(3S)-N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]morpholine-3-carboxamide trifluoroacetate salt | 1462904-32-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S)-N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]morpholine-3-carboxamide trifluoroacetate salt
• 英文别名: (3S)-N-[[2-(aminomethyl)-5-chlorophenyl]methyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]morpholine-3-carboxamide;2,2,2-trifluoroacetic acid
• CAS: 1462904-32-0
• 化学式: C₂HF₃O₂*C₁₉H₂₈ClN₃O₄
• 分子量: 511.926
• InChiKey: ORGCLDPWGSBROP-MOGJOVFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.68
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  142.19
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  (3S)-3,4-吗啉二羧酸 4-叔丁酯 在 哌啶 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 (3S)-N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]morpholine-3-carboxamide trifluoroacetate salt
  参考文献：
  名称：

  Heterocyclic core analogs of a direct thrombin inhibitor

  摘要：

  Thrombin is a serine protease that plays a key role in blood clotting. Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years ago. Seven analogs (2-8) of 1 in which the pyrrolidine core was replaced with various heterocycles were prepared and evaluated for activity against thrombin, clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog 6 was the most active, essentially matching the thrombin inhibitory activity of 1 with slightly improved selectivity over trypsin. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.002

文献信息

• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE THROMBINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2013148478A1

  公开（公告）日：2013-10-03

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: (I) or a pharmaceutically acceptable salt thereof, wherein Q is CH2, NR4, O, S, S(O) or S(O2), wherein R4 is H, C1-6 alkyl, aryl, or C3-8 cycloalkyl; R1 is a heterocycle or -(CR5R6)1-2NH2, wherein R5 and R6, each time in which they occur, are independently H, C1-6 alkyl, -CH2F,-CHF2, CF3 or -CH2OH; R2 is OH, NH2 or NHSO2CH3; and R3 is C1-6 alkyl.

  本发明的化合物具有以下结构，可用于抑制凝血酶和相关的血栓闭塞，其中Q为CH2、NR4、O、S、S（O）或S（O2），其中R4为H、C1-6烷基、芳基或C3-8环烷基；R1为杂环或-（CR5R6）1-2NH2，其中R5和R6，在它们每次出现时，独立地为H、C1-6烷基、-CH2F、-CHF2、CF3或-CH2OH；R2为OH、NH2或NHSO2CH3；R3为C1-6烷基，或其药学上可接受的盐。
• THROMBIN INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20150038498A1

  公开（公告）日：2015-02-05

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: (I) or a pharmaceutically acceptable salt thereof, wherein Q is CH 2 , NR 4 , O, S, S(O) or S(O 2 ), wherein R 4 is H, C 1-6 alkyl, aryl, or C 3-8 cycloalkyl; R 1 is a heterocycle or —(CR 5 R 6 )1-2NH2, wherein R 5 and R 6 , each time in which they occur, are independently H, C 1-6 alkyl, —CH 2 F, —CHF 2 , CF 3 or —CH 2 OH; R 2 is OH, NH 2 or NHSO 2 CH 3 ; and R 3 is C 1-6 alkyl.

  本发明的化合物具有以下结构（I）或其药学上可接受的盐，在抑制凝血酶和相关的血栓闭塞方面有用，其中Q为CH2，NR4，O，S，S（O）或S（O2），其中R4为H，C1-6烷基，芳基或C3-8环烷基；R1为杂环或-（CR5R6）1-2NH2，其中R5和R6在每次出现时独立地为H，C1-6烷基，-CH2F，-CHF2，CF3或-CH2OH；R2为OH，NH2或NHSO2CH3；R3为C1-6烷基。
• Thrombin inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US09133147B2

  公开（公告）日：2015-09-15

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein Q is CH2, NR4, O, S, S(O) or S(O2), wherein R4 is H, C1-6 alkyl, aryl, or C3-8 cycloalkyl; R1 is a heterocycle or —(CR5R6)1-2NH2, wherein R5 and R6, each time in which they occur, are independently H, C1-6 alkyl, —CH2F, —CHF2, CF3 or —CH2OH; R2 is OH, NH2 or NHSO2CH3; R3 is C1-6 alkyl.

  本发明的化合物在抑制凝血酶和相关血栓闭塞中有用，其结构如下：或其药学上可接受的盐，其中Q为CH2、NR4、O、S、S(O)或S(O2)，其中R4为H、C1-6烷基、芳香族或C3-8环烷基；R1为杂环或-(CR5R6)1-2NH2，其中R5和R6，在它们出现的每个时候，独立地为H、C1-6烷基、-CH2F、-CHF2、CF3或-CH2OH；R2为OH、NH2或NHSO2CH3；R3为C1-6烷基。
• US9133147B2
  申请人：——

  公开号：US9133147B2

  公开（公告）日：2015-09-15
• Heterocyclic core analogs of a direct thrombin inhibitor
  作者：Timothy A. Blizzard、Sanjay Singh、Basanagoud Patil、Naresh Chidurala、Venukrishnan Komanduri、Samarpita Debnath、Sergei Belyakov、Alejandro Crespo、Alice Struck、Marc Kurtz、Judyann Wiltsie、Xun Shen、Lisa Sonatore、Marta Arocho、Dale Lewis、Martin Ogletree、Tesfaye Biftu

  DOI：10.1016/j.bmcl.2014.01.002

  日期：2014.2

  Thrombin is a serine protease that plays a key role in blood clotting. Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years ago. Seven analogs (2-8) of 1 in which the pyrrolidine core was replaced with various heterocycles were prepared and evaluated for activity against thrombin, clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog 6 was the most active, essentially matching the thrombin inhibitory activity of 1 with slightly improved selectivity over trypsin. (C) 2014 Elsevier Ltd. All rights reserved.