6-prop-2-ynyloxybenzo[e][1,2]oxathiine 2,2-dioxide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-prop-2-ynyloxybenzo[e][1,2]oxathiine 2,2-dioxide
• 英文别名: 6-Prop-2-ynoxy-1,2lambda6-benzoxathiine 2,2-dioxide；6-prop-2-ynoxy-1,2λ6-benzoxathiine 2,2-dioxide
• 化学式: C₁₁H₈O₄S
• 分子量: 236.248
• InChiKey: GUSAFFVHXSQLGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-prop-2-ynyloxybenzo[e][1,2]oxathiine 2,2-dioxide 、 齐多夫定 在 铜 、 四甲基氯化铵 作用下， 以 水 、 叔丁醇 为溶剂， 以78%的产率得到1-(4-(4-(((2,2-dioxidobenzo[e][1,2]oxathiin-6-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
  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：

  2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiin-6-ol 、 3-溴丙炔 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 5.0h， 以85%的产率得到6-prop-2-ynyloxybenzo[e][1,2]oxathiine 2,2-dioxide
  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

文献信息

• Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors
  作者：Emanuela Berrino、Andrea Angeli、Dmitry D. Zhdanov、Anna P. Kiryukhina、Andrea Milaneschi、Alessandro De Luca、Murat Bozdag、Simone Carradori、Silvia Selleri、Gianluca Bartolucci、Thomas S. Peat、Marta Ferraroni、Claudiu T. Supuran、Fabrizio Carta

  DOI：10.1021/acs.jmedchem.0c00636

  日期：2020.7.9

  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.