N-(5-chloro-2-[1,2,4]triazol-1-yl-benzyl)-2-[3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(5-chloro-2-[1,2,4]triazol-1-yl-benzyl)-2-[3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]acetamide
• 英文别名: N-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-2-[3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-2-oxopyrazin-1-yl]acetamide
• 化学式: C₂₂H₁₉ClF₂N₈O₂
• 分子量: 500.895
• InChiKey: CRWXNHATECZVNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,5-二氯苯甲腈 在 镍 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 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 N-(5-chloro-2-[1,2,4]triazol-1-yl-benzyl)-2-[3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]acetamide
  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

• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE LA THROMBINE
  申请人：MERCK & CO INC

  公开号：WO2002064140A1

  公开（公告）日：2002-08-22

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein R2 is R3 is selected from the group consisting of 1) hydrogen, 2) halogen, 3) C 1-4 alkyl, 4) C 3-7 cycloalkyl, 5) CF3, 6) OCF3, 7) C 1-4 alkoxy, and 8) cyano; and R12 is a 5-membered heteroaryl ring having 2, 3, or 4 heteroatoms, provided that at least 1 heteroatom is N, and at most 1 of the heteroatoms is S, said ring being unsubstituted or substituted, at any one ring atom, with CH3.

  本发明的化合物在抑制凝血酶和相关的血栓闭塞方面有用，其结构如下：或其药学上可接受的盐，其中R2和R3选自以下组：1）氢，2）卤素，3）C 1-4 烷基，4）C 3-7 环烷基，5）CF3，6）O ，7）C 1-4 醇基，8）氰基；R12是一个具有2、3或4个杂原子的5元杂环芳基环，其中至少1个杂原子是N，至多1个杂原子是S，所述环未取代或在任何一个环原子上用CH3取代。
• Thrombin inhibitors
  申请人：——

  公开号：US20040097730A1

  公开（公告）日：2004-05-20

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein R2 is R3 is selected from the group consisting of 1) hydrogen, 2) halogen, 3) C 1-4 alkyl, 4) C 3-7 cycloalkyl, 5) CF3, 6) OCF3, 7) C 1-4 alkoxy, and 8) cyano; and R12 is a 5-membered heteroaryl ring having 2, 3, or 4 heteroatoms, provided that at least 1 heteroatom is N, and at most 1 of the heteroatoms is S, said ring being unsubstituted or substituted, at any one ring atom, with CH3. 1

  本发明的化合物具有以下结构，或其药学上可接受的盐，在抑制凝血酶和相关血栓闭塞方面有用，其中R2和R3从以下组中选择：1）氢，2）卤素，3）C 1-4 烷基，4）C 3-7 环烷基，5）CF3，6）O ，7）C 1-4 烷氧基和8）氰基；而R12是一个5元杂环芳基环，其中含有2、3或4个杂原子，至少1个杂原子是N，且最多1个杂原子是S，所述环在任何一个环原子上未取代或被取代，该取代基为CH3.
• THROMBIN INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1359913A1

  公开（公告）日：2003-11-12
• US7026324B2
  申请人：——

  公开号：US7026324B2

  公开（公告）日：2006-04-11