(3R,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-[4-(2-oxo-2H-pyridin-1-yl)-benzoylamino]-pyrrolidine-1-carboxylic acid ethyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-[4-(2-oxo-2H-pyridin-1-yl)-benzoylamino]-pyrrolidine-1-carboxylic acid ethyl ester
• 英文别名: (3R,4S)-ethyl 3-(2-chlorothiophene-5-carboxamido)-4-(4-(2-oxopyridin-1(2H)-yl)benzamido)pyrrolidine-1-carboxylate；ethyl (3R,4S)-3-[(5-chlorothiophene-2-carbonyl)amino]-4-[[4-(2-oxopyridin-1-yl)benzoyl]amino]pyrrolidine-1-carboxylate
• 化学式: C₂₄H₂₃ClN₄O₅S
• 分子量: 514.989
• InChiKey: VCOPBIUVMSEQNG-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氯噻吩-5-甲酸 在 哌啶 、 N-甲基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (3R,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-[4-(2-oxo-2H-pyridin-1-yl)-benzoylamino]-pyrrolidine-1-carboxylic acid ethyl ester
  参考文献：
  名称：

  Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications

  摘要：

  We previously reported a series of enantiopure cis-(1 R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa K; of 0.50 nM, PT EC2x of 2.1 mu M in human plasma, bioavailability of 25% and t z of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.020

文献信息

• Lactam-containing cyclic diamines and derivatives as factor Xa inhibitors
  申请人：——

  公开号：US20040204454A1

  公开（公告）日：2004-10-14

  The present application describes lactam-containing cyclic diamines and derivatives thereof of Formula I: P 4 -M-M 4 I or pharmaceutically acceptable salt forms thereof, wherein M is a non-aromatic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  本申请描述了公式I：P4-M-M4I或其药学上可接受的盐形式的含有内酰胺的环状二胺及其衍生物，其中M是非芳香性碳环或杂环。本发明化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是因子Xa的抑制剂。
• LACTAM CONTAINING CYCLIC DIAMINES AND DERIVATIVES AS FACTOR XA INHIBITORS
  申请人：Qiao X Jennifer

  公开号：US20070135428A1

  公开（公告）日：2007-06-14

  The present application describes lactam-containing cyclic diamines and derivatives thereof of Formula I: P 4 -M-M 4 I or pharmaceutically acceptable salt forms thereof, wherein M is a non-aromatic carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  本申请描述了公式I：P4-M-M4I或其药学上可接受的盐形式的含有内酰胺的环状二胺及其衍生物，其中M为非芳香族碳环或杂环。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是Xa因子的抑制剂。
• US7205318B2
  申请人：——

  公开号：US7205318B2

  公开（公告）日：2007-04-17