(S)-2,2,2-三氟-N-(5,6,7,9-四氢-2-羟基-1,3,10-三甲氧基-9-氧代苯并[a]庚搭烯-7-基)-乙酰胺 | 86436-46-6

• 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: (S)-2,2,2-三氟-N-(5,6,7,9-四氢-2-羟基-1,3,10-三甲氧基-9-氧代苯并[a]庚搭烯-7-基)-乙酰胺
• 英文名称: 2-demethyl-N-(trifluoroacetyl)deacetylcolchicine
• 英文别名: 2-Demethyl-N-trifluoroacetyl-deacetylcolchicine；2,2,2-trifluoro-N-[(7S)-2-hydroxy-1,3,10-trimethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 86436-46-6
• 化学式: C₂₁H₂₀F₃NO₆
• 分子量: 439.388
• InChiKey: BXGLTIXFXLUVOH-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  94.1
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-[(S)-5,6,7,9-四氢-1,2,3,10-四甲氧基-9-氧代苯并[a]庚搭烯-7-基]-2,2,2-三氟乙酰胺 在 硫酸 作用下， 反应 3.0h， 以24%的产率得到(S)-2,2,2-三氟-N-(5,6,7,9-四氢-2-羟基-1,3,10-三甲氧基-9-氧代苯并[a]庚搭烯-7-基)-乙酰胺
  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

• 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.
• Fluorinated colchicinoids: antitubulin and cytotoxic properties
  作者：Israel Ringel、Dena Jaffe、Sara Alerhand、Oliver Boye、Anjum Muzaffar、Arnold Brossi

  DOI：10.1021/jm00115a026

  日期：1991.11

  The synthesis of B-ring and C-ring trifluoroacetamide-substituted colchicinoids and fluoro-substituted colchicineethylamides is presented. The B-ring trifluoroacetamido-substituted analogues exhibit moderate enhancement of potency compared to the nonfluorinated analogues for tubulin assembly inhibition and cytotoxicity toward two wild type cell lines. The C-ring substituted fluoroethylamides have reduced relative potencies in the same systems due to the strong electron-withdrawing effect of the fluoro derivatives. The fluoro colchicinoids are much more cytotoxic toward drug-resistant cell lines than to the wild type cell lines. Their enhanced potency is probably due to an effect of the fluoro moiety on functions specific to resistant cells and/or their higher hydrophobicity that may result in higher intracellular drug content. This finding may suggest the application of designed fluorinated anticancer drugs to overcome acquired resistance which may develop after several regiments of treatment with a nonfluorinated chemotherapeutic agent.