(3R,5S)-1-((S)-2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoyl)-5-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate | 1285533-27-8

• 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: (3R,5S)-1-((S)-2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoyl)-5-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate
• 英文别名: [(3R,5S)-1-[(2S)-2-(tert-butoxycarbonylamino)-3,3-dimethyl-butanoyl]-5-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinyl-cyclopropyl]carbamoyl]pyrrolidin-3-yl] 4-fluoroisoindoline-2-carboxylate；[(3R,5S)-5-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]-1-[(2S)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]pyrrolidin-3-yl] 4-fluoro-1,3-dihydroisoindole-2-carboxylate
• CAS: 1285533-27-8
• 化学式: C₃₄H₄₆FN₅O₉S
• 分子量: 719.832
• InChiKey: KNRSXDLSSCIKMT-HTFIMNNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  50
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  189
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (3R,5S)-1-((S)-2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoyl)-5-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以85%的产率得到(3R,5S)-1-((S)-2-amino-3,3-dimethylbutanoyl)-5-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate
  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：

  N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-4-([(4-fluoro-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy)-L-proline 在 4-二甲氨基吡啶 、 水 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 NMM 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 (3R,5S)-1-((S)-2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoyl)-5-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate
  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

文献信息

• HCV NS3蛋白酶抑制剂的钠盐
  申请人：正大天晴药业集团股份有限公司

  公开号：CN105315261A

  公开（公告）日：2016-02-10

  本发明公开了HCV？NS3蛋白酶抑制剂的钠盐、其制备方法、其药物组合物及其在预防或治疗丙型肝炎病毒(HCV)感染中的用途。本发明的HCV？NS3蛋白酶抑制剂的钠盐与其他盐相比，具有较好的流动性、更高的稳定性、更好的药代动力学参数。
• [EN] HCV NS3 PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTÉASE NS3 DU VHC
  申请人：RFS PHARMA LLC

  公开号：WO2013106689A8

  公开（公告）日：2014-06-05
• [EN] NOVEL SPECIFIC HCV NS3 PROTEASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS SPÉCIFIQUES DE LA PROTÉASE NS3 DU VHC
  申请人：RFS PHARMA LLC

  公开号：WO2012061248A8

  公开（公告）日：2013-08-01
• NOVEL SPECIFIC HCV NS3 PROTEASE INHIBITORS
  申请人：Courcambeck Jerome

  公开号：US20120129765A1

  公开（公告）日：2012-05-24

  The present invention is directed to compounds, compositions and methods for treating or preventing viral infections, in particular, HCV in human patients or other animal hosts.
• TREATMENT OF HEPATITIS C VIRUS
  申请人：Halfon Philippe

  公开号：US20140135259A1

  公开（公告）日：2014-05-15

  A combined therapy which utilizes hydroxychloroquine and GNS-227: for the treatment of an HCV-related disease, including HCV chronic infection, is disclosed. Further disclosed is pharmaceutical composition (e.g., as a unit dosage form) comprising hydroxychloroquine and GNS-227.