(16aS,17aR,17bS)-13(S)-[[[[1(S)-[[[(dimethylamino)sulfonyl]methylamino]methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]octadecahydro-17,17-dimethyl-α,1,14-trioxo-N-(2-propenyl)-2H-cyclopropa[3,4]pyrrolo[1,2-a][1,4]diazacyclohexadecine-3(S)-acetamide | 1100795-74-1

• 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: (16aS,17aR,17bS)-13(S)-[[[[1(S)-[[[(dimethylamino)sulfonyl]methylamino]methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]octadecahydro-17,17-dimethyl-α,1,14-trioxo-N-(2-propenyl)-2H-cyclopropa[3,4]pyrrolo[1,2-a][1,4]diazacyclohexadecine-3(S)-acetamide
• 英文别名: 2-[(3S,13S,16S,17R,19S)-3-({[(2S)-1-[(dimethylsulfamoyl)(methyl)amino]-3,3-dimethylbutan-2-yl]carbamoyl}amino)-18,18-dimethyl-2,15-dioxo-1,14-diazatricyclo[14.4.0.0^{17,19}]icosan-13-yl]-2-oxo-N-(prop-2-en-1-yl)acetamide；2-[(3S,13S,16S,17R,19S)-3-[[(2S)-1-[dimethylsulfamoyl(methyl)amino]-3,3-dimethylbutan-2-yl]carbamoylamino]-18,18-dimethyl-2,15-dioxo-1,14-diazatricyclo[14.4.0.017,19]icosan-13-yl]-2-oxo-N-prop-2-enylacetamide
• CAS: 1100795-74-1
• 化学式: C₃₅H₆₁N₇O₇S
• 分子量: 723.978
• InChiKey: ZRJWAVAFJOLRCZ-XDHPVKSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  50
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  186
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (2S)-N-(dimethylsulfamoyl)-2-isocyanato-N,3,3-trimethylbutan-1-amine 、 2-[(3S,13S,16S,17R,19S)-3-amino-18,18-dimethyl-2,15-dioxo-1,14-diazatricyclo[14.4.0.017,19]icosan-13-yl]-2-oxo-N-prop-2-enylacetamide 在 N-甲基吗啉 作用下， 以 二氯甲烷 为溶剂， 生成 (16aS,17aR,17bS)-13(S)-[[[[1(S)-[[[(dimethylamino)sulfonyl]methylamino]methyl]-2,2-dimethylpropyl]amino]carbonyl]amino]octadecahydro-17,17-dimethyl-α,1,14-trioxo-N-(2-propenyl)-2H-cyclopropa[3,4]pyrrolo[1,2-a][1,4]diazacyclohexadecine-3(S)-acetamide
  参考文献：
  名称：

  Discovery and Structure−Activity Relationship of P₁−P₃ Ketoamide Derived Macrocyclic Inhibitors of Hepatitis C Virus NS3 Protease

  摘要：

  Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, and affects more than 200 million people worldwide. Although combination therapy of interferon-alpha and ribavirin is reasonably successful in treating majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of a series of ketoamide derived P-1-P-3 macrocyclic inhibitors that are more potent than the first generation clinical candidate, boceprevir (1, Sch 503034), is discussed. The optimization of these macrocyclic inhibitors identified a P-3 imide capped analogue 52 that was 20 times more potent than 1 and demonstrated good oral pharmacokinetics in rats. X-ray structure of 52 bound to NS3 protease and biological data are also discussed.

  DOI：

  10.1021/jm800940u

文献信息

• Liver/plasma concentration ratio for dosing hepatitis C virus protease inhibitor
  申请人：White E. Ronald

  公开号：US20070021351A1

  公开（公告）日：2007-01-25

  Compositions and therapeutic combinations are provided including at least one compound selected from the group consisting of compounds of Formulae I to XXVI as defined herein as well as methods of treatment, prevention or amelioration of one or more symptoms of hepatitis C, treating disorders associated with HCV virus, modulating activity of HCV protease, in which liver to plasma concentration ratio of the compound ranges from about 2:1 to about 10:1.

  提供了包括至少一种从本文中定义的I到XXVI式化合物组中选择的化合物的组合物和治疗组合，以及治疗、预防或改善丙型肝炎的一个或多个症状的方法，治疗与HCV病毒相关的疾病，调节HCV蛋白酶活性，其中化合物的肝脏到血浆浓度比范围约为2:1至约为10:1。
• Pharmaceutical formulations and methods of treatment using the same
  申请人：Malcolm A. Bruce

  公开号：US20070010431A1

  公开（公告）日：2007-01-11

  Pharmaceutical formulations containing at least one compound of Formulae I-XXVI herein and at least one surfactant. Pharmaceutically acceptable carriers and excipients may also be included in the formulations. The formulations of the present invention are suited for use in single unit dosages.

  含有本文中的至少一种I-XXVI式化合物和至少一种表面活性剂的制药配方。 制剂中还可以包括药用可接受的载体和辅料。 本发明的制剂适用于单剂量使用。
• Controlled-release formulation of HCV protease inhibitor and methods using the same
  申请人：Malcolm A. Bruce

  公开号：US20070237818A1

  公开（公告）日：2007-10-11

  Controlled-release dosage formulations including at least one compound of Formulae I to XXVIII herein and a controlled-release carrier and methods of treatment using the same are provided.
• Macrocyclic Inhibitors of Hepatitis C Virus NS3 Serine Protease
  申请人：Venkatraman Srikanth

  公开号：US20110150835A1

  公开（公告）日：2011-06-23

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.
• US7592419B2
  申请人：——

  公开号：US7592419B2

  公开（公告）日：2009-09-22