methyl (1R,12S)-10-[(E)-3-(3-amino-4-methoxyphenyl)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 | 186760-18-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl (1R,12S)-10-[(E)-3-(3-amino-4-methoxyphenyl)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: 186760-18-9
• 化学式: C₂₄H₂₃N₃O₅
• 分子量: 433.464
• InChiKey: CQIZTTJFRDPUPT-MTZNPKDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (1R,12S)-10-[(E)-3-(3-amino-4-methoxyphenyl)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 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.5h， 生成 methyl (8S)-6-[(E)-3-(3-amino-4-methoxyphenyl)prop-2-enoyl]-8-(bromomethyl)-2-methyl-4-(4-methylpiperazine-1-carbonyl)oxy-7,8-dihydro-3H-pyrrolo[3,2-e]indole-1-carboxylate
  参考文献：
  名称：

  Synthesis and Antitumor Activity of Duocarmycin Derivatives:  A-Ring Pyrrole Compounds Bearing Cinnamoyl Groups

  摘要：

  A series of N-cinnamates of the A-ring pyrrole compound of duocarmycin 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. The 4'-methoxy- and 4'-BocNH-cinnamates exhibited strong in vitro anticellular activity among the synthesized compounds. The ortho substitution of the 4'-methoxycinnamate did not affect the anticellular activity and contributed to an enhancement of water solubility. Most of the 8-O-(N,N-dialkylcarbamoyl) derivatives of the 4'-methoxycinnamates displayed remarkably superior in vivo antitumor activity to duocarmycin A or B2. Moreover, it is noteworthy that these 8-O-(N,N-dialkylcarbamoyl) derivatives exhibited significant antitumor activity at wider range of doses as compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment B.

  DOI：

  10.1021/jm9606094
• 作为产物：
  描述：

  3-methoxycarbonyl-2-methylduocarmycin A 在 甲醇 、 氢溴酸 、 sodium methylate 、 sodium hydride 、 三乙胺 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 11.0h， 生成 methyl (1R,12S)-10-[(E)-3-(3-amino-4-methoxyphenyl)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：

  Synthesis and Antitumor Activity of Duocarmycin Derivatives:  A-Ring Pyrrole Compounds Bearing Cinnamoyl Groups

  摘要：

  A series of N-cinnamates of the A-ring pyrrole compound of duocarmycin 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. The 4'-methoxy- and 4'-BocNH-cinnamates exhibited strong in vitro anticellular activity among the synthesized compounds. The ortho substitution of the 4'-methoxycinnamate did not affect the anticellular activity and contributed to an enhancement of water solubility. Most of the 8-O-(N,N-dialkylcarbamoyl) derivatives of the 4'-methoxycinnamates displayed remarkably superior in vivo antitumor activity to duocarmycin A or B2. Moreover, it is noteworthy that these 8-O-(N,N-dialkylcarbamoyl) derivatives exhibited significant antitumor activity at wider range of doses as compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment B.

  DOI：

  10.1021/jm9606094

文献信息

• Synthesis and Antitumor Activity of Duocarmycin Derivatives:  A-Ring Pyrrole Compounds Bearing Cinnamoyl Groups
  作者：Satoru Nagamura、Akira Asai、Nobuyoshi Amishiro、Eiji Kobayashi、Katsushige Gomi、Hiromitsu Saito

  DOI：10.1021/jm9606094

  日期：1997.3.1

  A series of N-cinnamates of the A-ring pyrrole compound of duocarmycin 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. The 4'-methoxy- and 4'-BocNH-cinnamates exhibited strong in vitro anticellular activity among the synthesized compounds. The ortho substitution of the 4'-methoxycinnamate did not affect the anticellular activity and contributed to an enhancement of water solubility. Most of the 8-O-(N,N-dialkylcarbamoyl) derivatives of the 4'-methoxycinnamates displayed remarkably superior in vivo antitumor activity to duocarmycin A or B2. Moreover, it is noteworthy that these 8-O-(N,N-dialkylcarbamoyl) derivatives exhibited significant antitumor activity at wider range of doses as compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment B.