3-(tert-butyloxycarbonyl)-1-[(methanesulfonyloxy)methyl]-5-nitro-1,2-dihydro-3H-benz[e]indole | 204915-95-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(tert-butyloxycarbonyl)-1-[(methanesulfonyloxy)methyl]-5-nitro-1,2-dihydro-3H-benz[e]indole
• 英文别名: 3-(tert-butoxycarbonyl)-1-<(methanesulfonyloxy)methyl>-5-nitro-1,2-dihydro-3H-benzindole；tert-butyl 1-(methylsulfonyloxymethyl)-5-nitro-1,2-dihydrobenzo[e]indole-3-carboxylate
• CAS: 204915-95-7
• 化学式: C₁₉H₂₂N₂O₇S
• 分子量: 422.459
• InChiKey: OVXVUFRXNREXIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(tert-butyloxycarbonyl)-1-[(methanesulfonyloxy)methyl]-5-nitro-1,2-dihydro-3H-benz[e]indole 在 lithium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以87%的产率得到3-(tert-butyloxycarbonyl)-1-(chloromethyl)-5-nitro-1,2-dihydro-3H-benzindole
  参考文献：
  名称：

  Synthesis and Cytotoxicity of 5-Amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2- dihydro-3H-benz[e]indole (Amino-seco-CBI-TMI) and Related 5-Alkylamino Analogues:  New DNA Minor Groove Alkylating Agents

  摘要：

  The first synthesis of seco-CBI-TMI alkylating agents with 5-nitrogen substituents is reported. The parent 5-amino compound was prepared in a 15-step synthesis from 1-hydroxynaphthalene-2-carboxylic acid. Reductive alkylation of the 5-amino compound gave the corresponding 5-methylamino and 5-dimethylamino analogues, while resolution of an intermediate by chiral HPLC allowed preparation of the R and S enantiomers of the 5-amino analogue. Absolute configuration was assigned by X-ray crystallography. The S enantiomer was about 65-fold more cytotoxic than the R enantiomer in cell line assays. The 5-amino and 5-methylamino compounds had in vitro cytotoxicities comparable to that of the known 5-hydroxy analogue (0.2-0.5 nM), while the 5-dimethylamino derivative was about 10-fold less potent. The high potencies of the 5-amino and 5-methylamino analogues make them of interest for the formation of relatively stable amine-based prodrugs.

  DOI：

  10.1021/jo981395w
• 作为产物：
  描述：

  3-(tert-butoxycarbonyl)-1,1-di(methoxycarbonyl)-5-nitro-1,2-dihydro-3H-benzindole 在 sodium methylate 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 正己烷 为溶剂， 反应 3.0h， 生成 3-(tert-butyloxycarbonyl)-1-[(methanesulfonyloxy)methyl]-5-nitro-1,2-dihydro-3H-benz[e]indole
  参考文献：
  名称：

  Synthesis and Cytotoxicity of 5-Amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2- dihydro-3H-benz[e]indole (Amino-seco-CBI-TMI) and Related 5-Alkylamino Analogues:  New DNA Minor Groove Alkylating Agents

  摘要：

  The first synthesis of seco-CBI-TMI alkylating agents with 5-nitrogen substituents is reported. The parent 5-amino compound was prepared in a 15-step synthesis from 1-hydroxynaphthalene-2-carboxylic acid. Reductive alkylation of the 5-amino compound gave the corresponding 5-methylamino and 5-dimethylamino analogues, while resolution of an intermediate by chiral HPLC allowed preparation of the R and S enantiomers of the 5-amino analogue. Absolute configuration was assigned by X-ray crystallography. The S enantiomer was about 65-fold more cytotoxic than the R enantiomer in cell line assays. The 5-amino and 5-methylamino compounds had in vitro cytotoxicities comparable to that of the known 5-hydroxy analogue (0.2-0.5 nM), while the 5-dimethylamino derivative was about 10-fold less potent. The high potencies of the 5-amino and 5-methylamino analogues make them of interest for the formation of relatively stable amine-based prodrugs.

  DOI：

  10.1021/jo981395w

文献信息

• 5-Amino-1-(chloromethyl)-1,2-dihydro-3<i>H</i>-benz[<i>e</i>]indoles:  Relationships between Structure and Cytotoxicity for Analogues Bearing Different DNA Minor Groove Binding Subunits
  作者：Graham J. Atwell、Jared J. B. Milbank、William R. Wilson、Alison Hogg、William A. Denny

  DOI：10.1021/jm990136b

  日期：1999.8.1

  relationships for the cytotoxicity of side chain analogues. Compounds were prepared by coupling 1-(chloromethyl)-5-nitro-1, 2-dihydro-3H-benz[e]indole to appropriate carboxylic acids, followed by nitro group reduction, or by coupling suitable 5-amino-protected indolines to alpha,beta-unsaturated acids, followed by deblocking. These AT-specific DNA alkylating agents were evaluated for cytotoxicity in a series

  制备了一系列5-氨基-seco-CBI化合物，设计用作前药的效应子，以研究结构-活性关系对侧链类似物的细胞毒性。通过将1-（氯甲基）-5-硝基-1，2-二氢-3H-苯并[e]吲哚与合适的羧酸偶联，然后进行硝基还原，或通过将合适的5-氨基保护的二氢吲哚偶联至化合物来制备化合物。 α，β-不饱和酸，然后脱保护。在一系列肿瘤细胞系（AA8，UV4，EMT6，SKOV3）中评估了这些AT特异的DNA烷基化剂的细胞毒性。对于那些带有吲哚羰基侧链的类似物，5'-甲氧基衍生物具有最高的细胞毒性（AA8细胞中IC（50）1.3 nM，暴露4 h），与亲本CBI-TMI（5'，6' ，7'-三甲氧基吲哚）衍生物（IC（50）0。在上述测定中为46 nM）。带有O（CH（2））（2）NMe（2）取代基的增溶衍生物的子集的效力降低了约10倍。对于在侧链中含有丙烯酰基接头的化合物，证明4'-甲氧基肉桂酰基衍生物具
• Condensed N-aclyindoles as antitumor agents
  申请人：Cancer Research Campaign Technology Limited

  公开号：US06130237A1

  公开（公告）日：2000-10-10

  The invention provides compounds of general formula (I), wherein: X is halogen or OSO.sub.2 R, where R represents H or is unsubstituted or hydroxy-or amino-substituted lower alkyl; Y is a nitro or amine group or a substituted derivative thereof; W is selected from the structures of formulae (Ia, Ib or Ic), where E is --N.dbd. or --CH.dbd., G is O, S, or NH, and Q is either up to three of R, OR, NRR, NO.sub.2, CONHR, NHCOR or NHCONHR, or is an additional group of formulae (Ia, Ib or Ic) and HET represents a 5- or 6-membered carbocycle or heterocycle; and A and B collectively represent a fused benzene or 2-CO.sub.2 R pyrrole ring. In one embodiment, the group Y is an amine derivative substituted by a group which is a substrate for a nitroreductase or carboxypeptidase enzyme such that one of said enzymes is able to bring about removal of that group. ##STR1##

  本发明提供了一般式（I）的化合物，其中：X是卤素或OSO.sub.2 R，其中R代表H或未取代或羟基或氨基取代的低碳基；Y是硝基或胺基或其取代衍生物；W从式（Ia、Ib或Ic）的结构中选择，其中E是--N.dbd.或--CH.dbd.，G是O、S或NH，Q是R、OR、NRR、NO.sub.2、CONHR、NHCOR或NHCONHR中的最多三个，或是公式（Ia、Ib或Ic）的另外一个基团，HET代表一个5-或6-成员的碳环或杂环；A和B共同代表融合苯或2-CO.sub.2R吡咯环。在一个实施例中，群Y是胺衍生物，被一个硝基还原酶或羧肽酶酶的底物取代，以便其中一种酶能够去除该基团。##STR1##
• CYCLOPROPYLINDOLE COMPOUNDS AND THEIR USE AS PRODRUGS
  申请人：AUCKLAND UNISERVICES LIMITED

  公开号：EP0938474B1

  公开（公告）日：2005-11-23
• US6130237A
  申请人：——

  公开号：US6130237A

  公开（公告）日：2000-10-10
• Synthesis and Cytotoxicity of 5-Amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2- dihydro-3<i>H</i>-benz[<i>e</i>]indole (Amino-<i>s</i><i>eco</i>-CBI-TMI) and Related 5-Alkylamino Analogues:  New DNA Minor Groove Alkylating Agents
  作者：Graham J. Atwell、Moana Tercel、Maruta Boyd、William R. Wilson、William A. Denny

  DOI：10.1021/jo981395w

  日期：1998.12.1

  The first synthesis of seco-CBI-TMI alkylating agents with 5-nitrogen substituents is reported. The parent 5-amino compound was prepared in a 15-step synthesis from 1-hydroxynaphthalene-2-carboxylic acid. Reductive alkylation of the 5-amino compound gave the corresponding 5-methylamino and 5-dimethylamino analogues, while resolution of an intermediate by chiral HPLC allowed preparation of the R and S enantiomers of the 5-amino analogue. Absolute configuration was assigned by X-ray crystallography. The S enantiomer was about 65-fold more cytotoxic than the R enantiomer in cell line assays. The 5-amino and 5-methylamino compounds had in vitro cytotoxicities comparable to that of the known 5-hydroxy analogue (0.2-0.5 nM), while the 5-dimethylamino derivative was about 10-fold less potent. The high potencies of the 5-amino and 5-methylamino analogues make them of interest for the formation of relatively stable amine-based prodrugs.