(1-isocyanatocyclohexyl)methyl benzoate | 1207043-94-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1-isocyanatocyclohexyl)methyl benzoate
• CAS: 1207043-94-4
• 化学式: C₁₅H₁₇NO₃
• 分子量: 259.305
• InChiKey: FVJHKHSXAVHUOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.73
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (1R,2S,5S)-N-(4-amino-1-cyclopropyl-3,4-dioxobutan-2-yl)-3-[(2S)-2-amino-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide;hydrochloride 、 (1-isocyanatocyclohexyl)methyl benzoate 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 [1-[[(1S)-1-[(1S,4S,5R)-4-[[3-amino-1-(cyclopropylmethyl)-2,3-dioxo-propyl]carbamoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-2,2-dimethyl-propyl]carbamoylamino]cyclohexyl]methyl benzoate
  参考文献：
  名称：

  Toward the Back-Up of Boceprevir (SCH 503034): Discovery of New Extended P₄-Capped Ketoamide Inhibitors of Hepatitis C Virus NS3 Serine Protease with Improved Potency and Pharmacokinetic Profiles

  摘要：

  Hepatitis C is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically an estimated 300 million people worldwide. Results of Phase I clinical studies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) were encouraging, and thus, additional human clinical studies are underway. 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 and optimization of the P-1' capping led to the discovery of new ketoamide inhibitors of the HCV NS3 serine protease with improved in vitro potency. In addition to being potent inhibitors of HCV subgenomic RNA replication, some of the new P-4-capped inhibitors were also found to have improved PK profile.

  DOI：

  10.1021/jm801632a