(S)-methyl 4-chloromethyl-8-hydroxy-2-trifluoromethyl-6-<5-<(5,6,7-trimethoxyisoquinolin-3-ylcarbonyl)amino>-1H-indol-2-ylcarbonyl>-1,4,5,6-tetrahydropyrrolo<3,2-e>indole-3-carboxylate | 157904-30-8

• 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: (S)-methyl 4-chloromethyl-8-hydroxy-2-trifluoromethyl-6-<5-<(5,6,7-trimethoxyisoquinolin-3-ylcarbonyl)amino>-1H-indol-2-ylcarbonyl>-1,4,5,6-tetrahydropyrrolo<3,2-e>indole-3-carboxylate
• 英文别名: Methyl(1S)-1-chloromethyl-5-hydroxy-7-trifluoromethyl-3-[5-[(5,6,7-trimethoxyisoquinolin-3-ylcarbonyl)amino]-1H-indol-2-ylcarbonyl]-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-8-carboxylate；methyl (8S)-8-(chloromethyl)-4-hydroxy-2-(trifluoromethyl)-6-[5-[(5,6,7-trimethoxyisoquinoline-3-carbonyl)amino]-1H-indole-2-carbonyl]-7,8-dihydro-3H-pyrrolo[3,2-e]indole-1-carboxylate
• CAS: 157904-30-8
• 化学式: C₃₆H₂₉ClF₃N₅O₈
• 分子量: 752.103
• InChiKey: VHFJNSYEGIFRGI-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  53
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (S)-methyl 4-chloromethyl-8-hydroxy-2-trifluoromethyl-6-<5-<(5,6,7-trimethoxyisoquinolin-3-ylcarbonyl)amino>-1H-indol-2-ylcarbonyl>-1,4,5,6-tetrahydropyrrolo<3,2-e>indole-3-carboxylate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.83h， 生成 methyl (8S)-8-(chloromethyl)-4-(4-methylpiperazine-1-carbonyl)oxy-2-(trifluoromethyl)-6-[5-[(5,6,7-trimethoxyisoquinoline-3-carbonyl)amino]-1H-indole-2-carbonyl]-7,8-dihydro-3H-pyrrolo[3,2-e]indole-1-carboxylate
  参考文献：
  名称：

  Novel Cyclopropapyrroloindole Derivative (AT-3510) Bearing Methoxycarbonyl and Trifluoromethyl Groups

  摘要：

  The seco-Cl 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) derivatives dl- and/or (S)-10 carrying various acyl moieties at the NG-position were synthesized along with their prodrugs (S)-12, and their antitumor activity was evaluated. Among these derivatives, AT-3510 [(S)-12m], the novel prodrug MCTFCPI derivative carrying a 5-(7-methoxybenzofuran-2-ylcarbonyl)aminoindole-2-carbonyl group at the NG-position, was found to exhibit more excellent antitumor activity against human tumor xenografts than the clinical trial candidates carzelesin (6) and KW-2189 (7) and cisplatin.

  DOI：

  10.1021/jm980668c
• 作为产物：
  描述：

  2,3,4-三甲氧基-6-甲基苯甲醛 在 甲醇 、 氢氧化钾 、 乙醇 、 sodium 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 36.5h， 生成 (S)-methyl 4-chloromethyl-8-hydroxy-2-trifluoromethyl-6-<5-<(5,6,7-trimethoxyisoquinolin-3-ylcarbonyl)amino>-1H-indol-2-ylcarbonyl>-1,4,5,6-tetrahydropyrrolo<3,2-e>indole-3-carboxylate
  参考文献：
  名称：

  Novel Cyclopropapyrroloindole Derivative (AT-3510) Bearing Methoxycarbonyl and Trifluoromethyl Groups

  摘要：

  The seco-Cl 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) derivatives dl- and/or (S)-10 carrying various acyl moieties at the NG-position were synthesized along with their prodrugs (S)-12, and their antitumor activity was evaluated. Among these derivatives, AT-3510 [(S)-12m], the novel prodrug MCTFCPI derivative carrying a 5-(7-methoxybenzofuran-2-ylcarbonyl)aminoindole-2-carbonyl group at the NG-position, was found to exhibit more excellent antitumor activity against human tumor xenografts than the clinical trial candidates carzelesin (6) and KW-2189 (7) and cisplatin.

  DOI：

  10.1021/jm980668c

文献信息

• Trifluoromethylpyrroloindolecarboxylic acid ester and process for
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：US05629430A1

  公开（公告）日：1997-05-13

  Trifluoromethylpyrroloindolecarboxylic acid ester derivatives, and optical isomers and pharmaceutically acceptable salts thereof are provided which are represented by the general formula (1): ##STR1## or the general formula (2): ##STR2## The compounds are antineoplastic agents which are selective to cancer cells, effective also to solid cancer, and less toxic.

  提供了三氟甲基吡咯吲哌酮酸酯衍生物，以及它们的光学异构体和药学上可接受的盐，其通式表示为（1）： ##STR1## 或通式（2）： ##STR2## 这些化合物是选择性作用于癌细胞的抗肿瘤剂，对实体癌也有效，并且毒性较小。
• US5629430A
  申请人：——

  公开号：US5629430A

  公开（公告）日：1997-05-13
• Novel Cyclopropapyrroloindole Derivative (AT-3510) Bearing Methoxycarbonyl and Trifluoromethyl Groups
  作者：Yasumichi Fukuda、Hirosuke Furuta、Yoshie Kusama、Hiroyuki Ebisu、Yasuo Oomori、Shiro Terashima

  DOI：10.1021/jm980668c

  日期：1999.4.22

  The seco-Cl 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) derivatives dl- and/or (S)-10 carrying various acyl moieties at the NG-position were synthesized along with their prodrugs (S)-12, and their antitumor activity was evaluated. Among these derivatives, AT-3510 [(S)-12m], the novel prodrug MCTFCPI derivative carrying a 5-(7-methoxybenzofuran-2-ylcarbonyl)aminoindole-2-carbonyl group at the NG-position, was found to exhibit more excellent antitumor activity against human tumor xenografts than the clinical trial candidates carzelesin (6) and KW-2189 (7) and cisplatin.