(2S)-({[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}amino)(1-methylcyclohexyl)acetic acid | 923591-41-7

• 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)-({[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}amino)(1-methylcyclohexyl)acetic acid
• 英文别名: (2S)-2-(2,2-dimethylhex-5-enoxycarbonylamino)-2-(1-methylcyclohexyl)acetic acid
• CAS: 923591-41-7
• 化学式: C₁₈H₃₁NO₄
• 分子量: 325.448
• InChiKey: MWRHBHPLNYCLER-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 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：

  (2S)-({[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}amino)(1-methylcyclohexyl)acetic acid 、 (3R,5S)-5-(methoxycarbonyl)pyrrolidin-3-yl 4-vinyl-1,3-dihydro-2H-isoindole-2-carboxylate hydrochloride 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 N,N-二甲基甲酰胺 为溶剂， 以89%的产率得到(3R,5S)-1-[(2S)-2-({[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}-amino)-2-(1-methylcyclohexyl)acetyl]-5-(methoxycarbonyl)pyrrolidin-3-yl 4-vinyl-1,3-dihydro-2H-isoindole-2-carboxylate
  参考文献：
  名称：

  Discovery of Vaniprevir (MK-7009), a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor

  摘要：

  A new class of H CV NS3/4a protease inhibitors which contain a P2 to P4 macrocyclic constraint was designed using a molecular-modeling derived strategy. Exploration of the P2 heterocyclic region, the P2 to P4 linker, and the PI side chain of this class of compounds via a modular synthetic strategy allowed for the optimization of enzyme potency, cellular activity, and rat liver exposure following oral closing. These studies led to the identification of clinical candidate 35b (vaniprevir, MK-7009), which is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes and has good plasma exposure and excellent liver exposure in multiple species.

  DOI：

  10.1021/jm9015526
• 作为产物：
  描述：

  (S)-2-amino-2-(1-methylcyclohexyl)acetic acid hydrochloride 、 三光气 、 2,2-二甲基-5-己烯-1-醇 在 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 1.08h， 以97%的产率得到(2S)-({[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}amino)(1-methylcyclohexyl)acetic acid
  参考文献：
  名称：

  Discovery of Vaniprevir (MK-7009), a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor

  摘要：

  A new class of H CV NS3/4a protease inhibitors which contain a P2 to P4 macrocyclic constraint was designed using a molecular-modeling derived strategy. Exploration of the P2 heterocyclic region, the P2 to P4 linker, and the PI side chain of this class of compounds via a modular synthetic strategy allowed for the optimization of enzyme potency, cellular activity, and rat liver exposure following oral closing. These studies led to the identification of clinical candidate 35b (vaniprevir, MK-7009), which is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes and has good plasma exposure and excellent liver exposure in multiple species.

  DOI：

  10.1021/jm9015526

文献信息

• 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。
• HCV NS3 PROTEASE INHIBITORS
  申请人：HOLLOWAY M. Katharine

  公开号：US20090124661A1

  公开（公告）日：2009-05-14

  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.

  本发明涉及公式（I）的大环化合物，其可用作丙型肝炎病毒（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。
• US7470664B2
  申请人：——

  公开号：US7470664B2

  公开（公告）日：2008-12-30
• US8216999B2
  申请人：——

  公开号：US8216999B2

  公开（公告）日：2012-07-10
• [EN] HCV NS3 PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTEASE NS3 DU VHC
  申请人：MERCK & CO INC

  公开号：WO2007015855A1

  公开（公告）日：2007-02-08

  [EN] 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.
  [FR] La présente invention concerne des composés macrocycliques représentés par la formule (I) qui sont utiles en tant qu'inhibiteurs de la protéase NS3 du virus de l'hépatite C (VHC), leur synthèse, ainsi que leur utilisation pour le traitement ou la prévention d'infections par le VHC.