4-Chloro-3-sulfamoyl-benzoic acid prop-2-ynyl ester | 90799-75-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-Chloro-3-sulfamoyl-benzoic acid prop-2-ynyl ester
• 英文别名: prop-2-yn-1-yl 4-chloro-3-sulfamoylbenzoate
• CAS: 90799-75-0
• 化学式: C₁₀H₈ClNO₄S
• 分子量: 273.697
• InChiKey: NEVLDCXCLSYOKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.78
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  86.46
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-Chloro-3-sulfamoyl-benzoic acid prop-2-ynyl ester 、 齐多夫定 在 铜 、 四甲基氯化铵 作用下， 以 水 、 叔丁醇 为溶剂， 以21%的产率得到(1-((2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl 4-chloro-3-sulfamoylbenzoate
  参考文献：
  名称：

  Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors

  摘要：

  Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7h, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with K-I values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC(50 )values ranging from 5.2 to 9.1 mu M). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.

  DOI：

  10.1021/acs.jmedchem.0c00636
• 作为产物：
  描述：

  4-氯-3-磺酰胺基苯甲酸 、 2-丙炔-1-醇 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 以40%的产率得到4-Chloro-3-sulfamoyl-benzoic acid prop-2-ynyl ester
  参考文献：
  名称：

  Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors

  摘要：

  Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7h, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with K-I values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC(50 )values ranging from 5.2 to 9.1 mu M). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.

  DOI：

  10.1021/acs.jmedchem.0c00636