2-chloro-4-[4-(4-fluorophenyl)-3,5-dimethyl-1H-pyrazol-1-yl]benzonitrile | 1370642-81-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloro-4-[4-(4-fluorophenyl)-3,5-dimethyl-1H-pyrazol-1-yl]benzonitrile
• 英文别名: 2-Chloro-4-[4-(4-fluorophenyl)-3,5-dimethylpyrazol-1-yl]benzonitrile
• CAS: 1370642-81-1
• 化学式: C₁₈H₁₃ClFN₃
• 分子量: 325.773
• InChiKey: PEIRPJCUYQRMEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯-4-氟苯腈 在 溴 、 sodium hydride 、 sodium carbonate 、 溶剂黄146 作用下， 以 二甲氧基乙烷 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.18h， 生成 2-chloro-4-[4-(4-fluorophenyl)-3,5-dimethyl-1H-pyrazol-1-yl]benzonitrile
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole derivatives as novel androgen receptor antagonists

  摘要：

  A series of 4-arylmethyl-1-phenylpyrazole and 4-aryloxy-1-phenylpyrazole compounds B were designed, synthesized, and evaluated for their potential as new-generation androgen receptor (AR) antagonists therapeutically effective against castration-resistant prostate cancer (CRPC). Introduction of a bulky amide substituent (R-2) to the terminal aryl ring of the 4-arylmethyl group favored the reduction of agonistic activity and improved the pharmacokinetic (PK) properties. Similarly, introduction of a bulky substituent in the 4-aryloxy derivatives also resulted in improved PK properties. Compounds 28h and 44b exhibited potent antitumor effects against a CRPC model of LNCaP-hr cell line in a mouse xenograft model. On the contrary, bicalutamide showed only partial suppression of tumor growth. These results suggest that the novel pyrazole derivatives are new-generation AR antagonists, different from the 'first-generation' antagonists such as bicalutamide in a CRPC treatment model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.005