methyl (E)-4-butyramido-1-methyl-2-pyrroleacrylate | 204915-82-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: methyl (E)-4-butyramido-1-methyl-2-pyrroleacrylate
• 英文别名: methyl (E)-4-butyrylamino-1-methyl-2-pyrroleacrylate；(E)-methyl 4-butyramido-1-methyl-2-pyrroleacrylate；methyl (E)-3-[4-(butanoylamino)-1-methylpyrrol-2-yl]prop-2-enoate
• CAS: 204915-82-2
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: CCZSKIJGGMGMML-VOTSOKGWSA-N

物化性质

• 熔点：
  109-110 °C
• 沸点：
  457.8±35.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (E)-4-butyramido-1-methyl-2-pyrroleacrylate 在 sodium hydroxide 、 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 甲醇 、 水 为溶剂， 反应 21.08h， 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
• 作为产物：
  描述：

  1-甲基-4-硝基吡咯-2-甲醛 在 铁粉 作用下， 以 甲醇 、 水 、 苯 为溶剂， 反应 25.25h， 生成 methyl (E)-4-butyramido-1-methyl-2-pyrroleacrylate
  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

• 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-取代的内吲哚，其中： X为卤素或OSO2R，其中R代表H或C1-5烷基，可选地取代为1至4个羟基、酸（COOH）或氨基，该氨基可选地被一个或两个C1-5烷基取代； Y为N02、N3、NHOH、NHR、NRR、N═NR、N(O)RR、SR或SSR，其中R如上定义，但在Y为SSR或N═NR的情况下，R也可以是式(I)的另一个基团； 或Y为以下式的基团：
• SECO PRECURSORS OF CYCLOPROPYLINDOLINES AND THEIR USE AS PRODRUGS
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED

  公开号：EP0944596A1

  公开（公告）日：1999-09-29
• US6251933B1
  申请人：——

  公开号：US6251933B1

  公开（公告）日：2001-06-26
• [EN] SECO PRECURSORS OF CYCLOPROPYLINDOLINES AND THEIR USE AS PRODRUGS<br/>[FR] PRECURSEURS SECO DE CYCLOPROPYLINDOLINES ET LEUR UTILISATION EN TANT QUE PROMEDICAMENTS
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED

  公开号：WO1998025898A1

  公开（公告）日：1998-06-18

  (EN) The present invention relates to novel amino analogues of the general class of cyclopropylindoles and their seco precursors, and is particularly concerned with the use of these compounds as prodrugs for antibody-directed enzyme-prodrug therapy (ADEPT) and gene-directed enzyme-prodrug therapy (GDEPT) for cancer.(FR) La présente invention concerne de nouveaux analogues amino de la classe générale des cyclopropylindoles et des précurseurs seco de ceux-ci, et elle concerne notamment l'utilisation de ces composés en tant que promédicaments destinés à une thérapie du cancer par administration d'un de ces promédicaments et d'un conjugué anticorps-enzyme (ADEPT), ou par administration d'un de ces promédicaments et d'un conjugué anticorps-gène (GDEPT).
• 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.