5-((5-methoxypyridin-3-yl)methyl)-2-phenylpyridine | 1447908-60-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-((5-methoxypyridin-3-yl)methyl)-2-phenylpyridine
• 英文别名: 3-Methoxy-5-[(6-phenylpyridin-3-yl)methyl]pyridine；3-methoxy-5-[(6-phenylpyridin-3-yl)methyl]pyridine
• CAS: 1447908-60-2
• 化学式: C₁₈H₁₆N₂O
• 分子量: 276.338
• InChiKey: CMSQNLDQTGRNCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-((5-methoxypyridin-3-yl)methyl)-2-phenylpyridine 在 氢溴酸 作用下， 以 水 为溶剂， 以72%的产率得到5-((6-phenylpyridin-3-yl)methyl)pyridin-3-ol
  参考文献：
  名称：

  Cushing’s Syndrome: Development of Highly Potent and Selective CYP11B1 Inhibitors of the (Pyridylmethyl)pyridine Type

  摘要：

  Potent and selective CYP11B1 inhibitors could be promising therapeutics for the treatment of Cushing's syndrome. Optimization of Ref 1 (5-((1H-imidazol-1-yl)methyl)-2-phenylpyridine) led to compound 44 (5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine) with a 50-fold improved IC50 value of 2 nM toward human CYP11B1 and an enhanced inhibition of the rat enzyme (IC50 = 2440 nM) compared to Ref 1 (IC50 > 10000 nM). Furthermore, selectivities over CYP11B2, CYP17, and CYP19 were observed, as well as satisfying metabolic stability not only in human and rat plasma but also in liver S9 fraction. Investigation of cytotoxicity and inhibition of hepatic CYP2A6 and CYP3A4 showed that 44 fulfills first safety criteria and can be considered for further in vivo evaluation in rats.

  DOI：

  10.1021/jm400240r
• 作为产物：
  描述：

  2-溴-5-甲基吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 sodium carbonate 、 caesium carbonate 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙二醇二甲醚 、 乙醇 、 水 、 甲苯 为溶剂， 150.0 ℃ 、1.8 MPa 条件下， 反应 4.33h， 生成 5-((5-methoxypyridin-3-yl)methyl)-2-phenylpyridine
  参考文献：
  名称：

  Cushing’s Syndrome: Development of Highly Potent and Selective CYP11B1 Inhibitors of the (Pyridylmethyl)pyridine Type

  摘要：

  Potent and selective CYP11B1 inhibitors could be promising therapeutics for the treatment of Cushing's syndrome. Optimization of Ref 1 (5-((1H-imidazol-1-yl)methyl)-2-phenylpyridine) led to compound 44 (5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine) with a 50-fold improved IC50 value of 2 nM toward human CYP11B1 and an enhanced inhibition of the rat enzyme (IC50 = 2440 nM) compared to Ref 1 (IC50 > 10000 nM). Furthermore, selectivities over CYP11B2, CYP17, and CYP19 were observed, as well as satisfying metabolic stability not only in human and rat plasma but also in liver S9 fraction. Investigation of cytotoxicity and inhibition of hepatic CYP2A6 and CYP3A4 showed that 44 fulfills first safety criteria and can be considered for further in vivo evaluation in rats.

  DOI：

  10.1021/jm400240r