5-(4-氯苯基)-4-(3-碘苯基)-1,2-二甲基-1H-吡咯-3-羧酸乙酯 | 1384513-06-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 5-(4-氯苯基)-4-(3-碘苯基)-1,2-二甲基-1H-吡咯-3-羧酸乙酯
• 英文名称: ethyl 5-(4-chlorophenyl)-4-(3-iodophenyl)-1,2-dimethyl-1H-pyrrole-3-carboxylate
• 英文别名: 5-(4-Chloro-phenyl)-4-(3-iodo-phenyl)-1,2-dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester；ethyl 5-(4-chlorophenyl)-4-(3-iodophenyl)-1,2-dimethylpyrrole-3-carboxylate
• CAS: 1384513-06-7
• 化学式: C₂₁H₁₉ClINO₂
• 分子量: 479.745
• InChiKey: CRSXVQZEWHWONZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-氯苯基)-4-(3-碘苯基)-1,2-二甲基-1H-吡咯-3-羧酸乙酯 在 三叔丁基膦 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.0h， 生成 (R)-5-(4-chlorophenyl)-4-(3-(4-(4-(((4-((4-(dimethylamino)-1-(phenylthio)butan-2-yl)amino)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)phenyl)-1,2-dimethyl-N-(3-(4-methylpiperazin-1-yl)propyl)-1H-pyrrole-3-carboxamide
  参考文献：
  名称：

  Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

  摘要：

  Bcl-2 and Bcl-xL are key apoptosis regulators and attractive cancer therapeutic targets. We have designed and optimized a class of small-molecule inhibitors of Bcl-2 and Bcl-xL containing a 4,5-diphenyl-1H-pyrrole-3-carboxylic acid core structure. A 1.4 angstrom resolution crystal structure of a lead compound, 12, complexed with Bcl-xL has provided a basis for our optimization. The most potent compounds, 14 and 15, bind to Bcl-2 and Bcl-xL with subnanomolar K-i values and are potent antagonists of Bcl-2 and Bcl-xL in functional assays. Compounds 14 and 15 inhibit cell growth with low nanomolar IC50 values in multiple small-cell lung cancer cell lines and induce robust apoptosis in cancer cells at concentrations as low as 10 nM. Compound 14 also achieves strong antitumor activity in an animal model of human cancer.

  DOI：

  10.1021/jm300608w
• 作为产物：
  描述：

  3-碘苯甲醛 在 哌啶 、 3-乙基-5-(2-羟乙基)-4-甲基噻唑溴化物 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 29.08h， 生成 5-(4-氯苯基)-4-(3-碘苯基)-1,2-二甲基-1H-吡咯-3-羧酸乙酯
  参考文献：
  名称：

  A Potent and Highly Efficacious Bcl-2/Bcl-xL Inhibitor

  摘要：

  Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with K-i values of <1 nM and inhibits cancer cell growth with IC50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete, and durable tumor regression in vivo at a well-tolerated dose schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date.

  DOI：

  10.1021/jm4001105