ethyl 1-butyl-5-(4-chlorophenyl)-4-(3-iodophenyl)-2-methyl-1H-pyrrole-3-carboxylate | 1402141-67-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: ethyl 1-butyl-5-(4-chlorophenyl)-4-(3-iodophenyl)-2-methyl-1H-pyrrole-3-carboxylate
• 英文别名: Ethyl 1-butyl-5-(4-chlorophenyl)-4-(3-iodophenyl)-2-methylpyrrole-3-carboxylate
• CAS: 1402141-67-6
• 化学式: C₂₄H₂₅ClINO₂
• 分子量: 521.826
• InChiKey: MVSJLIHKJHIYAK-UHFFFAOYSA-N

物化性质

• 沸点：
  548.8±50.0 °C(predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  ethyl 1-butyl-5-(4-chlorophenyl)-4-(3-iodophenyl)-2-methyl-1H-pyrrole-3-carboxylate 在 吡啶 、 copper(l) iodide 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 、 苯胺 、 L-脯氨酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (R)-1-butyl-5-(4-chlorophenyl)-4-(3-(4-(4-(4-(4-(4-hydroxypiperidin-1-yl)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)phenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-2-methyl-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  Structure-Based Discovery of BM-957 as a Potent Small-Molecule Inhibitor of Bcl-2 and Bcl-xL Capable of Achieving Complete Tumor Regression

  摘要：

  Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3-carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with K-i < 1 nM and has low nanomolar IC50 values in cell growth inhibition in cancer cell lines. Significantly, compound 30 achieves rapid, complete, and durable tumor regression in the H146 small-cell lung cancer xenograft model at a well-tolerated dose schedule.

  DOI：

  10.1021/jm3010306
• 作为产物：
  描述：

  ethyl 2-acetyl-4-(4-chlorophenyl)-3-(3-iodophenyl)-4-oxobutanoate 、 正丁胺 以 甲醇 为溶剂， 生成 ethyl 1-butyl-5-(4-chlorophenyl)-4-(3-iodophenyl)-2-methyl-1H-pyrrole-3-carboxylate
  参考文献：
  名称：

  Structure-Based Discovery of BM-957 as a Potent Small-Molecule Inhibitor of Bcl-2 and Bcl-xL Capable of Achieving Complete Tumor Regression

  摘要：

  Bcl-2 and Bcl-xL antiapoptotic proteins are attractive cancer therapeutic targets. We have previously reported the design of 4,5-diphenyl-1H-pyrrole-3-carboxylic acids as a class of potent Bcl-2/Bcl-xL inhibitors. In the present study, we report our structure-based optimization for this class of compounds based upon the crystal structure of Bcl-xL complexed with a potent lead compound. Our efforts accumulated into the design of compound 30 (BM-957), which binds to Bcl-2 and Bcl-xL with K-i < 1 nM and has low nanomolar IC50 values in cell growth inhibition in cancer cell lines. Significantly, compound 30 achieves rapid, complete, and durable tumor regression in the H146 small-cell lung cancer xenograft model at a well-tolerated dose schedule.

  DOI：

  10.1021/jm3010306