CN104039788A - 吡唑并[3,4-c]吡啶类衍生物、其制备方法及其在医药上的应用 - Google Patents

吡唑并[3,4-c]吡啶类衍生物、其制备方法及其在医药上的应用 Download PDF

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CN104039788A
CN104039788A CN201380004979.3A CN201380004979A CN104039788A CN 104039788 A CN104039788 A CN 104039788A CN 201380004979 A CN201380004979 A CN 201380004979A CN 104039788 A CN104039788 A CN 104039788A
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carbonyls
phenyl
mmol
pyrazolos
morpholine
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CN104039788B (zh
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许建烟
吕贺军
屈博磊
董庆
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Jiangsu Hengrui Medicine Co Ltd
Shanghai Hengrui Pharmaceutical Co Ltd
Shanghai Shengdi Pharmaceutical Co Ltd
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Jiangsu Hengrui Medicine Co Ltd
Shanghai Hengrui Pharmaceutical Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
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    • 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
    • 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
    • C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—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 one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
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    • C07D211/76—Oxygen atoms attached in position 2 or 6
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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    • C07—ORGANIC CHEMISTRY
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    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

一种吡唑[3,4-c]吡啶类衍生物、其制备方法及含有该衍生物的药物组合物及其作为治疗剂，特别是作为Xa因子抑制剂在制备治疗血栓栓塞等疾病的药物中的用途。

Description

PCT国内申请，说明书已公开。

Claims (1)

  1. PCT国内申请，权利要求书已公开。
CN201380004979.3A 2012-09-18 2013-08-29 吡唑并[3,4-c]吡啶类衍生物、其制备方法及其在医药上的应用 Expired - Fee Related CN104039788B (zh)

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Application Number Priority Date Filing Date Title
CN201380004979.3A CN104039788B (zh) 2012-09-18 2013-08-29 吡唑并[3,4-c]吡啶类衍生物、其制备方法及其在医药上的应用

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN201210349492 2012-09-18
CN201210349492.6 2012-09-18
CN2012103494926 2012-09-18
PCT/CN2013/082535 WO2014044113A1 (zh) 2012-09-18 2013-08-29 吡唑并[3,4-c]吡啶类衍生物、其制备方法及其在医药上的应用
CN201380004979.3A CN104039788B (zh) 2012-09-18 2013-08-29 吡唑并[3,4-c]吡啶类衍生物、其制备方法及其在医药上的应用

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109956886A (zh) * 2017-12-14 2019-07-02 连云港恒运药业有限公司 (z)-[(4-甲氧基苯基)亚肼基]氯乙酸乙酯的制备方法
CN113214142A (zh) * 2020-01-21 2021-08-06 浙江九洲药业股份有限公司 一种阿哌沙班的中间体及制备方法

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WO2015162551A1 (en) * 2014-04-21 2015-10-29 Mylan Laboratories Ltd Process for the preparation of apixaban
WO2016005560A1 (en) * 2014-07-11 2016-01-14 Laboratorios Lesvi, S.L. Process for prepararing apixaban
CN104311574B (zh) * 2014-09-19 2016-04-20 广东东阳光药业有限公司 含有噻唑的吡唑并哌啶酮类化合物及其组合物及用途
CN104311558B (zh) * 2014-09-19 2016-06-01 广东东阳光药业有限公司 含有环己烷取代基的吡唑并哌啶酮类化合物及其组合物及用途
CN104311555B (zh) * 2014-09-19 2016-04-20 广东东阳光药业有限公司 吡唑并哌啶酮类化合物及其组合物及用途
CN104277041B (zh) * 2014-09-19 2016-01-06 广东东阳光药业有限公司 含取代甲基的芳香环取代基的吡唑并哌啶酮类化合物及其组合物及用途
CN104277040B (zh) * 2014-09-19 2016-04-20 广东东阳光药业有限公司 含有酰基哌嗪酮取代基的吡唑并哌啶酮类化合物及其组合物及用途
CN104327074B (zh) * 2014-09-19 2016-01-06 广东东阳光药业有限公司 含有内酰胺取代基的吡唑并哌啶酮类化合物及其组合物及用途
CN104311575B (zh) * 2014-09-19 2016-04-20 广东东阳光药业有限公司 含有稠环的吡唑并哌啶酮类化合物及其组合物及用途
WO2016067308A1 (en) * 2014-10-28 2016-05-06 Jubilant Generics Limited (Formerly Jubilant Life Sciences Division) Process for the preparation of apixaban and intermediates thereof
CN104513239B (zh) * 2014-12-10 2017-08-22 沈阳药科大学 吡唑并[3,4‑c]吡啶‑7‑酮类化合物及其应用
CN105254630A (zh) * 2015-11-16 2016-01-20 江苏康缘药业股份有限公司 一种阿哌沙班的制备方法
WO2024084217A1 (en) * 2022-10-19 2024-04-25 Kalvista Pharmaceuticals Limited 3a,4,5,6-tetrahydro-1 h-pyrazolo[3,4-c]pyridin-7(7ah)-one derivatives as factor xiia inhibitors
CN116375703A (zh) * 2023-03-29 2023-07-04 常州制药厂有限公司 一种阿哌沙班的合成工艺

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CN1578660A (zh) * 2001-09-21 2005-02-09 百时美施贵宝公司 含有内酰胺的化合物及其衍生物作为Xa因子的抑制剂
CN101340933A (zh) * 2005-08-17 2009-01-07 百时美施贵宝公司 具有环糊精的因子xa抑制剂包合配合物
CN103242310A (zh) * 2012-02-10 2013-08-14 苏州迈泰生物技术有限公司 吡唑并吡啶酮类化合物及其在制备抗凝血药物中的用途

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TWI320039B (en) * 2001-09-21 2010-02-01 Lactam-containing compounds and derivatives thereof as factor xa inhibitors
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CN1578660A (zh) * 2001-09-21 2005-02-09 百时美施贵宝公司 含有内酰胺的化合物及其衍生物作为Xa因子的抑制剂
CN101340933A (zh) * 2005-08-17 2009-01-07 百时美施贵宝公司 具有环糊精的因子xa抑制剂包合配合物
CN103242310A (zh) * 2012-02-10 2013-08-14 苏州迈泰生物技术有限公司 吡唑并吡啶酮类化合物及其在制备抗凝血药物中的用途

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109956886A (zh) * 2017-12-14 2019-07-02 连云港恒运药业有限公司 (z)-[(4-甲氧基苯基)亚肼基]氯乙酸乙酯的制备方法
CN109956886B (zh) * 2017-12-14 2023-03-07 连云港恒运药业有限公司 (z)-[(4-甲氧基苯基)亚肼基]氯乙酸乙酯的制备方法
CN113214142A (zh) * 2020-01-21 2021-08-06 浙江九洲药业股份有限公司 一种阿哌沙班的中间体及制备方法
CN113214142B (zh) * 2020-01-21 2024-01-30 浙江九洲药业股份有限公司 一种阿哌沙班的中间体及制备方法

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