2,2,2-三氟-N-[(7S)-1,2,3-三甲氧基-10-甲硫基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基]乙酰胺 | 76129-16-3

• 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: 2,2,2-三氟-N-[(7S)-1,2,3-三甲氧基-10-甲硫基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基]乙酰胺
• 英文名称: N-<5,6,7,9-tetrahydro-1,2,3-trimethoxy-9-oxo-10-(methylthio)-9-oxobenzoheptalen-7-yl>-(S)-2,2,2-trifluoroacetamide
• 英文别名: N-(trifluoroacetyl)deacetylthiocolchicine；N-[5,6,7,9-tetrahydro-1,2,3-trimethoxy-9-oxo-10-(methylthio)-9-oxobenzo[a]heptalen-7-yl]-(S)-2,2,2-trifluoroacetamide；2,2,2-trifluoro-N-[(7S)-1,2,3-trimethoxy-10-methylsulfanyl-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 76129-16-3
• 化学式: C₂₂H₂₂F₃NO₅S
• 分子量: 469.482
• InChiKey: LNELBQZKXVASLW-AWEZNQCLSA-N

物化性质

• 沸点：
  686.0±55.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 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：
  99.2
• 氢给体数：
  1
• 氢受体数：
  9

SDS

反应信息

• 作为反应物：
  描述：

  2,2,2-三氟-N-[(7S)-1,2,3-三甲氧基-10-甲硫基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基]乙酰胺 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 264.0h， 生成 thiodemecolcine
  参考文献：
  名称：

  Synthesis and biological effects of novel thiocolchicines. 3. evaluation of N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, and O-ethyldemethylthiocolchicines. New synthesis of thiodemecolcine and antileukemic effects of 2-demethyl- and 3-demethylthiocolchicine

  摘要：

  Novel and known analogues of thiocolchicine were evaluated in vitro in a tubulin binding assay and in vivo in mice for acute toxicity and in the P388 lymphocytic leukemia assay. This evaluation included N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, thiodemecolcine and its methyl carbamate, and O-ethyl ethers of demethylthiocolchicines. Selective ether cleavage of thiodemecolcine with concentrated sulfuric acid at 50 degree C afforded the 2-demethyl congener, characterized as its N,O-diacetyl derivative. Several of the compounds showed high potency in the tubulin binding assay, matching the potency of colchicine. Several N-(alkoxycarbonyl)deacetylcolchicines (carbamates) exhibited strong binding affinity to tubulin but had only weak activities against the P388 tumor system, suggesting that other factors besides tubulin binding may be important for the biological effects. The compounds potent in the tubulin binding assay and in the P388 leukemia assay in mice were generally also toxic to mice in the acute toxicity test, showing thus a similar behavior of thiocolchicines to that observed earlier with colchicines. A considerable amount of data collected for 2-demethyl- and 3-demethylthiocolchicine suggests that the latter represents a broad-spectrum antitumor agent of considerable promise and possibly a less toxic substitute for colchicine.

  DOI：

  10.1021/jm00147a014
• 作为产物：
  描述：

  (7S)-7-氨基-1,2,3-三甲氧基-10-甲硫基-6,7-二氢-5H-苯并[g]庚搭烯-9-酮 、 三氟乙酸酐 在 sodium carbonate 作用下， 以 乙醚 为溶剂， 反应 5.0h， 以79.5%的产率得到2,2,2-三氟-N-[(7S)-1,2,3-三甲氧基-10-甲硫基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基]乙酰胺
  参考文献：
  名称：

  Synthesis and biological effects of novel thiocolchicines. 3. evaluation of N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, and O-ethyldemethylthiocolchicines. New synthesis of thiodemecolcine and antileukemic effects of 2-demethyl- and 3-demethylthiocolchicine

  摘要：

  Novel and known analogues of thiocolchicine were evaluated in vitro in a tubulin binding assay and in vivo in mice for acute toxicity and in the P388 lymphocytic leukemia assay. This evaluation included N-acyldeacetylthiocolchicines, N-(alkoxycarbonyl)deacetylthiocolchicines, thiodemecolcine and its methyl carbamate, and O-ethyl ethers of demethylthiocolchicines. Selective ether cleavage of thiodemecolcine with concentrated sulfuric acid at 50 degree C afforded the 2-demethyl congener, characterized as its N,O-diacetyl derivative. Several of the compounds showed high potency in the tubulin binding assay, matching the potency of colchicine. Several N-(alkoxycarbonyl)deacetylcolchicines (carbamates) exhibited strong binding affinity to tubulin but had only weak activities against the P388 tumor system, suggesting that other factors besides tubulin binding may be important for the biological effects. The compounds potent in the tubulin binding assay and in the P388 leukemia assay in mice were generally also toxic to mice in the acute toxicity test, showing thus a similar behavior of thiocolchicines to that observed earlier with colchicines. A considerable amount of data collected for 2-demethyl- and 3-demethylthiocolchicine suggests that the latter represents a broad-spectrum antitumor agent of considerable promise and possibly a less toxic substitute for colchicine.

  DOI：

  10.1021/jm00147a014

文献信息

• 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.