(S)-benzyl (1-(5-oxo-1-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)-2-phenylethyl)carbamate | 872017-69-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-benzyl (1-(5-oxo-1-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)-2-phenylethyl)carbamate
• 英文别名: (S)-benzyl 1-(5-oxo-1-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)-2-phenylethylcarbamate；benzyl N-[(1S)-1-(5-oxo-1-phenyl-4H-1,2,4-triazol-3-yl)-2-phenylethyl]carbamate
• CAS: 872017-69-1
• 化学式: C₂₄H₂₂N₄O₃
• 分子量: 414.464
• InChiKey: OOPDAUMWTXLTKI-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  83
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-benzyl (1-(5-oxo-1-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)-2-phenylethyl)carbamate 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 19.0h， 生成 trans-4-(aminomethyl)-N-((S)-1-(5-oxo-1-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)-2-phenylethyl)cyclohexanecarboxamide trifluoroacetic acid salt
  参考文献：
  名称：

  Phenylimidazoles as Potent and Selective Inhibitors of Coagulation Factor XIa with in Vivo Antithrombotic Activity

  摘要：

  Novel inhibitors of FXIa containing an (S)-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine core have been optimized to provide compound 16b, a potent, reversible inhibitor of FXIa (K-i = 0.3 nM) having in vivo antithrombotic efficacy in the rabbit AV-shunt thrombosis model (ID50 = 0.6 mg/kg + 1 mg kg(-1) h(-1)). Initial analog selection was informed by molecular modeling using compounds 11a and 11h overlaid onto the X-ray crystal structure of tetrahydroquinoline 3 complexed to FXIa. Further optimization was achieved by specific modifications derived from careful analysis of the X-ray crystal structure of the FXIa/11h complex. Compound 16b was well tolerated and enabled extensive pharmacologic evaluation of the FXIa mechanism up to the ID90 for thrombus inhibition.

  DOI：

  10.1021/jm5010607
• 作为产物：
  描述：

  N-苄氧羰基-L-苯丙氨腈 在 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 69.0h， 生成 (S)-benzyl (1-(5-oxo-1-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)-2-phenylethyl)carbamate
  参考文献：
  名称：

  Phenylimidazoles as Potent and Selective Inhibitors of Coagulation Factor XIa with in Vivo Antithrombotic Activity

  摘要：

  Novel inhibitors of FXIa containing an (S)-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine core have been optimized to provide compound 16b, a potent, reversible inhibitor of FXIa (K-i = 0.3 nM) having in vivo antithrombotic efficacy in the rabbit AV-shunt thrombosis model (ID50 = 0.6 mg/kg + 1 mg kg(-1) h(-1)). Initial analog selection was informed by molecular modeling using compounds 11a and 11h overlaid onto the X-ray crystal structure of tetrahydroquinoline 3 complexed to FXIa. Further optimization was achieved by specific modifications derived from careful analysis of the X-ray crystal structure of the FXIa/11h complex. Compound 16b was well tolerated and enabled extensive pharmacologic evaluation of the FXIa mechanism up to the ID90 for thrombus inhibition.

  DOI：

  10.1021/jm5010607

文献信息

• [EN] FIVE-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS<br/>[FR] HETEROCYCLES A CINQ CHAINONS UTILISES COMME INHIBITEURS DE LA SERINE PROTEASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2005123050A3

  公开（公告）日：2007-01-04