{1-(R)-benzyl-2-oxo-2-[2-(2-[1,2,4]triazol-1-yl-benzyl-carbamoyl)pyrrolidin-1-(S)-yl]-ethyl}carbamic acid tert-butyl ester | 724710-05-8

• 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-(R)-benzyl-2-oxo-2-[2-(2-[1,2,4]triazol-1-yl-benzyl-carbamoyl)pyrrolidin-1-(S)-yl]-ethyl}carbamic acid tert-butyl ester
• CAS: 724710-05-8
• 化学式: C₂₈H₃₄N₆O₄
• 分子量: 518.616
• InChiKey: SVRMBFVPTIDVNG-VWNXMTODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  38.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  118.45
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  {1-(R)-benzyl-2-oxo-2-[2-(2-[1,2,4]triazol-1-yl-benzyl-carbamoyl)pyrrolidin-1-(S)-yl]-ethyl}carbamic acid tert-butyl ester 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以42 mg的产率得到(2S)-1-[(2R)-2-amino-3-phenylpropanoyl]-N-[[2-(1,2,4-triazol-1-yl)phenyl]methyl]pyrrolidine-2-carboxamide
  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-(1,2,4-三唑-1-基)苯甲腈 在 palladium on activated charcoal N-羟基-7-氮杂苯并三氮唑 、 氢气 、 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 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、379.21 kPa 条件下， 生成 {1-(R)-benzyl-2-oxo-2-[2-(2-[1,2,4]triazol-1-yl-benzyl-carbamoyl)pyrrolidin-1-(S)-yl]-ethyl}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