2-phenyl-4-(1-(S)-benzyloxycarbonylamino-2-phenylethyl)-1H-imidazole | 269085-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-phenyl-4-(1-(S)-benzyloxycarbonylamino-2-phenylethyl)-1H-imidazole
• 英文别名: (S)-benzyl (2-phenyl-1-(2-phenyl-1H-imidazol-4-yl)ethyl)carbamate；benzyl N-[(1S)-2-phenyl-1-(2-phenyl-1H-imidazol-4-yl)ethyl]carbamate；benzyl N-[(1S)-2-phenyl-1-(2-phenyl-1H-imidazol-5-yl)ethyl]carbamate
• CAS: 269085-42-9
• 化学式: C₂₅H₂₃N₃O₂
• 分子量: 397.477
• InChiKey: XAEGOMIUIMZOLZ-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 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：
  67
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-phenyl-4-(1-(S)-benzyloxycarbonylamino-2-phenylethyl)-1H-imidazole 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 2-phenyl-4-(1-(S)-amino-2-phenylethyl)-1H-imidazole
  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：

  苯甲脒 在 sodium formate 、 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 38.0h， 以8%的产率得到2-phenyl-4-(1-(S)-benzyloxycarbonylamino-2-phenylethyl)-1H-imidazole
  参考文献：
  名称：

  [EN] FIVE-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS
  [FR] HETEROCYCLES A CINQ CHAINONS UTILISES COMME INHIBITEURS DE LA SERINE PROTEASE

  摘要：

  公开号：

  WO2005123050A3

文献信息

• Synthesis of amino acid-derived imidazoles from enantiopure N-protected α-amino glyoxals
  作者：Michelle Groarke、M.Anthony McKervey、Mark Nieuwenhuyzen

  DOI：10.1016/s0040-4039(99)02267-4

  日期：2000.2

  A range of novel imidazoles, including three histidine derivatives, with chiral side chains derived from amino acids and dipeptides have been synthesised from N-Cbz-protected alpha-amino glyoxals. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Chiral imidazole derivatives synthesis from enantiopure N-protected α-amino acids
  作者：Filip Bureš、Jiří Kulhánek

  DOI：10.1016/j.tetasy.2005.01.049

  日期：2005.4

  A route to the preparation of enantiopure ligands based on a 2-phenylimidazol ring is described. The stereogenic centre is placed into the chain bonded to the fourth carbon of the imidazole ring. The synthesis starts from inexpensive and readily available N-protected alpha-amino acids, as the source of chirality, which are converted into appropriate alpha-diazoketones and, consequently, into alpha-bromoketones. These alpha-bromoketones are good precursors for reactions with amidines to provide the imidazole ring. The deprotection into the final products was carried out using hydrogen. (c) 2005 Elsevier Ltd. All rights reserved.
• [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.