(S)-1-(1-(((S)-tert-butylsulfinyl)amino)cyclohexyl)-N,N-dimethylethane-1-sulfonamide | 1222186-23-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机硫酸及其衍生物
• 英文名称: (S)-1-(1-(((S)-tert-butylsulfinyl)amino)cyclohexyl)-N,N-dimethylethane-1-sulfonamide
• CAS: 1222186-23-3
• 化学式: C₁₄H₃₀N₂O₃S₂
• 分子量: 338.536
• InChiKey: WSSGXBDKSRAIEE-YUNKPMOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  66.48
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  (S)-N-cyclohexylidene-2-methylpropane-2-sulfinamide 、 N,N-二甲基乙硫胺 在 正丁基锂 作用下， 以 甲苯 为溶剂， 生成 (S)-1-(1-(((S)-tert-butylsulfinyl)amino)cyclohexyl)-N,N-dimethylethane-1-sulfonamide 、 (R)-1-(1-(((S)-tert-butylsulfinyl)amino)cyclohexyl)-N,N-dimethylethane-1-sulfonamide
  参考文献：
  名称：

  Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles in preclinical species

  摘要：

  Hepatitis is a disease characterized by inflammation of the liver, usually producing swelling and, in many cases, permanent damage to liver tissues. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically 3% of the world's population. Boceprevir, SCH 503034, (1) our first generation HCV inhibitor, has already established proof-of-concept and is currently in late stage (phase III) clinical trials. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P-4 pocket by introducing a new sulfonamide moiety and optimization of the P1/P-1' capping led to the discovery of a novel series of inhibitors of the HCV NS3 serine protease. Optimization of the P-1 residue significantly improved potency and selectivity. The combination of optimal moieties led to the discovery of compound 47 which, in addition to being a potent inhibitor of HCV subgenomic RNA replication, was also found to have good PK profile in rat, dog and monkey. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.01.044