[6-(2-dimethylaminoethyl)-5,7-dimethyl-3-phenylsulfonylpyrazolo[1,5-a]pyrimidin-2-yl]methylamine hydrochloride | 1220646-05-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: [6-(2-dimethylaminoethyl)-5,7-dimethyl-3-phenylsulfonylpyrazolo[1,5-a]pyrimidin-2-yl]methylamine hydrochloride
• 英文别名: 3-(benzenesulfonyl)-6-[2-(dimethylamino)ethyl]-N,5,7-trimethylpyrazolo[1,5-a]pyrimidin-2-amine;hydrochloride
• CAS: 1220646-05-8
• 化学式: C₁₉H₂₅N₅O₂S*ClH
• 分子量: 423.967
• InChiKey: VSMIYCKYMHUHMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.75
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  聚合甲醛 、 [6-(2-aminoethyl)-5,7-dimethyl-3-(phenylsulfonyl)pyrazolo[1,5-a]pyrimidin-2-yl]methylamine 在 三乙酰氧基硼氢化钠 、 盐酸 作用下， 以 二氯甲烷 、 1,4-二氧六环 、 丙酮 为溶剂， 反应 15.0h， 以61%的产率得到[6-(2-dimethylaminoethyl)-5,7-dimethyl-3-phenylsulfonylpyrazolo[1,5-a]pyrimidin-2-yl]methylamine hydrochloride
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationship (SAR) of (5,7-Disubstituted 3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methylamines as Potent Serotonin 5-HT₆ Receptor (5-HT₆R) Antagonists

  摘要：

  Syntheses, biological evaluation as 5-HT6 receptor (5-HT6R) antagonists, and structure activity relationships for a series of novel 5,7-disubstituted (3-arylsulfonyl-pyrazolo[1,5-a]pyrimidins are disclosed. The molecule conformational flexibility in the series is restricted by formation of the intramolecular hydrogen bond between 3-sulfo and 2-methylamino groups, which renders high potency and high selectivity to block serotonin-induced responses in HEK-293 cells stably expressing human 5-HT6R. In this work, we tested the hypothesis if addition of a positively ionizable group (PI) to the pyrimidine ring of the scaffold members in positions 5, 6, or 7 could further increase their 5HT(6)R blocking potency. We show that the presence of the PI group with small substituents does not substantially affect either potency or selectivity of the ligands while causing substantial changes in their cLogP values. This provides a possibility for designing of the 5HT(6)R ligands with modified ADME characteristics without grossly affecting efficiency of their interaction with the receptor. In respect to the structure-activity relationship (SAR), among other physiochemical parameters, only the molecule size and shape (described by gyration radii) showed a clear tendency for more compact molecules to be more potent antagonists of this receptor.

  DOI：

  10.1021/jm201079g