1-bromo-3,3-dimethyl-4-(naphthalen-2-yl)butan-2-one | 1258315-97-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-bromo-3,3-dimethyl-4-(naphthalen-2-yl)butan-2-one
• CAS: 1258315-97-7
• 化学式: C₁₆H₁₇BrO
• 分子量: 305.214
• InChiKey: VSZHUXCNLPVIIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.37
• 重原子数：
  18.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  17.07
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  4-{1-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenol 、 1-bromo-3,3-dimethyl-4-(naphthalen-2-yl)butan-2-one 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-1-(4-(3-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3-methylphenyl)pentan-3-yl)-2-methylphenoxy)-3,3-dimethyl-4-(naphthalen-2-yl)butan-2-one
  参考文献：
  名称：

  Novel selective anti-androgens with a diphenylpentane skeleton

  摘要：

  We have proposed a multi-template approach for drug development, focusing on similar fold structures of proteins, and have effectively generated lead compounds for several drug targets. Modification of these polypharmacological lead compounds is then needed to generate target-selective compounds. In the work presented here, we aimed at separation of the anti-androgen activity and vitamin D activity of previously identified diphenylpentane lead compounds. Based on the determined X-ray crystal structures of androgen receptor and vitamin D receptor, bulky substituents were introduced at the t-butyl group in the lead compounds 2 and 3. As a result of this structural development, we obtained 16c, which exhibits more potent anti-androgen activity (IC(50): 0.13 mu M) than clinically used anti-androgen bicalutamide (IC(50): 0.67 mu M) with 30-fold selectivity over vitamin D activity. This result indicates that lead compounds obtained via the multi-template approach can indeed be structurally modified to generate target-selective compounds. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.011
• 作为产物：
  描述：

  C₁₆H₁₈O 在 溴 作用下， 以 1,4-二氧六环 为溶剂， 以100%的产率得到1-bromo-3,3-dimethyl-4-(naphthalen-2-yl)butan-2-one
  参考文献：
  名称：

  Novel selective anti-androgens with a diphenylpentane skeleton

  摘要：

  We have proposed a multi-template approach for drug development, focusing on similar fold structures of proteins, and have effectively generated lead compounds for several drug targets. Modification of these polypharmacological lead compounds is then needed to generate target-selective compounds. In the work presented here, we aimed at separation of the anti-androgen activity and vitamin D activity of previously identified diphenylpentane lead compounds. Based on the determined X-ray crystal structures of androgen receptor and vitamin D receptor, bulky substituents were introduced at the t-butyl group in the lead compounds 2 and 3. As a result of this structural development, we obtained 16c, which exhibits more potent anti-androgen activity (IC(50): 0.13 mu M) than clinically used anti-androgen bicalutamide (IC(50): 0.67 mu M) with 30-fold selectivity over vitamin D activity. This result indicates that lead compounds obtained via the multi-template approach can indeed be structurally modified to generate target-selective compounds. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.011