(1s,3ar,6as)-1-乙基-2-(苯基甲基)酯 | 402958-21-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (1s,3ar,6as)-1-乙基-2-(苯基甲基)酯
• 英文名称: (1S,3aR,6aS)-4-Oxo-hexahydro-cyclopenta[c]pyrrole-1,2-dicarboxylic acid 2-benzyl ester 1-ethyl ester
• 英文别名: (1R,3aS,6aR)-rel-2-Benzyl 1-ethyl 4-oxohexahydrocyclopenta[c]pyrrole-1,2(1H)-dicarboxylate；2-O-benzyl 3-O-ethyl (3S,3aS,6aR)-6-oxo-1,3,3a,4,5,6a-hexahydrocyclopenta[c]pyrrole-2,3-dicarboxylate
• CAS: 402958-21-8
• 化学式: C₁₈H₂₁NO₅
• 分子量: 331.368
• InChiKey: VFGHIBHHMQQACC-DZKIICNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1s,3ar,6as)-1-乙基-2-(苯基甲基)酯 在 sodium tetrahydroborate 、 溶剂黄146 、 碳酸氢钠 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 0.5h， 以92%的产率得到2-O-benzyl 3-O-ethyl (3S,3aS,6aR)-6-hydroxy-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-2,3-dicarboxylate
  参考文献：
  名称：

  3,4-(cyclopentyl)-fused proline compounds as inhibitors of hepatitis C virus NS3 serine protease

  摘要：

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施方式中，本发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。

  公开号：

  US20050197301A1
• 作为产物：
  描述：

  3-(Ethoxycarbonylmethyl)-5-(2-hydroxyethyl)-4-methylthiazolium Bromide 在 偶氮二异丁腈 、 三正丁基氢锡 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.0h， 生成 (1s,3ar,6as)-1-乙基-2-(苯基甲基)酯
  参考文献：
  名称：

  一种特拉匹韦中间体的制备方法

  摘要：

  本发明公开了一种特拉匹韦中间体的制备方法，所述特拉匹韦中间体为式I化合物，其包括如下反应路线：其中：R选自C1～C4烷基；R1选自氢、C1～C8烷基、C1～C8烷氧基、C6～C12芳基、烷基磺酰基、C6～C12芳基磺酰基或取代的C6～C12芳基磺酰基；P为氨基保护基。本发明方法具有操作简单、安全无污染、对设备无特殊要求、生产成本低、收率高等优点，适合规模化生产，对实现特拉匹韦的工业化具有极强的实用价值。

  公开号：

  CN106928123A

文献信息

• Peptidomimetic protease inhibitors
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2368878A1

  公开（公告）日：2011-09-28

  The present invention relates to peptidomimetic compounds useful as protease inhibitors (1), particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及肽类似物化合物，用作蛋白酶抑制剂（1），特别是丝氨酸蛋白酶抑制剂，更特别是丙型肝炎NS3蛋白酶抑制剂；中间体；它们的制备，包括到中间体的新型立体选择性过程。本发明还涉及制药组合物和使用这些化合物抑制HCV蛋白酶或治疗患有HCV感染或与感染相关的生理状况的患者的方法。还提供了药物组合物，其中除了一个或多个HCV丝氨酸蛋白酶抑制剂外，还包括一个或多个表现出抗HCV活性的干扰素和/或一个或多个具有抗HCV活性的化合物和一种药学上可接受的载体，并使用这些组合物治疗或预防患者的HCV感染的方法。本发明还涉及用于治疗或预防患者的HCV感染的套件或药物包。
• PEPTIDOMIMETIC PROTEASE INHIBITORS
  申请人：BABINE ROBERT EDWARD

  公开号：US20120282219A1

  公开（公告）日：2012-11-08

  The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel stereoselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及肽类似物化合物，作为蛋白酶抑制剂，特别是作为丝氨酸蛋白酶抑制剂，更特别是作为丙型肝炎NS3蛋白酶抑制剂；以及其中间体；它们的制备，包括新的对中间体的立体选择性过程。本发明还涉及制药组合物，以及使用这些化合物抑制HCV蛋白酶或治疗患有HCV感染或与感染相关的生理状况的患者的方法。还提供了药物组合物，其中除了一个或多个HCV丝氨酸蛋白酶抑制剂外，还包括一个或多个表现出抗HCV活性的干扰素和/或一个或多个具有抗HCV活性的化合物和一种药学上可接受的载体，并使用这些组合物来治疗或预防患者的HCV感染。本发明还涉及用于治疗或预防患者HCV感染的工具包或药物包。
• Chiral intermediates for the preparation of peptidomimetic protease inhibitors
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2368877A1

  公开（公告）日：2011-09-28

  The present invention relates to peptidomimetic compounds useful as protease inhibitors (1), particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及可用作蛋白酶抑制剂（1），特别是丝氨酸蛋白酶抑制剂，更特别是丙型肝炎 NS3 蛋白酶抑制剂的拟肽化合物；其中间体；其制备方法，包括制备中间体的新型立体选择性工艺。本发明还涉及药物组合物以及使用这些化合物抑制 HCV 蛋白酶或治疗 HCV 感染患者或与感染相关的生理状况的方法。本发明还提供了药物组合物，除一种或多种HCV丝氨酸蛋白酶抑制剂外，还包括一种或多种具有抗HCV活性的干扰素和/或一种或多种具有抗HCV活性的化合物和药学上可接受的载体，以及使用该组合物治疗或预防患者HCV感染的方法。本发明还涉及一种用于治疗或预防患者HCV感染的试剂盒或药包。
• Discovery of a novel bicycloproline P2 bearing peptidyl α-ketoamide LY514962 as HCV protease inhibitor
  作者：Yvonne Yip、Frantz Victor、Jason Lamar、Robert Johnson、Q.May Wang、Donna Barket、John Glass、Ling Jin、Lifei Liu、Daryl Venable、Mark Wakulchik、Congping Xie、Beverly Heinz、Elcira Villarreal、Joe Colacino、Nathan Yumibe、Mark Tebbe、John Munroe、Shu-Hui Chen

  DOI：10.1016/j.bmcl.2003.09.074

  日期：2004.1

  We describe herein the design, syntheses and evaluation of a number of bicycloproline P2 bearing HCV protease inhibitors endowed with impressive enzyme potency, enzyme selectivity, cellular activity and favorable ADME profiles. (C) 2003 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of tripeptidyl α-Ketoamides as human rhinovirus 3C protease inhibitors
  作者：Shu-Hui Chen、Jason Lamar、Frantz Victor、Nancy Snyder、Robert Johnson、Beverly A. Heinz、Mark Wakulchik、Q.May Wang

  DOI：10.1016/s0960-894x(03)00753-4

  日期：2003.10

  We describe herein the synthesis and biological evaluation of a series of tripeptidyl alpha-ketoamides as human rhinovirus (HRV) 3C protease inhibitors. The most potent inhibitor discussed in this manuscript, 41, exhibited impressive enzyme inhibitory activity as well as antiviral activity against HRV-14. (C) 2003 Elsevier Ltd. All rights reserved.