N-[4-fluoro-1-[[3-(1,1,2,3,3,3-hexafluoropropyl)-1-adamantyl]carbonyl]piperidin-4-yl]methyl-N-(5-methylpyridin-2-yl)methylamine | 1250831-93-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-[4-fluoro-1-[[3-(1,1,2,3,3,3-hexafluoropropyl)-1-adamantyl]carbonyl]piperidin-4-yl]methyl-N-(5-methylpyridin-2-yl)methylamine
• 英文别名: [4-Fluoro-4-[[(5-methylpyridin-2-yl)methylamino]methyl]piperidin-1-yl]-[3-(1,1,2,3,3,3-hexafluoropropyl)-1-adamantyl]methanone
• CAS: 1250831-93-6
• 化学式: C₂₇H₃₄F₇N₃O
• 分子量: 549.575
• InChiKey: KLRNAVFHYDLHNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N-(4-fluoropiperidin-4-yl)methyl-N-(5-methylpyridin-2-yl)methylamine trihydrochloride 、 3-(1,1,2,3,3,3-六氟丙基)金刚烷-1-羧酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以35%的产率得到N-[4-fluoro-1-[[3-(1,1,2,3,3,3-hexafluoropropyl)-1-adamantyl]carbonyl]piperidin-4-yl]methyl-N-(5-methylpyridin-2-yl)methylamine
  参考文献：
  名称：

  Novel Pyridylmethylamines as Highly Selective 5-HT_1A Superagonists

  摘要：

  To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT1A binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT2, alpha(1), and alpha(2)-adrenergic as well as D-1-D-4 at dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT1A were examined in vitro employing a GTP gamma S assay. The investigation guided as to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K-i value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

  DOI：

  10.1021/jm100835q

文献信息

• Novel Pyridylmethylamines as Highly Selective 5-HT_1A Superagonists
  作者：Stefan Bollinger、Harald Hübner、Frank W. Heinemann、Karsten Meyer、Peter Gmeiner

  DOI：10.1021/jm100835q

  日期：2010.10.14

  To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT1A binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT2, alpha(1), and alpha(2)-adrenergic as well as D-1-D-4 at dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT1A were examined in vitro employing a GTP gamma S assay. The investigation guided as to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K-i value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.