4-(4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)-2-(trifluoromethyl)benzonitrile | 1607788-98-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)-2-(trifluoromethyl)benzonitrile
• 英文别名: 4-[4-(2-Hydroxypropan-2-yl)triazol-1-yl]-2-(trifluoromethyl)benzonitrile；4-[4-(2-hydroxypropan-2-yl)triazol-1-yl]-2-(trifluoromethyl)benzonitrile
• CAS: 1607788-98-6
• 化学式: C₁₃H₁₁F₃N₄O
• 分子量: 296.252
• InChiKey: NUZIVWNSCJPVEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氨基-2-三氟甲基苯甲腈 在 盐酸 、 copper(II) sulfate 、 维生素 C 作用下， 以 水 、 乙腈 为溶剂， 反应 2.83h， 生成 4-(4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Preliminary investigations into triazole derived androgen receptor antagonists

  摘要：

  A range of 1,4-substituted-1,2,3-N-phenyltriazoles were synthesized and evaluated as non-steroidal androgen receptor (AR) antagonists. The motivation for this study was to replace the N-phenyl amide portion of small molecule antiandrogens with a 1,2,3-triazole and determine effects, if any, on biological activity. The synthetic methodology presented herein is robust, high yielding and extremely rapid. Using this methodology a series of 17 N-aryl triazoles were synthesized from commercially available starting materials in less than 3 h. After preliminary biological screening at 20 and 40 mu M, the most promising three compounds were found to display IC50 values of 40-50 mu M against androgen dependent (LNCaP) cells and serve as a starting point for further structure-activity investigations. All compounds in this work were the focus of an in silico study to dock the compounds into the human androgen receptor ligand binding domain (hARLBD) and compare their predicted binding affinity with known antiandrogens. A comparison of receptor-ligand interactions for the wild type and T877A mutant AR revealed two novel polar interactions. One with Q738 of the wild type site and the second with the mutated A877 residue. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.018

文献信息

• Preliminary investigations into triazole derived androgen receptor antagonists
  作者：Jarrad M. Altimari、Birunthi Niranjan、Gail P. Risbridger、Stephanie S. Schweiker、Anna E. Lohning、Luke C. Henderson

  DOI：10.1016/j.bmc.2014.03.018

  日期：2014.5

  A range of 1,4-substituted-1,2,3-N-phenyltriazoles were synthesized and evaluated as non-steroidal androgen receptor (AR) antagonists. The motivation for this study was to replace the N-phenyl amide portion of small molecule antiandrogens with a 1,2,3-triazole and determine effects, if any, on biological activity. The synthetic methodology presented herein is robust, high yielding and extremely rapid. Using this methodology a series of 17 N-aryl triazoles were synthesized from commercially available starting materials in less than 3 h. After preliminary biological screening at 20 and 40 mu M, the most promising three compounds were found to display IC50 values of 40-50 mu M against androgen dependent (LNCaP) cells and serve as a starting point for further structure-activity investigations. All compounds in this work were the focus of an in silico study to dock the compounds into the human androgen receptor ligand binding domain (hARLBD) and compare their predicted binding affinity with known antiandrogens. A comparison of receptor-ligand interactions for the wild type and T877A mutant AR revealed two novel polar interactions. One with Q738 of the wild type site and the second with the mutated A877 residue. (C) 2014 Elsevier Ltd. All rights reserved.