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CN115667268A - 一种glp-1受体激动剂游离碱的制备方法 - Google Patents

一种glp-1受体激动剂游离碱的制备方法 Download PDF

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Publication number
CN115667268A
CN115667268A CN202180038229.2A CN202180038229A CN115667268A CN 115667268 A CN115667268 A CN 115667268A CN 202180038229 A CN202180038229 A CN 202180038229A CN 115667268 A CN115667268 A CN 115667268A
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Prior art keywords
acid
compound
formula
phenyl
reaction
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CN115667268B (zh
Inventor
胡海文
傅鸿樑
陈芬芬
周鑫洁
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Hangzhou Zhongmei Huadong Pharmaceutical Co Ltd
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Hangzhou Zhongmei Huadong Pharmaceutical Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

本发明提供了一种GLP‑1受体激动剂游离碱的制备方法，更具体而言，提供了(S)‑2‑(3S,8S)‑3‑(4‑(3,4‑二氯苄氧基)苯基‑7‑((S)‑1‑苯丙基)‑2,3,6,7,8,9‑六氢‑[1,4]‑二氧杂环己烯并[2,3‑g]异喹啉‑8‑甲酰氨基)‑3‑(4‑(2,3‑二甲基吡啶‑4‑基)苯基)丙酸的制备方法。首先，通过将化合物III与缩合剂反应形成活性酯，使氨基有机酸盐在原位游离，直接参与酰胺缩合反应。接着，在水解反应中，通过酸碱中和的后处理方式，使(S)‑2‑(3S,8S)‑3‑(4‑(3,4‑二氯苄氧基)苯基‑7‑((S)‑1‑苯丙基)‑2,3,6,7,8,9‑六氢‑[1,4]‑二氧杂环己烯并[2,3‑g]异喹啉‑8‑甲酰氨基)‑3‑(4‑(2,3‑二甲基吡啶‑4‑基)苯基)丙酸以较高的纯度在合适的溶剂中析出。该方法两步反应收率最高可达80％以上，纯度达到98％以上，并能够实现大规模制备，可以应用于工业化生产。

Description

PCT国内申请，说明书已公开。

Claims (11)

  1. PCT国内申请，权利要求书已公开。
CN202180038229.2A 2020-05-28 2021-05-26 一种glp-1受体激动剂游离碱的制备方法 Active CN115667268B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN2020104658025 2020-05-28
CN202010465802 2020-05-28
PCT/CN2021/095969 WO2021238964A1 (zh) 2020-05-28 2021-05-26 一种glp-1受体激动剂游离碱的制备方法

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CN115667268A true CN115667268A (zh) 2023-01-31
CN115667268B CN115667268B (zh) 2024-09-24

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US (1) US20230348484A1 (zh)
EP (1) EP4159737A4 (zh)
CN (1) CN115667268B (zh)
TW (1) TW202210487A (zh)
WO (1) WO2021238964A1 (zh)

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Publication number Priority date Publication date Assignee Title
WO2025057134A2 (en) 2023-09-14 2025-03-20 Ascletis Pharma (China) Co., Limited Glp-1r agonist and therapeutic method thereof

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006012256A2 (en) * 2004-06-29 2006-02-02 Aventis Pharmaceuticals Inc. Fkbp binding composition and pharmaceutical use thereof
CN101959405A (zh) * 2008-03-07 2011-01-26 转化技术制药公司 治疗糖尿病的氧杂二氮杂蒽化合物
CN102378574A (zh) * 2009-03-30 2012-03-14 转化技术制药公司 取代的偶氮蒽衍生物、药物组合物及其使用方法
WO2015048819A1 (en) * 2013-09-30 2015-04-02 The Regents Of The University Of California Anti-alphavbeta1 integrin compounds and methods
WO2019103060A1 (ja) * 2017-11-22 2019-05-31 第一三共株式会社 縮合三環化合物
CN109824755A (zh) * 2019-04-09 2019-05-31 湖南华腾制药有限公司 N-叔丁氧羰基-l-亮氨酰-l-苯丙氨酸甲酯的生产方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006012256A2 (en) * 2004-06-29 2006-02-02 Aventis Pharmaceuticals Inc. Fkbp binding composition and pharmaceutical use thereof
CN101959405A (zh) * 2008-03-07 2011-01-26 转化技术制药公司 治疗糖尿病的氧杂二氮杂蒽化合物
CN102378574A (zh) * 2009-03-30 2012-03-14 转化技术制药公司 取代的偶氮蒽衍生物、药物组合物及其使用方法
WO2015048819A1 (en) * 2013-09-30 2015-04-02 The Regents Of The University Of California Anti-alphavbeta1 integrin compounds and methods
WO2019103060A1 (ja) * 2017-11-22 2019-05-31 第一三共株式会社 縮合三環化合物
CN109824755A (zh) * 2019-04-09 2019-05-31 湖南华腾制药有限公司 N-叔丁氧羰基-l-亮氨酰-l-苯丙氨酸甲酯的生产方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BERTRAND LE BOURDONNEC等: "Synthesis and Pharmacological Evaluation of Novel Octahydro-1H-pyrido[1, 2-a]pyrazine as í-Opioid Receptor Antagonists", 《J. MED. CHEM.》, vol. 49, no. 25, XP055719691, DOI: 10.1021/jm0604878 *

Also Published As

Publication number Publication date
CN115667268B (zh) 2024-09-24
EP4159737A1 (en) 2023-04-05
EP4159737A4 (en) 2024-10-09
US20230348484A1 (en) 2023-11-02
WO2021238964A1 (zh) 2021-12-02
TW202210487A (zh) 2022-03-16

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