6-Amino-1[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-chloromethylindoline

• 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: 6-Amino-1[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-chloromethylindoline
• 英文别名: N-[5-[(E)-3-[6-amino-3-(chloromethyl)-2,3-dihydroindol-1-yl]-3-oxoprop-1-enyl]-1-methylpyrrol-3-yl]butanamide
• 化学式: C₂₁H₂₅ClN₄O₂
• 分子量: 400.908
• InChiKey: ZEHUETDVFMNOCM-SOFGYWHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  氯甲酸对硝基苄酯 、 6-Amino-1[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-chloromethylindoline 、 水 在 水 、 乙酸乙酯 作用下， 以 吡啶 为溶剂， 反应 2.0h， 以to give 1-[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-(chloromethyl)-6-[(4-nitrobenzyloxy)carbonyl]aminoindoline (8a) (49 mg, 71%) as a yellow solid, mp 207-209.5° C的产率得到1-[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-(chloromethyl)-6-[(4-nitrobenzyloxy)carbonyl]aminoindoline
  参考文献：
  名称：

  Seco precursors of cyclopropylindolines and their use as prodrugs

  摘要：

  一种化合物，为式(I)的6-取代seco吲哚，其中：X代表卤素或OSO2R，其中R表示H或C1-5烷基，可选地取代1-4个羟基、酸（COOH）或氨基，该氨基可以可选地被1-2个C1-5烷基取代；Y为N02、N3、NHOH、NHR、NRR、N═NR、N（O）RR、SR或SSR，其中R的定义如上所述，但在Y为SSR或N═NR的情况下，则R还可以是式(I)的另一个基团；或Y为式：（无法翻译，可能是公式）

  公开号：

  US06251933B1
• 作为产物：
  描述：

  1-(tert-butyloxycarbonyl)-3-chloromethyl-6-nitroindoline 在 盐酸 、 铁粉 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 21.25h， 生成 6-Amino-1[(E)-4-butyramido-1-methyl-2-pyrroleacryloyl]-3-chloromethylindoline
  参考文献：
  名称：

  Synthesis of 1-Substituted 3-(Chloromethyl)-6-aminoindoline (6-Amino-seco-CI) DNA Minor Groove Alkylating Agents and Structure−Activity Relationships for Their Cytotoxicity

  摘要：

  A series of racemic 6-amino-seco-cyclopropylindole (seco-CI) compounds was prepared by coupling 1-(tert-butyloxycarbonyl)-3-(chloromethyl)-6-nitroindoline with appropriate acids, followed by nitro group reduction, and evaluated for cytotoxicity in AA8, UV4, EMT6, and SKOV3 cell lines. These compounds are of interest due to their close structural relationship to known AT-specific alkylating agents and cytotoxins and also for the possible construction of stable amine-based prodrugs designed for tumor-specific release. Variations included indole or furan side chains with different substituents, sulfonamide or carboxamide linkers, extension of the minor groove binding side chain to two subunits, and the use of a pyrroylacryloyl unit previously reported to give extremely potent analogues. The parent compound, with a trimethoxyindole side chain, was a moderately potent cytotoxin (IC50 = 0.34 mu M in AA8 cells, 4 h exposure). A single 5-methoxy group on the indole minor groove binding unit was sufficient to maintain potency, and a series of dimethylaminoethoxy-substituted analogues retained the cytotoxicity of the parent compound, while providing increased aqueous solubility.

  DOI：

  10.1021/jm980545s

文献信息

• Synthesis of 1-Substituted 3-(Chloromethyl)-6-aminoindoline (6-Amino-<i>seco</i>-CI) DNA Minor Groove Alkylating Agents and Structure−Activity Relationships for Their Cytotoxicity
  作者：Jared B. J. Milbank、Moana Tercel、Graham J. Atwell、William R. Wilson、Alison Hogg、William A. Denny

  DOI：10.1021/jm980545s

  日期：1999.2.1

  A series of racemic 6-amino-seco-cyclopropylindole (seco-CI) compounds was prepared by coupling 1-(tert-butyloxycarbonyl)-3-(chloromethyl)-6-nitroindoline with appropriate acids, followed by nitro group reduction, and evaluated for cytotoxicity in AA8, UV4, EMT6, and SKOV3 cell lines. These compounds are of interest due to their close structural relationship to known AT-specific alkylating agents and cytotoxins and also for the possible construction of stable amine-based prodrugs designed for tumor-specific release. Variations included indole or furan side chains with different substituents, sulfonamide or carboxamide linkers, extension of the minor groove binding side chain to two subunits, and the use of a pyrroylacryloyl unit previously reported to give extremely potent analogues. The parent compound, with a trimethoxyindole side chain, was a moderately potent cytotoxin (IC50 = 0.34 mu M in AA8 cells, 4 h exposure). A single 5-methoxy group on the indole minor groove binding unit was sufficient to maintain potency, and a series of dimethylaminoethoxy-substituted analogues retained the cytotoxicity of the parent compound, while providing increased aqueous solubility.
• Seco precursors of cyclopropylindolines and their use as prodrugs
  申请人：The Cancer Research Campaign Technology Limited

  公开号：US06251933B1

  公开（公告）日：2001-06-26

  A compound which is a 6-substituted seco indoline of the formula (I): wherein: X is halogen or OSO2R where R represents H or C1-5 alkyl optionally substituted with from 1 to 4 hydroxyl, acid (COOH) or amino groups which amino may be optionally substituted by one or two C1-5 alkyl groups; Y is N02, N3, NHOH, NHR, NRR, N═NR, N(O)RR, SR or SSR, where R is defined as above, but that in the case where Y is SSR or N═NR, then R can also be another moiety of formula (I); or Y is a group of formula:

  一种化合物，为式(I)的6-取代seco吲哚，其中：X代表卤素或OSO2R，其中R表示H或C1-5烷基，可选地取代1-4个羟基、酸（COOH）或氨基，该氨基可以可选地被1-2个C1-5烷基取代；Y为N02、N3、NHOH、NHR、NRR、N═NR、N（O）RR、SR或SSR，其中R的定义如上所述，但在Y为SSR或N═NR的情况下，则R还可以是式(I)的另一个基团；或Y为式：（无法翻译，可能是公式）