ethyl 2-chloro-5-{[3-cyano-4-(4-cyanophenyl)-2-methyl-1H-pyrrol-1-yl]methyl}pyridine-3-carboxylate | 1354900-60-9

• 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 2-chloro-5-{[3-cyano-4-(4-cyanophenyl)-2-methyl-1H-pyrrol-1-yl]methyl}pyridine-3-carboxylate
• CAS: 1354900-60-9
• 化学式: C₂₂H₁₇ClN₄O₂
• 分子量: 404.856
• InChiKey: DODOQWRHDHNBQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  91.7
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-chloro-5-{[3-cyano-4-(4-cyanophenyl)-2-methyl-1H-pyrrol-1-yl]methyl}pyridine-3-carboxylate 在 sodium tetrahydroborate 、 calcium chloride 、 柠檬酸 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 14.0h， 以55%的产率得到1-{[6-chloro-5-(hydroxymethyl)pyridin-3-yl]methyl}-4-(4-cyanophenyl)-2-methyl-1H-pyrrole-3-carbonitrile
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 4-phenylpyrrole derivatives as novel androgen receptor antagonists

  摘要：

  A series of 4-phenylpyrrole derivatives D were designed, synthesized, and evaluated for their potential as novel orally available androgen receptor antagonists therapeutically effective against castration-resistant prostate cancers. 4-Phenylpyrrole compound 1 exhibited androgen receptor (AR) antagonistic activity against T877A and W741C mutant-type ARs as well as wild-type AR. An arylmethyl group incorporated into compound 1 contributed to enhancement of antagonistic activity. Compound 4n, 1-{[6-chloro-5-(hydroxymethyl)pyridin-3-yl]methyl}-4-(4-cyanophenyl)-2,5-dimethyl-1H-pyrrole-3-carbonitrile exhibited inhibitory effects on tumor cell growth against the bicalutamide-resistant LNCaP-cxD2 cell line as well as the androgen receptor-dependent JDCaP cell line in a mouse xenograft model. These results demonstrate that this series of pyrrole compounds are novel androgen receptor antagonists with efficacy against prostate cancer cells, including castration-resistant prostate cancers such as bicalutamide-resistant prostate cancer. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.067
• 作为产物：
  描述：

  4-(4-cyanophenyl)-2-methyl-1H-pyrrole-3-carboxamide 在 吡啶 、 草酰氯 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.25h， 生成 ethyl 2-chloro-5-{[3-cyano-4-(4-cyanophenyl)-2-methyl-1H-pyrrol-1-yl]methyl}pyridine-3-carboxylate
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 4-phenylpyrrole derivatives as novel androgen receptor antagonists

  摘要：

  A series of 4-phenylpyrrole derivatives D were designed, synthesized, and evaluated for their potential as novel orally available androgen receptor antagonists therapeutically effective against castration-resistant prostate cancers. 4-Phenylpyrrole compound 1 exhibited androgen receptor (AR) antagonistic activity against T877A and W741C mutant-type ARs as well as wild-type AR. An arylmethyl group incorporated into compound 1 contributed to enhancement of antagonistic activity. Compound 4n, 1-{[6-chloro-5-(hydroxymethyl)pyridin-3-yl]methyl}-4-(4-cyanophenyl)-2,5-dimethyl-1H-pyrrole-3-carbonitrile exhibited inhibitory effects on tumor cell growth against the bicalutamide-resistant LNCaP-cxD2 cell line as well as the androgen receptor-dependent JDCaP cell line in a mouse xenograft model. These results demonstrate that this series of pyrrole compounds are novel androgen receptor antagonists with efficacy against prostate cancer cells, including castration-resistant prostate cancers such as bicalutamide-resistant prostate cancer. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.067