(1R,12E,22S,25S)-N-((1R,2S)-1-{[(cyclopropylsukfonyl)amino]carbonyl}-2-ethenylcyclopropyl)-22-(1-methylethyl)-3,23-dioxo-2-oxa-19-thia-4,21,24,28-tetraazapentacyclo[22.2.1.1(4,7).1(17,20).0(6,11)]octacosa-6,8,10,12,17,20(28)-hexaene-25-carboxamide | 957474-85-0

• 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: (1R,12E,22S,25S)-N-((1R,2S)-1-{[(cyclopropylsukfonyl)amino]carbonyl}-2-ethenylcyclopropyl)-22-(1-methylethyl)-3,23-dioxo-2-oxa-19-thia-4,21,24,28-tetraazapentacyclo[22.2.1.1(4,7).1(17,20).0(6,11)]octacosa-6,8,10,12,17,20(28)-hexaene-25-carboxamide
• 英文别名: (1R,12E,22S,25S)-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-3,23-dioxo-22-propan-2-yl-2-oxa-19-thia-4,21,24,28-tetrazapentacyclo[22.2.1.14,7.117,20.06,11]nonacosa-6,8,10,12,17,20(28)-hexaene-25-carboxamide
• CAS: 957474-85-0
• 化学式: C₃₆H₄₄N₆O₇S₂
• 分子量: 736.913
• InChiKey: MDTOFXVUZWSWEZ-GWVCBXLGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  51
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  200
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide 、 (1R,12E,22S,25S)-3,23-dioxo-22-propan-2-yl-2-oxa-19-thia-4,21,24,28-tetrazapentacyclo[22.2.1.14,7.117,20.06,11]nonacosa-6,8,10,12,17,20(28)-hexaene-25-carboxylic acid 在 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以36 mg的产率得到(1R,12E,22S,25S)-N-((1R,2S)-1-{[(cyclopropylsukfonyl)amino]carbonyl}-2-ethenylcyclopropyl)-22-(1-methylethyl)-3,23-dioxo-2-oxa-19-thia-4,21,24,28-tetraazapentacyclo[22.2.1.1(4,7).1(17,20).0(6,11)]octacosa-6,8,10,12,17,20(28)-hexaene-25-carboxamide
  参考文献：
  名称：

  Novel Macrocyclic Inhibitors of Hepatitis C NS3/4A Protease Featuring a 2-Amino-1,3-thiazole as a P4 Carbamate Replacement

  摘要：

  Our laboratories recently reported the discovery of P2-P4 macrocyclic inhibitors of HCV NS3/4A protease, characterized by high levels of potency and liver exposure. Within this novel class of inhibitors, we here describe the identification of a structurally diverse series of compounds featuring a 2-amino-1,3-thiazole as replacement of the carbamate in P4. Optimization studies focused on structural modifications in the P3, P2, and P1 regions of the macrocycle as well as on the linker chain and resulted in the discovery of several analogues characterized by excellent levels of enzyme and Cellular activity. Among these, Compound 59 displayed an attractive pharmacokinetic profile in preclinical species and showed sustained liver levels following oral administration in rats.

  DOI：

  10.1021/jm900524b