(1S,4S,5R)-3-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethyl-butanoyl]-N-[(1S)-1-[2-(cyclopropylamino)-2-oxo-acetyl]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-4-carboxamide | 856707-12-5

• 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: (1S,4S,5R)-3-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethyl-butanoyl]-N-[(1S)-1-[2-(cyclopropylamino)-2-oxo-acetyl]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-4-carboxamide
• 英文别名: (1R,2S,5S)-3-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-N-[(3S)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
• CAS: 856707-12-5
• 化学式: C₃₆H₅₃N₇O₆
• 分子量: 679.86
• InChiKey: LWRKOOKCHBZLCW-WUIGBPINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  49
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  180
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (1R,2S,5S)-3-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-N-[(3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide 在 戴斯-马丁氧化剂 、 碳酸氢钠 、 sodium thiosulfate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.75h， 生成 (1S,4S,5R)-3-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethyl-butanoyl]-N-[(1S)-1-[2-(cyclopropylamino)-2-oxo-acetyl]butyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-4-carboxamide
  参考文献：
  名称：

  Methods of treating hepatitis C virus

  摘要：

  提供了包括至少一种从本文中定义的I到XXVI式化合物组成的组合物和治疗组合物，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，或在受试者中抑制蛋白酶活性的方法，其中所述化合物在受试者血浆中测量的平均分布体积/生物利用度（Vd/F）大约大于1000升。

  公开号：

  US20060276407A1

文献信息

• Methods of treating hepatitis C virus
  申请人：Gupta K. Samir

  公开号：US20060276406A1

  公开（公告）日：2006-12-07

  Methods for preventing, ameliorating or treating one or more symptoms of Hepatitis C virus (HCV), modulating HCV protease activity and/or inhibiting cathepsin activity in a subject, wherein the methods comprise administering to a subject in need of such treatment a dosage formulation containing at least one compound of Formulae I-XXVI herein, wherein the dosage formulation is capable of maintaining an average Cmin plasma concentration of the compound at or above 10 ng/ml.

  预防、改善或治疗丙型肝炎病毒（HCV）的一个或多个症状的方法，调节受试者中的HCV蛋白酶活性和/或抑制半胱氨酸蛋白酶活性，其中所述方法包括向需要此类治疗的受试者施用含有本文中的至少一种I-XXVI式化合物的剂量配方，其中剂量配方能够维持化合物的平均Cmin血浆浓度在或高于10 ng/ml。
• Medicaments and methods combining a HCV protease inhibitor and an AKR competitor
  申请人：Ghosal Anima

  公开号：US20060276404A1

  公开（公告）日：2006-12-07

  Disclosed are medicaments, pharmaceutical compositions, pharmaceutical kits, and methods based on combinations of a hepatitis C virus (HCV) protease inhibitor and an aldo-keto reductase (AKR) competitor, for concurrent or consecutive administration in treating, preventing, or ameliorating one or more symptoms of HCV, treating disorders associated with HCV, or inhibiting cathepsin activity in a subject.

  揭示了基于丙型肝炎病毒（HCV）蛋白酶抑制剂和醛酮还原酶（AKR）竞争剂的组合的药物、药物组合物、药物套装和方法，用于同时或连续给药以治疗、预防或缓解HCV的一个或多个症状，治疗与HCV相关的疾病，或抑制受试者体内的半胱氨酸蛋白酶活性。
• 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。
• Controlled-release formulation
  申请人：Malcolm A. Bruce

  公开号：US20060275366A1

  公开（公告）日：2006-12-07

  Controlled-release dosage formulations including at least one compound of Formulae I to XXVI herein and a controlled-release carrier and methods of treatment using the same are provided.

  提供了包括本文中的至少一种I到XXVI式化合物和控释载体的控释剂量制剂，以及使用它们的治疗方法。
• Administration of HCV protease inhibitors in combination with food to improve bioavailability
  申请人：Zhang Jenny

  公开号：US20060281688A1

  公开（公告）日：2006-12-14

  Methods of treating, preventing or ameliorating one or more symptoms of hepatitis C in a subject comprising the step of administering at least one HCV protease inhibitor in combination with food are provided. Also provided are methods of increasing bioavailability of an HCV protease inhibitor and methods of increasing serum levels of an HCV protease inhibitor in a subject. All methods comprise adminstering at least one HCV protease inhibitor in combination with food, the at least one HCV protease inhibitor selected from the group consisting of compounds of Formulae I-XXVI, described herein. Administration of compounds of the present invention in combination with food provides improved bioavailability and increased peak serum levels of the compounds as compared to administration without food.

  提供了一种治疗、预防或改善乙型肝炎患者一种或多种症状的方法，包括在给予患者至少一种HCV蛋白酶抑制剂的步骤中与食物结合。还提供了一种增加HCV蛋白酶抑制剂生物利用度的方法和增加患者血清中HCV蛋白酶抑制剂水平的方法。所有方法包括在与食物结合的情况下给予患者至少一种HCV蛋白酶抑制剂，所述至少一种HCV蛋白酶抑制剂选自本文所述的化合物I-XXVI的组。与不与食物一起给药相比，本发明化合物与食物结合给药提供了改善的生物利用度和增加的化合物峰值血清水平。