methyl (1R,5S)-3-[3,3-dimethyl-1-oxo-2(S)-[[[[1-(tetrahydro-1,1-dioxido-2(R)-thienyl)cyclohexyl]amino]carbonyl]amino]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2(S)-carboxylate | 1220981-65-6

• 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: methyl (1R,5S)-3-[3,3-dimethyl-1-oxo-2(S)-[[[[1-(tetrahydro-1,1-dioxido-2(R)-thienyl)cyclohexyl]amino]carbonyl]amino]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2(S)-carboxylate
• 英文别名: methyl (1R,2S,5S)-3-[(2S)-2-[[1-[(2R)-1,1-dioxothiolan-2-yl]cyclohexyl]carbamoylamino]-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate
• CAS: 1220981-65-6
• 化学式: C₂₆H₄₃N₃O₆S
• 分子量: 525.71
• InChiKey: FUKZHVOAWKFDLS-LJDSDSDDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (1R,5S)-3-[3,3-dimethyl-1-oxo-2(S)-[[[[1-(tetrahydro-1,1-dioxido-2(R)-thienyl)cyclohexyl]amino]carbonyl]amino]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2(S)-carboxylate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 3.17h， 以98%的产率得到(1R,2S,5S)-3-[(2S)-2-[[1-[(2R)-1,1-dioxothiolan-2-yl]cyclohexyl]carbamoylamino]-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylic acid
  参考文献：
  名称：

  Cyclic Sulfones as Novel P3-Caps for Hepatitis C Virus NS3/4A (HCV NS3/4A) Protease Inhibitors: Synthesis and Evaluation of Inhibitors with Improved Potency and Pharmacokinetic Profiles

  摘要：

  HCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to combat the infection. The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and efforts continue for the discovery of more potent compounds with improved pharmacokinetic profiles. A new series of HCV NS3 protease inhibitors having a cyclic sulfone P3-cap have been discovered. Compounds 43 and 44 showed K-i* values in the single-digit nM range and their cellular potency was improved by 10-fold compared to 1. The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration.

  DOI：

  10.1021/jm9016027
• 作为产物：
  描述：

  (1R,2S,5S)-methyl 3-((S)-2-amino-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate hydrochloride 、 (2R)-2-(1-isocyanatocyclohexyl)thiolane 1,1-dioxide 在 N-甲基吗啉 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 以2.06 g的产率得到methyl (1R,5S)-3-[3,3-dimethyl-1-oxo-2(S)-[[[[1-(tetrahydro-1,1-dioxido-2(R)-thienyl)cyclohexyl]amino]carbonyl]amino]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2(S)-carboxylate
  参考文献：
  名称：

  Cyclic Sulfones as Novel P3-Caps for Hepatitis C Virus NS3/4A (HCV NS3/4A) Protease Inhibitors: Synthesis and Evaluation of Inhibitors with Improved Potency and Pharmacokinetic Profiles

  摘要：

  HCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to combat the infection. The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and efforts continue for the discovery of more potent compounds with improved pharmacokinetic profiles. A new series of HCV NS3 protease inhibitors having a cyclic sulfone P3-cap have been discovered. Compounds 43 and 44 showed K-i* values in the single-digit nM range and their cellular potency was improved by 10-fold compared to 1. The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration.

  DOI：

  10.1021/jm9016027