N7-(2-dimethylaminoethyl)-5,N2-dimethyl-3-phenylsulfonylpyrazolo[1,5-a ]pyrimidine-2,7-diamine hydrochloride | 1220645-13-5

• 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: N7-(2-dimethylaminoethyl)-5,N2-dimethyl-3-phenylsulfonylpyrazolo[1,5-a ]pyrimidine-2,7-diamine hydrochloride
• 英文别名: 3-(benzenesulfonyl)-7-N-[2-(dimethylamino)ethyl]-2-N,5-dimethylpyrazolo[1,5-a]pyrimidine-2,7-diamine;hydrochloride
• CAS: 1220645-13-5
• 化学式: C₁₈H₂₄N₆O₂S*ClH
• 分子量: 424.954
• InChiKey: UDIODMZLHRLPSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.31
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-methyl-2-(methylamino)-3-(phenylsulfonyl)pyrazolo[1,5-a]pyrimidin-7-ol 在 三氯氧磷 作用下， 以 1,4-二氧六环 、 环丁砜 为溶剂， 反应 4.0h， 生成 N7-(2-dimethylaminoethyl)-5,N2-dimethyl-3-phenylsulfonylpyrazolo[1,5-a ]pyrimidine-2,7-diamine 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

文献信息

• Synthesis and Structure–Activity Relationship (SAR) of (5,7-Disubstituted 3-phenylsulfonyl-pyrazolo[1,5-<i>a</i>]pyrimidin-2-yl)-methylamines as Potent Serotonin 5-HT₆ Receptor (5-HT₆R) Antagonists
  作者：Alexandre V. Ivachtchenko、Elena S. Golovina、Madina G. Kadieva、Volodymyr M. Kysil、Oleg D. Mitkin、Sergey E. Tkachenko、Ilya M. Okun

  DOI：10.1021/jm201079g

  日期：2011.12.8

  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.