H-Gly(tBu)-Oic-OtBu | 615583-06-7

• 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: H-Gly(tBu)-Oic-OtBu
• 英文别名: tert-butyl (2S,3aS,7aS)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylate
• CAS: 615583-06-7
• 化学式: C₁₉H₃₄N₂O₃
• 分子量: 338.491
• InChiKey: DXRZZJPHBOKEBI-ZQDZILKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  H-Gly(tBu)-Oic-OtBu 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 (2S,3aS,7aS)-1-((S)-2-((S)-2-cyclohexyl-2-(1H-pyrrole-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)octahydro-1H-indole-2-carboxamide
  参考文献：
  名称：

  Inhibitors of hepatitis C virus NS3·4A protease. Effect of P4 capping groups on inhibitory potency and pharmacokinetics

  摘要：

  Reversible tetrapeptide-based compounds have been shown to effectively inhibit the hepatitis C virus NS3 center dot 4A protease. Inhibition of viral replicon RNA production in Huh-7 cells has also been demonstrated. We show herein that the inclusion of hydrogen bond donors on the P4 capping group of tetrapeptide-based inhibitors result in increased binding potency to the NS3 center dot 4A protease. The capping groups also impart significant effects on the pharmacokinetic profile of these inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.090
• 作为产物：
  描述：

  (2S, 3aS, 7aS) 2-t.butoxycarbonyl perhydroindole 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 H-Gly(tBu)-Oic-OtBu
  参考文献：
  名称：

  Inhibitors of hepatitis C virus NS3·4A protease. Effect of P4 capping groups on inhibitory potency and pharmacokinetics

  摘要：

  Reversible tetrapeptide-based compounds have been shown to effectively inhibit the hepatitis C virus NS3 center dot 4A protease. Inhibition of viral replicon RNA production in Huh-7 cells has also been demonstrated. We show herein that the inclusion of hydrogen bond donors on the P4 capping group of tetrapeptide-based inhibitors result in increased binding potency to the NS3 center dot 4A protease. The capping groups also impart significant effects on the pharmacokinetic profile of these inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.090

文献信息

• Inhibitors of serine proteases, particular HCV NS3-NS4A protease
  申请人：Pitlik Janos

  公开号：US20070292933A1

  公开（公告）日：2007-12-20

  The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

  本发明涉及抑制丝氨酸蛋白酶活性的化合物，特别是乙型肝炎病毒NS3-NS4A蛋白酶的活性。因此，它们通过干扰乙型肝炎病毒的生命周期而起作用，并且也可用作抗病毒剂。本发明还涉及包含这些化合物的组合物，无论是用于体外使用还是用于治疗患有HCV感染的患者的给药。本发明还涉及通过给予含有本发明化合物的组合物来治疗患有HCV感染的患者的方法。本发明还涉及制备这些化合物的过程。
• INHIBITORS OF SERINE PROTEASES, PARTICULARLY HCV NS3-NS4A PROTEASE
  申请人：Pitlik Janos

  公开号：US20100173851A1

  公开（公告）日：2010-07-08

  The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

  本发明涉及抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒NS3-NS4A蛋白酶活性的化合物。因此，它们通过干扰丙型肝炎病毒的生命周期发挥作用，并且也可用作抗病毒剂。本发明还涉及包含这些化合物的组合物，无论是用于体外使用还是用于治疗HCV感染的患者的给药。本发明还涉及通过给予含有本发明化合物的组合物来治疗患者的HCV感染的方法。本发明还涉及制备这些化合物的方法。
• Inhibitors of serine proteases, particularly HCV NS3-NS4A protease
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2468744A2

  公开（公告）日：2012-06-27

  The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

  本发明涉及抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒 NS3-NS4A 蛋白酶活性的化合物。因此，它们通过干扰丙型肝炎病毒的生命周期发挥作用，也可用作抗病毒药物。本发明还涉及包含这些化合物的组合物，这些组合物可用于体内外使用，也可用于丙型肝炎病毒感染患者。本发明还涉及通过施用包含本发明化合物的组合物治疗患者 HCV 感染的方法。本发明还涉及制备这些化合物的工艺。
• US7273885B2
  申请人：——

  公开号：US7273885B2

  公开（公告）日：2007-09-25
• Inhibitors of hepatitis C virus NS3·4A protease. Effect of P4 capping groups on inhibitory potency and pharmacokinetics
  作者：Robert B. Perni、Gurudatt Chandorkar、Kevin M. Cottrell、Cynthia A. Gates、Chao Lin、Kai Lin、Yu-Ping Luong、John P. Maxwell、Mark A. Murcko、Janos Pitlik、Govinda Rao、Wayne C. Schairer、John Van Drie、Yunyi Wei

  DOI：10.1016/j.bmcl.2007.03.090

  日期：2007.6

  Reversible tetrapeptide-based compounds have been shown to effectively inhibit the hepatitis C virus NS3 center dot 4A protease. Inhibition of viral replicon RNA production in Huh-7 cells has also been demonstrated. We show herein that the inclusion of hydrogen bond donors on the P4 capping group of tetrapeptide-based inhibitors result in increased binding potency to the NS3 center dot 4A protease. The capping groups also impart significant effects on the pharmacokinetic profile of these inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.