N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-4-(1-isoquinolinolinyloxy)-L-proline | 1140736-58-8

• 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-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-4-(1-isoquinolinolinyloxy)-L-proline
• 英文别名: (2S,4R)-1-[(2S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl]-4-isoquinolin-1-yloxypyrrolidine-2-carboxylic acid
• CAS: 1140736-58-8
• 化学式: C₂₆H₃₃N₃O₆
• 分子量: 483.565
• InChiKey: NGKQLPOZWGWNSW-HLAWJBBLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-amino-1,2-oxaborinan-2-ol hydrochloride 、 N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-4-(1-isoquinolinolinyloxy)-L-proline 在 N-甲基吗啉 、 三乙胺 、 氯甲酸异丁酯 作用下， 生成 N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-(2-hydroxy-1,2-oxaborinan-3-yl)-4-(1-isoquinolinyloxy)-L-prolinamide
  参考文献：
  名称：

  Synthesis and evaluation of novel α-amino cyclic boronates as inhibitors of HCV NS3 protease

  摘要：

  We have designed and synthesized a novel series of alpha-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described.

  DOI：

  10.1016/j.bmcl.2010.04.129
• 作为产物：
  描述：

  (2S,4R)-1-((S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl)-4-hydroxy-pyrrolidine-2-carboxylic acid 、 1-氯异喹啉 在 potassium tert-butylate 、 盐酸 作用下， 以 二甲基亚砜 、 水 为溶剂， 反应 1.0h， 生成 N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-4-(1-isoquinolinolinyloxy)-L-proline
  参考文献：
  名称：

  [EN] NOVEL CYCLIC BORONATE INHIBITORS OF HCV REPLICATION
  [FR] NOUVEAUX INHIBITEURS DE BORONATE CYCLIQUES DE RÉPLICATION DU VIRUS DE L'HÉPATITE C

  摘要：

  提供了化学式（I）的化合物或其盐；其中R1、R2、R3、R4、R6、R8、R20、R30、Y、Z和n的定义如描述中所述。还公开了将这些化合物用作药物以及用于治疗病毒感染，特别是HCV感染的药物制造中的用途。该发明还包括制备这些化合物和其药物配方的过程。

  公开号：

  WO2009046098A1

文献信息

• [EN] NOVEL CYCLIC BORONATE INHIBITORS OF HCV REPLICATION<br/>[FR] NOUVEAUX INHIBITEURS DE BORONATE CYCLIQUES DE RÉPLICATION DU VIRUS DE L'HÉPATITE C
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009046098A1

  公开（公告）日：2009-04-09

  Compounds of formula (I) or a salt thereof are provided; wherein R1, R2, R3, R4, R6, R8, R20, R30, Y, Z and n are as defined in the description. Uses of the compounds as medicaments, and in the manufacture of medicaments for treating viral infection, especially HCV infection are also disclosed. The invention further comprises processes to make these compounds and pharmaceutical formulations thereof.

  提供了化学式（I）的化合物或其盐；其中R1、R2、R3、R4、R6、R8、R20、R30、Y、Z和n的定义如描述中所述。还公开了将这些化合物用作药物以及用于治疗病毒感染，特别是HCV感染的药物制造中的用途。该发明还包括制备这些化合物和其药物配方的过程。
• Synthesis and evaluation of novel α-amino cyclic boronates as inhibitors of HCV NS3 protease
  作者：Xianfeng Li、Yong-Kang Zhang、Yang Liu、Charles Z. Ding、Qun Li、Yasheen Zhou、Jacob J. Plattner、Stephen J. Baker、Xuelei Qian、Dazhong Fan、Liang Liao、Zhi-Jie Ni、Gemma V. White、Jackie E. Mordaunt、Linos X. Lazarides、Martin J. Slater、Richard L. Jarvest、Pia Thommes、Malcolm Ellis、Colin M. Edge、Julia A. Hubbard、Don Somers、Paul Rowland、Pamela Nassau、Bill McDowell、Tadeusz J. Skarzynski、Wieslaw M. Kazmierski、Richard M. Grimes、Lois L. Wright、Gary K. Smith、Wuxin Zou、Jon Wright、Lewis E. Pennicott

  DOI：10.1016/j.bmcl.2010.04.129

  日期：2010.6

  We have designed and synthesized a novel series of alpha-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described.