(S)-tert-butyl (2-phenyl-1-(3-phenyl-1H-1,2,4-triazol-5-yl)ethyl)carbamate | 872017-66-8

• 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)-tert-butyl (2-phenyl-1-(3-phenyl-1H-1,2,4-triazol-5-yl)ethyl)carbamate
• 英文别名: (S)-tert-butyl 2-phenyl-1-(5-phenyl-2H-1,2,4-triazol-3-yl)ethylcarbamate；tert-butyl N-[(1S)-2-phenyl-1-(3-phenyl-1H-1,2,4-triazol-5-yl)ethyl]carbamate
• CAS: 872017-66-8
• 化学式: C₂₁H₂₄N₄O₂
• 分子量: 364.447
• InChiKey: FIYABRHDDHWDDY-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl (2-phenyl-1-(3-phenyl-1H-1,2,4-triazol-5-yl)ethyl)carbamate 在 吡啶 、 双(2-氧代-3-恶唑烷基)次磷酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 31.0h， 生成 trans-4-(aminomethyl)-N-((S)-2-phenyl-1-(3-phenyl-1H-1,2,4-triazol-5-yl)ethyl)cyclohexanecarboxamide bis(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：

  BOC-L-苯丙氨酸 在 吡啶 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 、 肼 作用下， 以 乙腈 为溶剂， 反应 40.0h， 生成 (S)-tert-butyl (2-phenyl-1-(3-phenyl-1H-1,2,4-triazol-5-yl)ethyl)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
• Phenylimidazoles as Potent and Selective Inhibitors of Coagulation Factor XIa with in Vivo Antithrombotic Activity
  作者：Jon J. Hangeland、Todd J. Friends、Karen A. Rossi、Joanne M. Smallheer、Cailan Wang、Zhong Sun、James R. Corte、Tianan Fang、Pancras C. Wong、Alan R. Rendina、Frank A. Barbera、Jeffrey M. Bozarth、Joseph M. Luettgen、Carol A. Watson、Ge Zhang、Anzhi Wei、Vidhyashankar Ramamurthy、Paul E. Morin、Gregory S. Bisacchi、Srinath Subramaniam、Piramanayagam Arunachalam、Arvind Mathur、Dietmar A. Seiffert、Ruth R. Wexler、Mimi L. Quan

  DOI：10.1021/jm5010607

  日期：2014.12.11

  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.