(2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide | 1028252-93-8

• 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: (2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide
• 英文别名: (2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yl)oxy-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]pyrrolidine-2-carboxamide
• CAS: 1028252-93-8
• 化学式: C₂₄H₂₇ClN₄O₆S
• 分子量: 535.021
• InChiKey: WSHLAQHWVJPFQB-QQBNPACVSA-N

物化性质

• 密度：
  1.48±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  144
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (2S,4R)-4-[(7-chloro-4-methoxy-1-isoquinolyl)oxy]-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinyl-cyclopropyl]-1-[(2S)-2-[(1-hydroxy-3H-2,1-benzoxaborole-6-carbonyl)amino]-3,3-dimethyl-butanoyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties

  摘要：

  We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.006
• 作为产物：
  描述：

  、 (2S,4r)-4-((7-氯-4-甲氧基异喹啉-1-基)氧基)-2-(((1r,2s)-1-((环丙基磺酰基)氨基甲酰)-2-乙烯基环丙基)氨基甲酰)吡咯烷-1-羧酸叔丁酯 、 盐酸 在 水 、 盐酸 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以provided 6.07 g of (2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide as HCl salt (100%)的产率得到(2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Tripeptides Incorporating Deuterium as Inhibitors of Hepatitis C Virus

  摘要：

  本发明揭示了一种具有通式(I)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丙型肝炎病毒的方法。

  公开号：

  US20140079664A1

文献信息

• Hepatitis C Virus Inhibitors
  申请人：Sin Ny

  公开号：US20080119461A1

  公开（公告）日：2008-05-22

  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.

  抑制丙型肝炎病毒的抑制剂具有一般公式。包含这些化合物的组合物以及使用这些化合物抑制HCV的方法也被披露。
• [EN] TRIPEPTIDES INCORPORATING DEUTERIUM AS INHIBITORS OF HEPATITIS C VIRUS<br/>[FR] TRIPEPTIDES INCORPORANT DU DEUTÉRIUM EN TANT QU'INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012166459A1

  公开（公告）日：2012-12-06

  Hepatitis C virus inhibitors having the general formula (I) [INSERT CHEMICAL STRUCTURE HERE] are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

  本文揭示了具有通式（I）[插入化学结构]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。
• HEPATITIS C VIRUS INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2086963A2

  公开（公告）日：2009-08-12
• TRIPEPTIDES INCORPORATING DEUTERIUM AS INHIBITORS OF HEPATITIS C VIRUS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2726475A1

  公开（公告）日：2014-05-07
• CRYSTALLINE FORMS OF N-(TERT-BUTOXYCARBONYL)-3-METHYL-L-VALYL-(4R)-4-((7-CHLORO-4-METHOXY-1-ISOQUINOLINYL)OXY)-N-((1R,2S)-1-((CYCLOPROPYLSULFONYL)CARBAMOYL)-2-VINYLCYCLOPROPYL)-L-PROLINAMIDE
  申请人：Perrone Robert Kevin

  公开号：US20120230949A1

  公开（公告）日：2012-09-13

  The present disclosure generally relates to crystalline forms of N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-4-((7-chloro-4-methoxy-1-isoquinolinyl)oxy)-N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide. The present disclosure also generally relates to a pharmaceutical composition comprising one or more of the crystalline forms, as well of methods of using the crystalline forms in the treatment of Hepatitis C virus (HCV) and methods for obtaining such crystalline forms.