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 | 26195-65-3

• 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: 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
• 英文名称: N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzoheptalen-7-yl)-(S)-2,2,2-trifluoroacetamide
• 英文别名: (-)-N-(trifluoroacetyl)deacetylcolchicine；N-deacetyl-N-(trifluoroacetyl)colchicine；N-trifluoroacetyldeacetylcolchicine；N-Trifluoracetyl-desacetyl-colchicin；Colchicine, 17,17,17-trifluoro-；2,2,2-trifluoro-N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 26195-65-3
• 化学式: C₂₂H₂₂F₃NO₆
• 分子量: 453.415
• InChiKey: MCHADYPYCJQLMV-AWEZNQCLSA-N

物化性质

• 沸点：
  681.3±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯甲烷、二氯甲烷、DMSO、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  9

SDS

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  (+/-)-N-(trifluoroacetyl)deacetylcolchiceine 在 sodium carbonate 、 potassium carbonate 作用下， 以 甲醇 、 乙醚 、 水 、 丙酮 为溶剂， 反应 5.5h， 生成 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
  参考文献：
  名称：

  Facile conversion of natural colchicine into (.+-.)-congeners and (+)-enantiomers including 2-demethyl analogs

  摘要：

  DOI：

  10.1021/jo00363a021

文献信息

• Kashiwada, Yoshiki; Sun, Li; Tatematsu, Hiroshi, Heterocycles, 1993, vol. 36, # 11, p. 2531 - 2540
  作者：Kashiwada, Yoshiki、Sun, Li、Tatematsu, Hiroshi、Bastow, Kenneth F.、Lee, Kuo-Hsiung

  DOI：——

  日期：——
• Quantitative structure-activity relationships of colchicines against P388 leukemia in mice
  作者：Frank R. Quinn、John A. Beisler

  DOI：10.1021/jm00135a004

  日期：1981.3

  A quantitative structure-activity relationship (QSAR) was derived for colchicine and 14 analogues acting against P388 lymphocytic leukemia in mice. Twelve additional compounds were synthesized to reinforce and confirm the correlation. The final correlation indicates that there is a parabolic dependence of antitumor potency on the partition coefficient with log P0=1.17. When an amino nitrogen is present on the B ring, increased potency is favored by acylation of the nitrogen. The most potent compound of the series was the 7-fluoroacetamide analogue. Strong electron-withdrawing groups substituted at the 10 position of the tropolone ring destroy activity. Electron-releasing groups at position 10 improve potency slightly but have a limited effect.
• 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.
• Facile conversion of natural colchicine into (.+-.)-congeners and (+)-enantiomers including 2-demethyl analogs
  作者：Raymond Dumont、Arnold Brossi、J. V. Silverton

  DOI：10.1021/jo00363a021

  日期：1986.6
• 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.