(3R,5S)-5-(methoxycarbonyl)pyrrolidin-3-yl 3,4-dihydroisoquinoline-2(1H)-carboxylate hydrochloride | 869994-57-0

• 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: (3R,5S)-5-(methoxycarbonyl)pyrrolidin-3-yl 3,4-dihydroisoquinoline-2(1H)-carboxylate hydrochloride
• CAS: 869994-57-0
• 化学式: C₁₆H₂₀N₂O₄*ClH
• 分子量: 340.807
• InChiKey: USOMIAFBYZFRDZ-DFQHDRSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.51
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.87
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (3R,5S)-5-(methoxycarbonyl)pyrrolidin-3-yl 3,4-dihydroisoquinoline-2(1H)-carboxylate hydrochloride 、 N-Boc-L-叔亮氨酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.25h， 生成 [(3R,5S)-1-[(2S)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]-5-methoxycarbonylpyrrolidin-3-yl] 3,4-dihydro-1H-isoquinoline-2-carboxylate
  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 for treating hepatitis C
  申请人：Albrecht K. Janice

  公开号：US20060276405A1

  公开（公告）日：2006-12-07

  Methods of treating hepatitis C are provided comprising using a therapeutically effective amount of at least one novel hepatitis C (“HCV”) protease inhibitor or, alternatively, at least one antiviral or immuno-modulating HCV agent, which is not an HCV protease inhibitor, for a first treatment period. Subsequently, a combination of the at least one novel hepatitis C (“HCV”) protease inhibitor and the at least one antiviral or immuno-modulating HCV agent are administered in a therapeutically effective amount for a second treatment period. The methods are provided for treating a wide variety of diseases, disorders and symptoms associated with hepatitis C virus by modulating the activity of HCV protease (for example HCV NS3/NS4a serine protease) in a subject.

  提供了治疗丙型肝炎的方法，包括使用至少一种新型丙型肝炎（“HCV”）蛋白酶抑制剂的治疗有效量，或者选择至少一种不是HCV蛋白酶抑制剂的抗病毒或免疫调节HCV药物，用于第一治疗期。随后，在第二治疗期内以治疗有效量给予至少一种新型丙型肝炎（“HCV”）蛋白酶抑制剂和至少一种抗病毒或免疫调节HCV药物的组合。这些方法用于通过调节受试者中HCV蛋白酶（例如HCV NS3/NS4a丝氨酸蛋白酶）的活性来治疗与丙型肝炎病毒相关的各种疾病、疾病和症状。
• 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。
• 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。
• Method for modulating activity of HCV protease through use of a novel HCV protease inhibitor to reduce duration of treatment period
  申请人：Malcolm A. Bruce

  公开号：US20060281689A1

  公开（公告）日：2006-12-14

  Methods are provided for using at least one novel hepatitis C (“HCV”) protease inhibitor in combination with at least one antiviral and/or immunomodulatory agent, which is different from the at least one HCV protease inhibitor, for treating a wide variety of diseases or disorders associated with hepatitis C virus by modulating the activity of HCV protease (for example HCV NS3/NS4a serine protease) and reducing HCV viral load in a subject in a reduced treatment period. With the present invention, a hepatitis C viral load is reduced in a subject to a concentration of less than 6×10 −5 HCV virions per milliliter of plasma in a time period of less than or equal to about 24 weeks. With the present invention, a hepatitis C viral production is suppressed with an effectiveness in a range of 0.7 to 0.997.

  提供了一种方法，使用至少一种新型丙型肝炎（“HCV”）蛋白酶抑制剂与至少一种抗病毒和/或免疫调节剂结合使用，该抗病毒和/或免疫调节剂与至少一种HCV蛋白酶抑制剂不同，用于治疗与丙型肝炎病毒相关的各种疾病或紊乱，通过调节HCV蛋白酶的活性（例如HCV NS3/NS4a丝氨酸蛋白酶）并在较短的治疗期内减少受试者体内的HCV病毒载量。根据本发明，受试者体内的丙型肝炎病毒载量在不超过约24周的时间内降低至每毫升血浆中少于6×10 -5 个HCV病毒颗粒。根据本发明，丙型肝炎病毒的产生被抑制，其有效性范围为0.7至0.997。