10-demethoxy-10-N-amino-7-N-deacetylcolchicine | 114537-83-6

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 英文名称: 10-demethoxy-10-N-amino-7-N-deacetylcolchicine
• 英文别名: deacetylcolchiceinamide；(S)-7,10-diamino-1,2,3-trimethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one；(S)-7,10-Diamino-1,2,3-trimethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-on；(7S)-7,10-diamino-1,2,3-trimethoxy-6,7-dihydrobenzo[a]heptalen-9(5H)-one；(7S)-7,10-diamino-1,2,3-trimethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one
• CAS: 114537-83-6
• 化学式: C₁₉H₂₂N₂O₄
• 分子量: 342.395
• InChiKey: VLEZHRZYWFPNJF-ZDUSSCGKSA-N

物化性质

• 沸点：
  620.7±55.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  96.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  10-demethoxy-10-N-amino-7-N-deacetylcolchicine 在 水 、 sodium carbonate 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 37.0h， 生成 N-(trifluoroacetyl)deacetylcolchiceinamide
  参考文献：
  名称：

  Fluorinated colchicinoids: antitubulin and cytotoxic properties

  摘要：

  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.

  DOI：

  10.1021/jm00115a026
• 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 在 ammonium hydroxide 作用下， 反应 48.0h， 生成 10-demethoxy-10-N-amino-7-N-deacetylcolchicine
  参考文献：
  名称：

  Fluorinated colchicinoids: antitubulin and cytotoxic properties

  摘要：

  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.

  DOI：

  10.1021/jm00115a026

文献信息

• Colchicine. Derivatives of Trimethylcolchicinic Acid^1,2
  作者：Robert F. Raffauf、Ann L. Farren、Glenn E. Ullyot

  DOI：10.1021/ja01117a044

  日期：1953.11
• Kiselew, Zhurnal Obshchei Khimii, 1959, vol. 29, p. 2445,2448; engl. Ausg. S. 2409, 2411
  作者：Kiselew

  DOI：——

  日期：——
• 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.