5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine | 1373311-09-1

• 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-methylpyridin-3-yl)methyl)-2-phenylpyridine
• 英文别名: 2-Phenyl-5-(5-methyl-3-pyridinylmethyl)pyridine；3-methyl-5-[(6-phenylpyridin-3-yl)methyl]pyridine
• CAS: 1373311-09-1
• 化学式: C₁₈H₁₆N₂
• 分子量: 260.338
• InChiKey: FLLIVPRKOUZFTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine 在 重水 、 四丁基碘化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以97 %的产率得到5-((5-methylpyridin-3-yl)methyl)-2-phenylpyridine-4-d
  参考文献：
  名称：

  吡啶的电化学γ-选择性氘化

  摘要：

  在此，我们首先报道了吡啶通过 H/D 交换的 γ 选择性氘化反应，无需预先安装的导向基团和可转化官能团。电化学过程提供了一种在温和条件下生产 γ-氘代吡啶的有吸引力的方法。电化学方法广泛的底物范围、优异的氘掺入性和显着的选择性使其适用于药物分子的后期修饰。

  DOI：

  10.1021/acs.orglett.4c01296
• 作为产物：
  描述：

  2-溴-5-甲基吡啶 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 sodium carbonate 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 乙醇 、 水 、 甲苯 为溶剂， 反应 8.0h， 生成 5-((5-methylpyridin-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

文献信息

• [EN] SELECTIVE CYP11B1 INHIBITORS FOR THE TREATMENT OF CORTISOL DEPENDENT DISEASES<br/>[FR] INHIBITEURS SÉLECTIFS DE CYP11B1 POUR LE TRAITEMENT DE MALADIES DÉPENDANTES DU CORTISOL
  申请人：UNIV SAARLAND

  公开号：WO2012052540A1

  公开（公告）日：2012-04-26

  The present invention relates to compounds which selectively inhibit CYP11B1. Preferably, the compounds of the present invention do not substantially inhibit CYP11B2. Moreover, the compounds of the present invention do not substantially inhibit CYP17 and/or CYP19, either. Amongst other applications of the compounds of the present invention, they can be used for the treatment of Cushing's syndrome or metabolic disease.

  本发明涉及选择性抑制CYP11B1的化合物。优选，本发明的化合物不显著抑制CYP11B2。此外，本发明的化合物也不显著抑制CYP17和/或CYP19。在本发明的化合物的其他应用中，它们可用于治疗库欣综合症或代谢性疾病。
• SELECTIVE CYP11B1 INHIBITORS FOR THE TREATMENT OF CORTISOL DEPENDENT DISEASES
  申请人：Hartmann Rolf

  公开号：US20140155407A1

  公开（公告）日：2014-06-05

  The present invention relates to compounds which selectively inhibit CYP11B1. Preferably, the compounds of the present invention do not substantially inhibit CYP11B2. Moreover, the compounds of the present invention do not substantially inhibit CYP17 and/or CYP19, either. Amongst other applications of the compounds of the present invention, they can be used for the treatment of Cushing's syndrome or metabolic disease.

  本发明涉及一种选择性抑制CYP11B1的化合物。优选地，本发明的化合物不会显著抑制CYP11B2。此外，本发明的化合物也不会显著抑制CYP17和/或CYP19。在本发明化合物的其他应用中，它们可用于治疗库欣综合征或代谢疾病。
• Selective CYP11B1 inhibitors for the treatment of cortisol dependent diseases
  申请人：Hartmann Rolf

  公开号：US09394290B2

  公开（公告）日：2016-07-19

  The present invention relates to compounds which selectively inhibit CYP11B1. Preferably, the compounds of the present invention do not substantially inhibit CYP11B2. Moreover, the compounds of the present invention do not substantially inhibit CYP17 and/or CYP19, either. Amongst other applications of the compounds of the present invention, they can be used for the treatment of Cushing's syndrome or metabolic disease.

  本发明涉及选择性抑制CYP11B1的化合物。优选地，本发明的化合物不会实质性地抑制CYP11B2。此外，本发明的化合物也不会实质性地抑制CYP17和/或CYP19。除了本发明化合物的其他应用外，它们可以用于库欣综合征或代谢疾病的治疗。
• US9394290B2
  申请人：——

  公开号：US9394290B2

  公开（公告）日：2016-07-19
• Cushing’s Syndrome: Development of Highly Potent and Selective CYP11B1 Inhibitors of the (Pyridylmethyl)pyridine Type
  作者：Juliette Emmerich、Qingzhong Hu、Nina Hanke、Rolf W. Hartmann

  DOI：10.1021/jm400240r

  日期：2013.8.8

  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.