N-[(hex-5-en-1-yloxy)carbonyl]-3-methyl-L-valine | 923591-18-8

• 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: N-[(hex-5-en-1-yloxy)carbonyl]-3-methyl-L-valine
• 英文别名: 3-methyl-N-[(hex-5-enyloxy)carbonyl]-L-valine；(S)-2-((hex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoic acid；N-{[(Hex-5-en-1-yl)oxy]carbonyl}-3-methyl-L-valine；(2S)-2-(hex-5-enoxycarbonylamino)-3,3-dimethylbutanoic acid
• CAS: 923591-18-8
• 化学式: C₁₃H₂₃NO₄
• 分子量: 257.33
• InChiKey: HGLGPVAXXFHTGG-SNVBAGLBSA-N

物化性质

• 沸点：
  403.2±38.0 °C(Predicted)
• 密度：
  1.047±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[(hex-5-en-1-yloxy)carbonyl]-3-methyl-L-valine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 palladium on activated charcoal 、 氢气 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 4.0h， 生成 (2R,4S,7S)-7-tert-butyl-N-[(1R,2S)-2-cyclopropyl-1-(cyclopropylsulfonylcarbamoyl)cyclopropyl]-2,18-dimethoxy-6,9-dioxo-10-oxa-5,8-diazatetracyclo[15.5.3.12,5.020,24]hexacosa-1(23),17,19,21,24-pentaene-4-carboxamide
  参考文献：
  名称：

  The discovery and optimization of naphthalene-linked P2-P4 Macrocycles as inhibitors of HCV NS3 protease

  摘要：

  Naphthalene-linked P2-P4 macrocycles within a tri-peptide-based acyl sulfonamide chemotype have been synthesized and found to inhibit HCV NS3 proteases representing genotypes 1a and 1b with single digit nanomolar potency. The pharmacokinetic profile of compounds in this series was optimized through structural modifications along the macrocycle tether as well as the P1 subsite. Ultimately a compound with oral bioavailability of 100% in rat, and a long half-life in plasma was obtained. However, compounds in this macrocyclic series exhibited cardiac effects in an isolated rabbit heart model and for this reason further optimization efforts were discontinued. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.005
• 作为产物：
  描述：

  L-叔亮氨酸 、 Hex-5-enyl hydrogen carbonate 在 三光气 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 4.08h， 生成 N-[(hex-5-en-1-yloxy)carbonyl]-3-methyl-L-valine
  参考文献：
  名称：

  The discovery and optimization of naphthalene-linked P2-P4 Macrocycles as inhibitors of HCV NS3 protease

  摘要：

  Naphthalene-linked P2-P4 macrocycles within a tri-peptide-based acyl sulfonamide chemotype have been synthesized and found to inhibit HCV NS3 proteases representing genotypes 1a and 1b with single digit nanomolar potency. The pharmacokinetic profile of compounds in this series was optimized through structural modifications along the macrocycle tether as well as the P1 subsite. Ultimately a compound with oral bioavailability of 100% in rat, and a long half-life in plasma was obtained. However, compounds in this macrocyclic series exhibited cardiac effects in an isolated rabbit heart model and for this reason further optimization efforts were discontinued. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.005

文献信息

• Macrocyclic Heterocyclic Compound for Inhibiting Hepatitis C Virus and Preparation and Use Thereof
  申请人：Zhan Zheng-yun James

  公开号：US20140205567A1

  公开（公告）日：2014-07-24

  The present invention discloses a class of novel macro-heterocyclic compounds represented by the formula Ia or Ib, and their intermediates, preparation methods and the uses. The macro-heterocyclic compounds of the present invention have good inhibitory activities against hepatitis C virus (HCV), and can be used to treat HCV infection effectively by its excellent inhibition against HCV, low toxicity and side effects.

  本发明公开了一类新型大环杂环化合物，其代表性结构式为Ia或Ib，及其中间体、制备方法和用途。本发明的大环杂环化合物对丙型肝炎病毒（HCV）具有良好的抑制活性，凭借其对HCV的优异抑制作用、低毒性和副作用，能有效用于治疗HCV感染。
• [EN] QUINOXALINE-CONTAINING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS<br/>[FR] COMPOSÉS CONTENANT DE LA QUINOXALINE EN TANT QU'INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：ENANTA PHARM INC

  公开号：WO2009064975A1

  公开（公告）日：2009-05-22

  The present invention discloses compounds of formula I and II or pharmaceutically acceptable salts, esters, or prodrugs thereof which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明公开了抑制丝氨酸蛋白酶活性的I和II公式化合物，或其药物可接受的盐、酯或前药，尤其是抑制丙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰丙型肝炎病毒的生命周期，并且也用作抗病毒剂。本发明进一步涉及包含前述化合物的药物组合物，用于给患有HCV感染的主体进行管理。本发明还涉及通过管理包含本发明化合物的药物组合物来治疗主体中的HCV感染的方法。
• HCV NS3 protease inhibitors
  申请人：Holloway Katharine M.

  公开号：US20070027071A1

  公开（公告）日：2007-02-01

  The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

  本发明涉及一种公式（I）的大环化合物，该化合物可用作乙型肝炎病毒（HCV）NS3蛋白酶的抑制剂，其合成以及用于治疗或预防HCV感染的用途。
• Hepatitis C Virus Inhibitors
  申请人：Hiebert Sheldon

  公开号：US20100080770A1

  公开（公告）日：2010-04-01

  Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

  揭示了具有一般式的丙型肝炎病毒抑制剂。还揭示了包含这些化合物的组合物以及使用这些化合物抑制HCV的方法。
• [EN] TRIAZOLE-CONTAINING MACROCYCLIC HCV SERINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS MACROCYCLIQUES CONTENANT DU TRIAZOLE DES PROTÉASES À SÉRINE DU VHC
  申请人：ENANTA PHARM INC

  公开号：WO2009079353A1

  公开（公告）日：2009-06-25

  The present invention discloses compounds of formula I, II and III or pharmaceutically acceptable salts, esters, or prodrugs thereof, which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明揭示了化合物I、II和III或其药学上可接受的盐、酯或前药，其可抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰了乙型肝炎病毒的生命周期，也可用作抗病毒剂。本发明还涉及包含上述化合物的制药组合物，用于治疗患有HCV感染的受试者。本发明还涉及通过给予含有本发明化合物的制药组合物来治疗受试者的HCV感染的方法。