1-benzyloxycarbonyl-3-isocyanato-5-trifIuoromethylindole-2-carboxylic acid tert-butyl ester | 1154603-18-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-benzyloxycarbonyl-3-isocyanato-5-trifIuoromethylindole-2-carboxylic acid tert-butyl ester
• 英文别名: 1-Benzyloxycarbonyl-3-isocyanato-5-trifluoromethylindole-2-carboxylic acid tert-butyl ester；1-O-benzyl 2-O-tert-butyl 3-isocyanato-5-(trifluoromethyl)indole-1,2-dicarboxylate
• CAS: 1154603-18-5
• 化学式: C₂₃H₁₉F₃N₂O₅
• 分子量: 460.409
• InChiKey: CXFRRVWJJBZARN-UHFFFAOYSA-N

物化性质

• 沸点：
  554.0±60.0 °C(predicted)
• 密度：
  1.30±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  87
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-benzyloxycarbonyl-3-isocyanato-5-trifIuoromethylindole-2-carboxylic acid tert-butyl ester 在 potassium tert-butylate 、 sodium methylate 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 三氟甲苯 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-[(2-Aminopyridin-4-Yl)methyl]-3-(2,4-Dioxo-1,2-Dihydrothieno[3,4-D]pyrimidin-3(4h)-Yl)-5-(Trifluoromethyl)-1h-Indole-2-Carboxylic Acid
  参考文献：
  名称：

  I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles

  摘要：

  SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50) = 0.9 mu M, replicon EC(50) > 100 mu M) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50) = 0.032 mu M, replicon EC(50) = 1.4 mu M) and 7r (NS5B IC(50) = 0.017 mu M, replicon EC(50) = 0.3 mu M) with improved enzyme and replicon activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.021
• 作为产物：
  描述：

  2-氰基-1-氟-4-(三氟甲基)苯 在 potassium tert-butylate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 1-benzyloxycarbonyl-3-isocyanato-5-trifIuoromethylindole-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles

  摘要：

  SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50) = 0.9 mu M, replicon EC(50) > 100 mu M) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50) = 0.032 mu M, replicon EC(50) = 1.4 mu M) and 7r (NS5B IC(50) = 0.017 mu M, replicon EC(50) = 0.3 mu M) with improved enzyme and replicon activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.021

文献信息

• [EN] 3-HETEROCYCLIC SUBSTITUTED INDOLE DERIVATIVES AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS D'INDOLE À SUBSTITUTION HÉTÉROCYCLIQUE EN POSITION 3 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SCHERING CORP

  公开号：WO2009064848A1

  公开（公告）日：2009-05-22

  The present invention relates to 3-Heterocyclic Substituted Indole Derivatives, compositions comprising at least one 3-Heterocyclic Substituted Indole Derivative, and methods of using the 3-Heterocyclic Substituted Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.

  本发明涉及3-杂环取代吲哚衍生物，包括至少一种3-杂环取代吲哚衍生物的组合物，以及使用3-杂环取代吲哚衍生物治疗或预防患者的病毒感染或与病毒相关的疾病的方法。
• 3-HETEROCYCLIC SUBSTITUTED INDOLE DERIVATIVES AND METHODS OF USE THEREOF
  申请人：Chan Tin-Yau

  公开号：US20110165118A1

  公开（公告）日：2011-07-07

  The present invention relates to 3-Heterocyclic Substituted Indole Derivatives, compositions comprising at least one 3-Heterocyclic Substituted Indole Derivative, and methods of using the 3-Heterocyclic Substituted Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.

  本发明涉及3-杂环取代吲哚衍生物，包括至少一种3-杂环取代吲哚衍生物的组合物，以及使用3-杂环取代吲哚衍生物治疗或预防患者的病毒感染或病毒相关疾病的方法。
• 3-heterocyclic substituted indole derivatives and methods of use thereof
  申请人：Chan Tin-Yau

  公开号：US08765757B2

  公开（公告）日：2014-07-01

  The present invention relates to 3-Heterocyclic Substituted Indole Derivatives, compositions comprising at least one 3-Heterocyclic Substituted Indole Derivative, and methods of using the 3-Heterocyclic Substituted Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.

  本发明涉及3-杂环取代吲哚衍生物、包含至少一种3-杂环取代吲哚衍生物的组合物以及使用3-杂环取代吲哚衍生物治疗或预防患者病毒感染或病毒相关疾病的方法。
• US8765757B2
  申请人：——

  公开号：US8765757B2

  公开（公告）日：2014-07-01
• I. Novel HCV NS5B polymerase inhibitors: Discovery of indole 2-carboxylic acids with C3-heterocycles
  作者：Gopinadhan N. Anilkumar、Charles A. Lesburg、Oleg Selyutin、Stuart B. Rosenblum、Qingbei Zeng、Yueheng Jiang、Tin-Yau Chan、Haiyan Pu、Henry Vaccaro、Li Wang、Frank Bennett、Kevin X. Chen、Jose Duca、Stephen Gavalas、Yuhua Huang、Patrick Pinto、Mousumi Sannigrahi、Francisco Velazquez、Srikanth Venkatraman、Bancha Vibulbhan、Sony Agrawal、Nancy Butkiewicz、Boris Feld、Eric Ferrari、Zhiqing He、Chuan-kui Jiang、Robert E. Palermo、Patricia Mcmonagle、H.-C. Huang、Neng-Yang Shih、George Njoroge、Joseph A. Kozlowski

  DOI：10.1016/j.bmcl.2011.07.021

  日期：2011.9

  SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50) = 0.9 mu M, replicon EC(50) > 100 mu M) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50) = 0.032 mu M, replicon EC(50) = 1.4 mu M) and 7r (NS5B IC(50) = 0.017 mu M, replicon EC(50) = 0.3 mu M) with improved enzyme and replicon activity. (C) 2011 Elsevier Ltd. All rights reserved.