(4-(3,5-dimethylphenylamino)-1-methyl-1H-pyrrol-2-yl)(pyrrolidin-1-yl)methanone | 851590-19-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4-(3,5-dimethylphenylamino)-1-methyl-1H-pyrrol-2-yl)(pyrrolidin-1-yl)methanone
• 英文别名: [4-(3,5-dimethylanilino)-1-methylpyrrol-2-yl]-pyrrolidin-1-ylmethanone
• CAS: 851590-19-7
• 化学式: C₁₈H₂₃N₃O
• 分子量: 297.4
• InChiKey: HFWKXYQIRSHKRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4-(3,5-dimethylphenylamino)-1-methyl-1H-pyrrol-2-yl)(pyrrolidin-1-yl)methanone 、 4-(氯甲基)苯基乙酸酯 在 三乙胺 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 以76%的产率得到N-[4-[(4-acetoxybenzyl)(3,5-dimethylphenyl)amino]-1-methylpyrrole-2-carbonyl]pyrrolidine
  参考文献：
  名称：

  4-(Anilino)pyrrole-2-carboxamides: Novel non-steroidal/non-anilide type androgen antagonists effective upon human prostate tumor LNCaP cells with mutated nuclear androgen receptor

  摘要：

  Various 4-(anilino)pyrrole-2-carboxamides were designed and synthesized as novel androgen receptor (AR) antagonists without steroidal or anilide structure, based on our strategy for developing full antagonists of nuclear receptors. Introduction of a bulky N-alkyl group, such as a cyclohexylmethyl or benzyl group, increased the binding affinity for wild-type AR and the potency for growth inhibition of androgen-dependent SC-3 cells. Among the compounds obtained, N-[4-[(benzyl)(4-nitrophenyl)amino]-1-methylpyrrole-2-carbonyl]pyrrolidine (22) is as potent an AR antagonist as the typical anilide-type AR antagonists hydroxyflutamide and bicalutamide. Further, compound 22 had potent binding affinity for T877A mutated AR, and dose-dependently inhibited the testosterone-induced production of prostate-specific antigen in LNCaP cells bearing T877A AR. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.063
• 作为产物：
  描述：

  4-硝基吡咯-2-羧酸 在 palladium on activated charcoal 草酰氯 、 tris(dibenzylideneacetone)dipalladium (0) 、 氢气 、 sodium hydride 、 2-(二叔丁基膦)联苯 、 sodium t-butanolate 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 47.5h， 生成 (4-(3,5-dimethylphenylamino)-1-methyl-1H-pyrrol-2-yl)(pyrrolidin-1-yl)methanone
  参考文献：
  名称：

  Novel non-steroidal/non-anilide type androgen antagonists: discovery of 4-substituted pyrrole-2-carboxamides as a new scaffold for androgen receptor ligands

  摘要：

  We designed and synthesized novel pyrrole-2-carboxamide derivatives as androgen antagonists. Compounds 10 and 13 bearing benzylamine or aniline at the 4-position of the pyrrole ring showed moderate androgen antagonistic activity, and inhibited the androgen-dependent growth of Shionogi carcinoma cells (SC-3). Study of the structure-activity relationships of compound 13 led to a potent androgen antagonist 36, which has higher affinity than flutamide (4) for androgen nuclear receptor (AR). Thus, pyrrole-2-carboxamide is a new scaffold for developing AR antagonists. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.02.019

文献信息

• Novel non-steroidal/non-anilide type androgen antagonists: discovery of 4-substituted pyrrole-2-carboxamides as a new scaffold for androgen receptor ligands
  作者：Ken-ichi Wakabayashi、Hiroyuki Miyachi、Yuichi Hashimoto、Aya Tanatani

  DOI：10.1016/j.bmc.2005.02.019

  日期：2005.4

  We designed and synthesized novel pyrrole-2-carboxamide derivatives as androgen antagonists. Compounds 10 and 13 bearing benzylamine or aniline at the 4-position of the pyrrole ring showed moderate androgen antagonistic activity, and inhibited the androgen-dependent growth of Shionogi carcinoma cells (SC-3). Study of the structure-activity relationships of compound 13 led to a potent androgen antagonist 36, which has higher affinity than flutamide (4) for androgen nuclear receptor (AR). Thus, pyrrole-2-carboxamide is a new scaffold for developing AR antagonists. (c) 2005 Elsevier Ltd. All rights reserved.
• 4-(Anilino)pyrrole-2-carboxamides: Novel non-steroidal/non-anilide type androgen antagonists effective upon human prostate tumor LNCaP cells with mutated nuclear androgen receptor
  作者：Ken-ichi Wakabayashi、Keisuke Imai、Hiroyuki Miyachi、Yuichi Hashimoto、Aya Tanatani

  DOI：10.1016/j.bmc.2008.05.063

  日期：2008.7

  Various 4-(anilino)pyrrole-2-carboxamides were designed and synthesized as novel androgen receptor (AR) antagonists without steroidal or anilide structure, based on our strategy for developing full antagonists of nuclear receptors. Introduction of a bulky N-alkyl group, such as a cyclohexylmethyl or benzyl group, increased the binding affinity for wild-type AR and the potency for growth inhibition of androgen-dependent SC-3 cells. Among the compounds obtained, N-[4-[(benzyl)(4-nitrophenyl)amino]-1-methylpyrrole-2-carbonyl]pyrrolidine (22) is as potent an AR antagonist as the typical anilide-type AR antagonists hydroxyflutamide and bicalutamide. Further, compound 22 had potent binding affinity for T877A mutated AR, and dose-dependently inhibited the testosterone-induced production of prostate-specific antigen in LNCaP cells bearing T877A AR. (c) 2008 Elsevier Ltd. All rights reserved.