乙基[(7S)-1,2,3,10-四甲氧基-9-氧代-5,6,7,9-四氢苯并[a]庚搭烯-7-基]氨基甲酸酯 | 86436-42-2

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 中文名称: 乙基[(7S)-1,2,3,10-四甲氧基-9-氧代-5,6,7,9-四氢苯并[a]庚搭烯-7-基]氨基甲酸酯
• 英文名称: N-(ethoxycarbonyl)-deacetylcolchicine
• 英文别名: N-(ethoxycarbonyl)deacetylcolchicine；N-ethoxycarbonyldeacetylcolchicine；Benzo(a)heptalene-7-carbamic acid, 5,6,7,9-tetrahydro-9-oxo-1,2,3,10-tetramethoxy-, ethyl ester, (S)-；ethyl N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]carbamate
• CAS: 86436-42-2
• 化学式: C₂₃H₂₇NO₇
• 分子量: 429.47
• InChiKey: NLHICQCHEWUHCR-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  92.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  乙基[(7S)-1,2,3,10-四甲氧基-9-氧代-5,6,7,9-四氢苯并[a]庚搭烯-7-基]氨基甲酸酯 、 N-carbethoxydeacetylisocolchicine 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 10.0h， 生成 N-carbethoxydeacetylcolchiceine
  参考文献：
  名称：

  Biological effects of modified colchicines. 2. Evaluation of catecholic colchicines, colchifolines, colchicide, and novel N-acyl- and N-aroyldeacetylcolchicines

  摘要：

  A series of natural and synthetic colchicine derivatives was examined for their potency in the lymphocytic leukemia P388 screen in mice, for their toxicity in mice, and for their binding to microtubule protein. The natural alkaloids cornigerine and colchifoline and several N,O-substituted analogues of colchifoline were found to be as potent and as toxic as colchicine in the P388 screen with good affinity for tubulin. The 1,2-(methylenedioxy)-substituted isomer of cornigerine was considerably less potent in vivo than could have been anticipated from the in vitro tubulin binding data. Several N-acyl and N-aroyl derivatives prepared from deacetylcolchicine showed high potency in the in vitro and in vivo screens. Colchicide was found to be highly potent in vivo, and N-carbethoxydeacetylcolchicine, a synthetic analogue of colchicine with a N-carbethoxy instead of an N-acetyl function, showed interesting biological properties.

  DOI：

  10.1021/jm00364a006
• 作为产物：
  描述：

  (7S)-7-氨基-1,2,3,10-四甲氧基-6,7-二氢-5H-苯并[g]庚搭烯-9-酮 、 氯甲酸乙酯 在 吡啶 作用下， 生成 乙基[(7S)-1,2,3,10-四甲氧基-9-氧代-5,6,7,9-四氢苯并[a]庚搭烯-7-基]氨基甲酸酯
  参考文献：
  名称：

  Antitubulin effects of derivatives of 3-demethylthiocolchicine, methylthio ethers of natural colchicinoids, and thioketones derived from thiocolchicine. Comparison with colchicinoids

  摘要：

  Esterification of the phenolic group in 3-demethylthiocolchicine and exchange of the N-acetyl group with other N-acyl groups or a N-carbalkoxy group afforded many compounds which showed superior activity over the parent drug as inhibitors of tubulin polymerization and of the growth of L1210 murine leukemia cells in culture. A comparison of naturally occurring Colchicum alkaloids with thio isosters, obtained by replacing the OMe group at C(10) with a SCH3 group, showed the thio ethers to be invariably more potent in these assays. The comparison included 3-demethylthiodemecolcine prepared from 3-demethylthiocolchicine by partial synthesis. Thiation of thiocolchicine with Lawesson's reagent afforded novel thiotropolones which exhibited high antitubulin activity. Their structures are fully secured by spectral data. Colchicine and several of its analogues show good antitumor effect in mice infected with P388 lymphocytic leukemia, and all of them show high affinity for tubulin and inhibit tubulin polymerization at low concentration. Consequently, antitubulin assays with this class of compounds can serve as valuable prescreens for the initial evaluation of potential antitumor drugs.

  DOI：

  10.1021/jm00164a015

文献信息

• BROSSI, A.;KEREKES, P.
  作者：BROSSI, A.、KEREKES, P.

  DOI：——

  日期：——
• Antitubulin effects of derivatives of 3-demethylthiocolchicine, methylthio ethers of natural colchicinoids, and thioketones derived from thiocolchicine. Comparison with colchicinoids
  作者：Anjum Muzaffar、Arnold Brossi、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00164a015

  日期：1990.2

  Esterification of the phenolic group in 3-demethylthiocolchicine and exchange of the N-acetyl group with other N-acyl groups or a N-carbalkoxy group afforded many compounds which showed superior activity over the parent drug as inhibitors of tubulin polymerization and of the growth of L1210 murine leukemia cells in culture. A comparison of naturally occurring Colchicum alkaloids with thio isosters, obtained by replacing the OMe group at C(10) with a SCH3 group, showed the thio ethers to be invariably more potent in these assays. The comparison included 3-demethylthiodemecolcine prepared from 3-demethylthiocolchicine by partial synthesis. Thiation of thiocolchicine with Lawesson's reagent afforded novel thiotropolones which exhibited high antitubulin activity. Their structures are fully secured by spectral data. Colchicine and several of its analogues show good antitumor effect in mice infected with P388 lymphocytic leukemia, and all of them show high affinity for tubulin and inhibit tubulin polymerization at low concentration. Consequently, antitubulin assays with this class of compounds can serve as valuable prescreens for the initial evaluation of potential antitumor drugs.
• Biological effects of modified colchicines. 2. Evaluation of catecholic colchicines, colchifolines, colchicide, and novel N-acyl- and N-aroyldeacetylcolchicines
  作者：Arnold Brossi、Padam N. Sharma、Louise Atwell、Arthur E. Jacobson、Maria A. Iorio、Marisa Molinari、Colin F. Chignell

  DOI：10.1021/jm00364a006

  日期：1983.10

  A series of natural and synthetic colchicine derivatives was examined for their potency in the lymphocytic leukemia P388 screen in mice, for their toxicity in mice, and for their binding to microtubule protein. The natural alkaloids cornigerine and colchifoline and several N,O-substituted analogues of colchifoline were found to be as potent and as toxic as colchicine in the P388 screen with good affinity for tubulin. The 1,2-(methylenedioxy)-substituted isomer of cornigerine was considerably less potent in vivo than could have been anticipated from the in vitro tubulin binding data. Several N-acyl and N-aroyl derivatives prepared from deacetylcolchicine showed high potency in the in vitro and in vivo screens. Colchicide was found to be highly potent in vivo, and N-carbethoxydeacetylcolchicine, a synthetic analogue of colchicine with a N-carbethoxy instead of an N-acetyl function, showed interesting biological properties.