tert-butyl (1R,2R,4R)-2-(((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)-4-((7-methoxy-2-(thiazol-2-yl)quinolin-4-yl)oxy)cyclopentane-1-carboxylate | 1073118-76-9

• 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: tert-butyl (1R,2R,4R)-2-(((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)-4-((7-methoxy-2-(thiazol-2-yl)quinolin-4-yl)oxy)cyclopentane-1-carboxylate
• CAS: 1073118-76-9
• 化学式: C₃₂H₃₇N₃O₇S
• 分子量: 607.728
• InChiKey: RUTZSQPAMGVYIN-BLOOORNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  43.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  125.94
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,2R,4R)-2-(((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)-4-((7-methoxy-2-(thiazol-2-yl)quinolin-4-yl)oxy)cyclopentane-1-carboxylate 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 2-(1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-(7-methoxy-2-thiazol-2-yl-quinolin-4-yloxy)-cyclopentanecarboxylic acid
  参考文献：
  名称：

  Structure–activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350

  摘要：

  SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl) sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (K-i = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.088
• 作为产物：
  描述：

  (1R,2R,4S)-2-((1R,2S)-1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-hydroxy-cyclopenteanecarboxylic acid tert-butyl ester 、 7-methoxy-2-(2-thiazolyl)-4-quinolinol 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以63%的产率得到tert-butyl (1R,2R,4R)-2-(((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropyl)carbamoyl)-4-((7-methoxy-2-(thiazol-2-yl)quinolin-4-yl)oxy)cyclopentane-1-carboxylate
  参考文献：
  名称：

  Structure–activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350

  摘要：

  SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.0(4,6)]octadec-7-ene-4-carbonyl](cyclopropyl) sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (K-i = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.088