methyl (1R,12S)-10-[(E)-3-(6-methoxypyridin-3-yl)prop-2-enoyl]-4-methyl-7-oxo-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-3-carboxylate | 221549-87-7

• 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: methyl (1R,12S)-10-[(E)-3-(6-methoxypyridin-3-yl)prop-2-enoyl]-4-methyl-7-oxo-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-3-carboxylate
• CAS: 221549-87-7
• 化学式: C₂₃H₂₁N₃O₅
• 分子量: 419.437
• InChiKey: GZKPFBIMMOZJJC-GPWVTEAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (1R,12S)-10-[(E)-3-(6-methoxypyridin-3-yl)prop-2-enoyl]-4-methyl-7-oxo-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-3-carboxylate 在 氢溴酸 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 (S)-8-Bromomethyl-4-hydroxy-6-[(E)-3-(6-methoxy-pyridin-3-yl)-acryloyl]-2-methyl-3,6,7,8-tetrahydro-pyrrolo[3,2-e]indole-1-carboxylic acid methyl ester
  参考文献：
  名称：

  New Water-Soluble Duocarmycin Derivatives: Synthesis and Antitumor Activity of A-Ring Pyrrole Compounds Bearing β-Heteroarylacryloyl Groups

  摘要：

  A series of A-ring pyrrole compounds of duocarmycin bearing 4'-methoxy-beta-heteroarylacryloyl groups were synthesized and evaluated for in vitro anticellular activity against HeLa S-3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. Most of the Li 4'-methoxy-beta-heteroarylacrylates displayed in vitro anticellular activity equivalent to that of 4'-methoxycinnamates, Among the 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates, compound 15b having a (4-methoxy-3,5-pyrimidinyl)acryloyl as segment-B (Seg-B) showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in Seg-B, which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates. Moreover, these 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates had high aqueous solubility.

  DOI：

  10.1021/jm980559y
• 作为产物：
  描述：

  (2E)-3-[6-methoxy(pyridin-3-yl)]prop-2-enoic acid 在 sodium hydride 、 1-methyl-2-chloropyridinium chloride 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.67h， 生成 methyl (1R,12S)-10-[(E)-3-(6-methoxypyridin-3-yl)prop-2-enoyl]-4-methyl-7-oxo-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),3,8-triene-3-carboxylate
  参考文献：
  名称：

  New Water-Soluble Duocarmycin Derivatives: Synthesis and Antitumor Activity of A-Ring Pyrrole Compounds Bearing β-Heteroarylacryloyl Groups

  摘要：

  A series of A-ring pyrrole compounds of duocarmycin bearing 4'-methoxy-beta-heteroarylacryloyl groups were synthesized and evaluated for in vitro anticellular activity against HeLa S-3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. Most of the Li 4'-methoxy-beta-heteroarylacrylates displayed in vitro anticellular activity equivalent to that of 4'-methoxycinnamates, Among the 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates, compound 15b having a (4-methoxy-3,5-pyrimidinyl)acryloyl as segment-B (Seg-B) showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in Seg-B, which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates. Moreover, these 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates had high aqueous solubility.

  DOI：

  10.1021/jm980559y

文献信息

• New Water-Soluble Duocarmycin Derivatives: Synthesis and Antitumor Activity of A-Ring Pyrrole Compounds Bearing β-Heteroarylacryloyl Groups
  作者：Nobuyoshi Amishiro、Satoru Nagamura、Eiji Kobayashi、Katsushige Gomi、Hiromitsu Saito

  DOI：10.1021/jm980559y

  日期：1999.2.1

  A series of A-ring pyrrole compounds of duocarmycin bearing 4'-methoxy-beta-heteroarylacryloyl groups were synthesized and evaluated for in vitro anticellular activity against HeLa S-3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. Most of the Li 4'-methoxy-beta-heteroarylacrylates displayed in vitro anticellular activity equivalent to that of 4'-methoxycinnamates, Among the 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates, compound 15b having a (4-methoxy-3,5-pyrimidinyl)acryloyl as segment-B (Seg-B) showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in Seg-B, which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates. Moreover, these 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates had high aqueous solubility.