| 1020745-65-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• CAS: 1020745-65-6
• 化学式: C₃₉H₅₆Cl₂N₆O₈
• 分子量: 807.815
• InChiKey: PCJILVWUBGPFAO-ZOPNRJJASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.19
• 重原子数：
  55.0
• 可旋转键数：
  14.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  186.48
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 tert-butyl N-[(1S)-1-cyclohexyl-2-[(1S,2S,5R)-6,6-dichloro-2-[[1-cyclobutyl-4-[[2-[[(1S)-2-(dimethylamino)-2-oxo-1-phenylethyl]amino]-2-oxoethyl]amino]-3,4-dioxobutan-2-yl]carbamoyl]-3-azabicyclo[3.1.0]hexan-3-yl]-2-oxoethyl]carbamate
  参考文献：
  名称：

  Potent and selective small molecule NS3 serine protease inhibitors of Hepatitis C virus with dichlorocyclopropylproline as P2 residue

  摘要：

  Starting from a pentapeptide Hepatitis C virus NS3 protease inhibitor, a number of alpha-ketoamide inhibitors based on novel dichlorocyclopropylproline P2 core were synthesized and investigated for their HCV NS3 serine protease activity. The key intermediate 3,4-dichlorocyclopropylproline was obtained through a dichloro carbene insertion to 3,4-dehydroproline. The size of the molecules was reduced significantly through a series of truncations of the initial pentapeptide. By varying P1 side chain in length and size, potency and selectivity were improved. A variety of aliphatic carbamate and urea capping groups were examined. In general, compounds with urea cappings were more potent and selective than their carbamate counterparts. The most potent compound was a tert-butyl urea analog. Variations at P3 position were also investigated. Among the three residues incorporated, tert-leucine was clearly superior, leading to compounds that had excellent enzyme potency and selectivity. The most potent compound achieved cell-based replicon assay EC50 of 40 nM. The most promising compound of all had excellent potency in both enzyme (K-i* = 9 nM) and replicon assays (EC50 = 100 nM). Its bioavailabilities were above 10% in all three animal species (rats, monkeys, and dogs). It has provided a lead for future investigations. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.002
• 作为产物：
  描述：

  3-Amino-4-cyclobutyl-N-{[((S)-dimethylcarbamoyl-phenyl-methyl)-carbamoyl]-methyl}-2-hydroxy-butyramide; hydrochloride 、 3-(2-tert-butoxycarbonylamino-2-cyclohexyl-acetyl)-6,6-dichloro-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid 在 N-甲基吗啉 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Potent and selective small molecule NS3 serine protease inhibitors of Hepatitis C virus with dichlorocyclopropylproline as P2 residue

  摘要：

  Starting from a pentapeptide Hepatitis C virus NS3 protease inhibitor, a number of alpha-ketoamide inhibitors based on novel dichlorocyclopropylproline P2 core were synthesized and investigated for their HCV NS3 serine protease activity. The key intermediate 3,4-dichlorocyclopropylproline was obtained through a dichloro carbene insertion to 3,4-dehydroproline. The size of the molecules was reduced significantly through a series of truncations of the initial pentapeptide. By varying P1 side chain in length and size, potency and selectivity were improved. A variety of aliphatic carbamate and urea capping groups were examined. In general, compounds with urea cappings were more potent and selective than their carbamate counterparts. The most potent compound was a tert-butyl urea analog. Variations at P3 position were also investigated. Among the three residues incorporated, tert-leucine was clearly superior, leading to compounds that had excellent enzyme potency and selectivity. The most potent compound achieved cell-based replicon assay EC50 of 40 nM. The most promising compound of all had excellent potency in both enzyme (K-i* = 9 nM) and replicon assays (EC50 = 100 nM). Its bioavailabilities were above 10% in all three animal species (rats, monkeys, and dogs). It has provided a lead for future investigations. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.002