-10
EP3466961B1 (en) 2022-04-06
EP2639230A4 (en) 2014-03-12
US20130296245A1 (en) 2013-11-07
US9434760B2 (en) 2016-09-06
JP6219720B2 (ja) 2017-10-25
EP2824097A1 (en) 2015-01-14
EP2639230A1 (en) 2013-09-18
JP2013543850A (ja) 2013-12-09
CN102464701A (zh) 2012-05-23
WO2012062187A1 (zh) 2012-05-18

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