(2S)-2-[[(2S)-3-cyclohexyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]-3,3-dimethylbutanoic acid | 402959-43-7

• 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: (2S)-2-[[(2S)-3-cyclohexyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]-3,3-dimethylbutanoic acid
• CAS: 402959-43-7
• 化学式: C₂₀H₃₀N₄O₄
• 分子量: 390.483
• InChiKey: VXPPSLHLIAGCLM-GOEBONIOSA-N

物化性质

• 沸点：
  682.2±55.0 °C(Predicted)
• 密度：
  1.175±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S)-2-[[(2S)-3-cyclohexyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]-3,3-dimethylbutanoic acid 在 sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (3S,3aS,6aR)-2-[(2S)-2-[[(2S)-3-cyclohexyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]-3,3-dimethylbutanoyl]-N-[1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide
  参考文献：
  名称：

  P4 and P1′ optimization of bicycloproline P2 bearing tetrapeptidyl α-ketoamides as HCV protease inhibitors

  摘要：

  With the aim of improving HCV protease inhibitors reported in our previous manuscripts, we synthesized and evaluated a series of la-based tetrapeptidyl alpha-ketoamides with additional P4 modification. The promising analog discovered through this SAR, 5a, was further derivatized at P1' or P1 position. As a result of these efforts, we found that replacement of the P4 valine as seen in 1a with cyclohexylglycine (Chg) resulted in the discovery of 5a, 5c, and 5e endowed with improved cellular activity in comparison to 1a. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.007
• 作为产物：
  描述：

  丁氧羰基--环乙基-丙氨酸-羟基盐酸盐 在 盐酸 、 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 生成 (2S)-2-[[(2S)-3-cyclohexyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]-3,3-dimethylbutanoic acid
  参考文献：
  名称：

  P4 and P1′ optimization of bicycloproline P2 bearing tetrapeptidyl α-ketoamides as HCV protease inhibitors

  摘要：

  With the aim of improving HCV protease inhibitors reported in our previous manuscripts, we synthesized and evaluated a series of la-based tetrapeptidyl alpha-ketoamides with additional P4 modification. The promising analog discovered through this SAR, 5a, was further derivatized at P1' or P1 position. As a result of these efforts, we found that replacement of the P4 valine as seen in 1a with cyclohexylglycine (Chg) resulted in the discovery of 5a, 5c, and 5e endowed with improved cellular activity in comparison to 1a. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.007

文献信息

• PHARMACEUTICAL COMPOSITIONS USEFUL FOR TREATING HCV
  申请人：Delaney William E.

  公开号：US20100324059A1

  公开（公告）日：2010-12-23

  This invention relates to combinations of Compound 1 and Compound 2 which are useful for treating hepatitis C virus infection.

  这项发明涉及一种用于治疗丙型肝炎病毒感染的化合物1和化合物2的组合物。
• Peptidomimetic protease inhibitors
  申请人：Babine Robert Edward

  公开号：US20100137583A1

  公开（公告）日：2010-06-03

  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 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.

  本发明涉及用作蛋白酶抑制剂的肽类模拟化合物，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；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和使用该化合物抑制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，其中包括除一种或多种HCV丝氨酸蛋白酶抑制剂外，还包括一种或多种表现出抗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可接受载体，并使用该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HCV感染的工具包或药品包。
• 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。
• Peptidomimetic protease inhibitors and intermediates for their preparation As treatment for HCV infection
  申请人：Vertex Pharmaceuticals Inc.

  公开号：EP2368877B1

  公开（公告）日：2014-05-07
• US7820671B2
  申请人：——

  公开号：US7820671B2

  公开（公告）日：2010-10-26