(3-[1,2,4]Triazol-1-yl-pyridin-2-ylmethyl)-carbamic acid tert-butyl ester | 449758-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (3-[1,2,4]Triazol-1-yl-pyridin-2-ylmethyl)-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[[3-(1,2,4-triazol-1-yl)pyridin-2-yl]methyl]carbamate
• CAS: 449758-30-9
• 化学式: C₁₃H₁₇N₅O₂
• 分子量: 275.31
• InChiKey: WINXLNZSABIGDD-UHFFFAOYSA-N

物化性质

• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-[1,2,4]Triazol-1-yl-pyridin-2-ylmethyl)-carbamic acid tert-butyl ester 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 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 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 2-[6-Chloro-3-(2,2-difluoro-2-pyridin-2-yl-ethylamino)-2-oxo-2H-pyrazin-1-yl]-N-(3-[1,2,4]triazol-1-yl-pyridin-2-ylmethyl)-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
• 作为产物：
  描述：

  2-氰基-3-氟吡啶 在 镍 甲醇 、 氨 、 氢气 、 caesium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 生成 (3-[1,2,4]Triazol-1-yl-pyridin-2-ylmethyl)-carbamic acid tert-butyl ester
  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

• Thrombin inhibitors
  申请人：——

  公开号：US20030158218A1

  公开（公告）日：2003-08-21

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1 wherein R 1 is, for example, hydrogen, Cl, or cyano, and R 2 is, for example, hydrogen, 2

  本发明的化合物在抑制凝血酶及相关血栓闭塞方面具有以下结构的有用： 1 其中R 1 例如是氢、氯或氰基，而R 2 例如是氢、 2
• [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：Merck & Co., Inc.

  公开号：EP1359913A1

  公开（公告）日：2003-11-12
• US6610701B2
  申请人：——

  公开号：US6610701B2

  公开（公告）日：2003-08-26
• US7026324B2
  申请人：——

  公开号：US7026324B2

  公开（公告）日：2006-04-11