(S)-6,7-二氢-1,2,3,10-四甲氧基-7-(苯甲酰基氨基)苯并[a]庚搭烯-9(5H)-酮 | 63989-75-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (S)-6,7-二氢-1,2,3,10-四甲氧基-7-(苯甲酰基氨基)苯并[a]庚搭烯-9(5H)-酮
• 英文名称: N-{(7S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl}benzamide
• 英文别名: N-benzoyl-N-deacetylcolchicine；N-((S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-benzamide；N-((S)-1,2,3,10-Tetramethoxy-9-oxo-5,6,7,9-tetrahydro-benzo[a]heptalen-7-yl)-benzamid；(S)-7-Benzoylamino-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-on；Benzamide, N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(a)heptalen-7-yl)-, (S)-；N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]benzamide
• CAS: 63989-75-3
• 化学式: C₂₇H₂₇NO₆
• 分子量: 461.514
• InChiKey: XTSSXTWGEJTWBM-FQEVSTJZSA-N

物化性质

• 沸点：
  566.01°C (rough estimate)
• 密度：
  1.2541 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 储存条件：
  应将商品存放在通风、低温、干燥的地方，并与其他库房内的食品原料分开存放。

制备方法与用途

类别：有毒物品
毒性分级：剧毒
急性毒性：腹腔-小鼠 LD50: 32 毫克/公斤；皮下-猫 LDL0: 12.5 毫克/公斤
可燃性危险特性：可燃，燃烧时会产生有毒的氮氧化物烟雾
储运特性：通风、低温、干燥，并与库房食品原料分开存放
灭火剂：干粉、泡沫、沙土、二氧化碳、雾状水

反应信息

• 作为反应物：
  描述：

  (S)-6,7-二氢-1,2,3,10-四甲氧基-7-(苯甲酰基氨基)苯并[a]庚搭烯-9(5H)-酮 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 10.0h， 生成 N-benzoyldeacetylcolchiceine
  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 、 苯甲酸酐 在 吡啶 作用下， 以 苯 为溶剂， 反应 8.0h， 生成 (S)-6,7-二氢-1,2,3,10-四甲氧基-7-(苯甲酰基氨基)苯并[a]庚搭烯-9(5H)-酮
  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

文献信息

• Effects on tubulin polymerization and down-regulation of c-Myc, hTERT and VEGF genes by colchicine haloacetyl and haloaroyl derivatives
  作者：Ana Marzo-Mas、Eva Falomir、Juan Murga、Miguel Carda、J. Alberto Marco

  DOI：10.1016/j.ejmech.2018.03.019

  日期：2018.4

  higher potency than colchicine itself. Some of the compounds, particularly the haloacetyl derivatives, inhibit the polymerization of tubulin in a similar manner as colchicine. As regards the cell cycle, the most active compounds are the chlorobenzoyl and bromobenzoyl derivatives, which cause cell cycle arrest at the G2/M phase when tested at 20 nM, and the bromoacetyl derivative, which arrests the cell

  几种秋水仙碱类似物，其中N-乙酰基残基已被卤代乙酰基，环己基乙酰基，苯乙酰基取代，并且已经合成了各种芳酰基部分。已在三种肿瘤细胞系（HT-29，MCF-7和A549）和一种非肿瘤细胞系（HEK-293）上测量了合成化合物的细胞毒活性。这些化合物在纳摩尔水平上显示出很高的抗增殖活性，在许多情况下具有比秋水仙碱本身更高的效力。一些化合物，特别是卤代乙酰基衍生物，以类似于秋水仙碱的方式抑制微管蛋白的聚合。关于细胞周期，最具活性的化合物是氯苯甲酰基和溴苯甲酰基衍生物，当在20 nM下进行测试时，它们会在G2 / M期导致细胞周期停滞；而溴乙酰基衍生物则在15 nM下导致细胞周期停滞。此外，浓度很低的Myc，hTERT和VEGF基因以及VEGF蛋白的分泌。
• Santavy, Chemicke Listy, 1952, vol. 46, p. 280,284
  作者：Santavy

  DOI：——

  日期：——
• 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.