1-(2(R)-amino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid 5-chloro-2-[1,2,4]triazol-1-yl-benzylamide

• 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: 1-(2(R)-amino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid 5-chloro-2-[1,2,4]triazol-1-yl-benzylamide
• 英文别名: (2S)-1-[(2R)-2-amino-3-pyridin-2-ylpropanoyl]-N-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]pyrrolidine-2-carboxamide
• 化学式: C₂₂H₂₄ClN₇O₂
• 分子量: 453.931
• InChiKey: MORMTJZNCIRFQZ-QUCCMNQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,5-二氯苯甲腈 在 镍 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 乙醇 、 氨 、 氢气 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 1-(2(R)-amino-3-pyridin-2-yl-propionyl)pyrrolidine-2(S)-carboxylic acid 5-chloro-2-[1,2,4]triazol-1-yl-benzylamide
  参考文献：
  名称：

  Discovery and Evaluation of Potent P₁ Aryl Heterocycle-Based Thrombin Inhibitors

  摘要：

  In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P-1 region. Various benzylamines were coupled to a pyridine/pyrazinone P-2-P-3 template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K-i of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P-1 aryl heterocycles with a variety of P-2-P-3 groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P-1 will allow for more diversification in the P-2-P-3 region to ultimately address additional pharmacological concerns.

  DOI：

  10.1021/jm030303e

文献信息

• Discovery and Evaluation of Potent P₁ Aryl Heterocycle-Based Thrombin Inhibitors
  作者：Mary Beth Young、James C. Barrow、Kristen L. Glass、George F. Lundell、Christina L. Newton、Janetta M. Pellicore、Kenneth E. Rittle、Harold G. Selnick、Kenneth J. Stauffer、Joseph P. Vacca、Peter D. Williams、Dennis Bohn、Franklin C. Clayton、Jacquelynn J. Cook、Julie A. Krueger、Lawrence C. Kuo、S. Dale Lewis、Bobby J. Lucas、Daniel R. McMasters、Cynthia Miller-Stein、Beth L. Pietrak、Audrey A. Wallace、Rebecca B. White、Bradley Wong、Youwei Yan、Philippe G. Nantermet

  DOI：10.1021/jm030303e

  日期：2004.6.1

  In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P-1 region. Various benzylamines were coupled to a pyridine/pyrazinone P-2-P-3 template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K-i of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P-1 aryl heterocycles with a variety of P-2-P-3 groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P-1 will allow for more diversification in the P-2-P-3 region to ultimately address additional pharmacological concerns.