1-{[5-(hydroxymethyl)pyridin-3-yl]methyl}-4-(4-cyanophenyl)-2,5-dimethyl-1H-pyrrole-3-carbonitrile | 1354900-62-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-{[5-(hydroxymethyl)pyridin-3-yl]methyl}-4-(4-cyanophenyl)-2,5-dimethyl-1H-pyrrole-3-carbonitrile
• 英文别名: 4-(4-Cyanophenyl)-1-[[5-(hydroxymethyl)pyridin-3-yl]methyl]-2,5-dimethylpyrrole-3-carbonitrile
• CAS: 1354900-62-1
• 化学式: C₂₁H₁₈N₄O
• 分子量: 342.4
• InChiKey: RIFOOQKXMRKWKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  85.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,5-二氯吡咯-3-羧酸甲酯 在 吡啶 、 ammonium hydroxide 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 氯化亚砜 、 草酰氯 、 pyridinium hydrobromide perbromide 、 三溴化硼 、 sodium hydride 、 sodium carbonate 、 三乙胺 、 calcium chloride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 23.25h， 生成 1-{[5-(hydroxymethyl)pyridin-3-yl]methyl}-4-(4-cyanophenyl)-2,5-dimethyl-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

文献信息

• Design, synthesis, and biological evaluation of 4-phenylpyrrole derivatives as novel androgen receptor antagonists
  作者：Satoshi Yamamoto、Nobuyuki Matsunaga、Takenori Hitaka、Masami Yamada、Takahito Hara、Junichi Miyazaki、Takashi Santou、Masami Kusaka、Masuo Yamaoka、Naoyuki Kanzaki、Shuichi Furuya、Akihiro Tasaka、Kazumasa Hamamura、Mitsuhiro Ito

  DOI：10.1016/j.bmc.2011.10.067

  日期：2012.1

  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.