ethyl 2,5-dimethyl-4-(4-nitrophenyl)-1-(2-phenylethyl)-1H-pyrrole-3-carboxylate

• 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 2,5-dimethyl-4-(4-nitrophenyl)-1-(2-phenylethyl)-1H-pyrrole-3-carboxylate
• 英文别名: ethyl 2,5-dimethyl-4-(4-nitrophenyl)-1-(2-phenylethyl)-1H-pyrrole - 3-carboxylate；Ethyl 2,5-dimethyl-4-(4-nitrophenyl)-1-(2-phenylethyl)pyrrole-3-carboxylate
• 化学式: C₂₃H₂₄N₂O₄
• 分子量: 392.455
• InChiKey: YISCUJVWOCQXGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-硝基-4-[(1E)-2-硝基-1-丙烯-1-基]苯 在 盐酸 、 水 、 sodium hydride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 mineral oil 为溶剂， 反应 9.25h， 生成 ethyl 2,5-dimethyl-4-(4-nitrophenyl)-1-(2-phenylethyl)-1H-pyrrole-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

文献信息

• Androgen receptor antagonists
  申请人：Furuya Shuichi

  公开号：US20050101657A1

  公开（公告）日：2005-05-12

  The present invention provides an androgen receptor antagonistic agent and a superior prophylactic or therapeutic agent for hormone-sensitive cancer, which contain a compound of the formula: wherein, R 1 is a hydrogen atom, a group binding through a carbon atom, a group binding through a nitrogen atom, a group binding through an oxygen atom or a group binding through a sulfur atom, R 2 is a hydrogen atom, a group binding through a carbon atom, a group binding through a nitrogen atom, a group binding through an oxygen atom or a group binding through a sulfur atom, R 3 is a hydrogen atom, a hydrocarbon group which may have substituent(s), an acyl group or a heterocyclic group which may have substituent(s), R 4 is a hydrogen atom, a group binding through a carbon atom, a group binding through a nitrogen atom, a group binding through an oxygen atom or a group binding through a sulfur atom, and R 5 is a cyclic group which may have substituent(s); or a salt thereof, or its prodrug.

  本发明提供了一种雄激素受体拮抗剂，以及一种优越的预防或治疗激素敏感性癌症的药物，其含有式中的化合物：其中，R1是氢原子、通过碳原子结合的基团、通过氮原子结合的基团、通过氧原子结合的基团或通过硫原子结合的基团，R2是氢原子、通过碳原子结合的基团、通过氮原子结合的基团、通过氧原子结合的基团或通过硫原子结合的基团，R3是氢原子、可能具有取代基的碳氢基团、酰基或可能具有取代基的杂环基团，R4是氢原子、通过碳原子结合的基团、通过氮原子结合的基团、通过氧原子结合的基团或通过硫原子结合的基团，R5是可能具有取代基的环状基团；或其盐或前药。
• 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.