2-[(4-Acetyl-4-phenylpiperidin-1-yl)methyl]-4,6-dimethyl-[1,2]thiazolo[5,4-b]pyridin-3-one

• 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: 2-[(4-Acetyl-4-phenylpiperidin-1-yl)methyl]-4,6-dimethyl-[1,2]thiazolo[5,4-b]pyridin-3-one
• 化学式: C₂₂H₂₅N₃O₂S
• 分子量: 395.525
• InChiKey: JQEZGWZGQIGIKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  78.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-乙酰-4-苯基哌啶盐酸盐 、 2-hydroxymethyl-4,6-dimethylisothiazolo[5,4-b]pyridin-3(2H)-one 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 13.0h， 生成 2-[(4-Acetyl-4-phenylpiperidin-1-yl)methyl]-4,6-dimethyl-[1,2]thiazolo[5,4-b]pyridin-3-one
  参考文献：
  名称：

  Synthesis and in vivo pharmacology of new derivatives of isothiazolo[5,4-b]pyridine of Mannich base type

  摘要：

  Recently we reported on 2H-4,6-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridine (V), which exhibited high anorectic action in animal models as a result of stimulation of serotoninergic system. This paper describes the synthesis of the series 3-5 of analogues of V prepared from 2-hydroxymethyl-4,6-dimethylisothiazolopyridine (2) and corresponding 4-substituted-piperazines(piperidines) or tetrahydroisoquinoline. The 12 compounds obtained were screened in standard CNS tests in in vivo (mice and rats). In contrast to V, none of its analogues showed serotoninergic activity, whereas several of these compounds were found to be active as weak to moderate analgesic agents. According to X-ray and molecular modeling studies the different pharmacological profile of V and its o-OCH, analog 3a, taken as an example, should be referred back to the conformational restriction incorporated by the o-substitution rather than effects of different lipophlicity or basicity of these compounds. (C) 2001 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01157-0

文献信息

• Synthesis and in vivo pharmacology of new derivatives of isothiazolo[5,4-b]pyridine of Mannich base type
  作者：Wiesław Malinka、Zbigniew Karczmarzyk、Maria Sieklucka-Dziuba、Mirosław Sadowski、Zdzisław Kleinrok

  DOI：10.1016/s0014-827x(01)01157-0

  日期：2001.12

  Recently we reported on 2H-4,6-dimethyl-2-[(4-phenylpiperazin-1-yl)methyl]-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridine (V), which exhibited high anorectic action in animal models as a result of stimulation of serotoninergic system. This paper describes the synthesis of the series 3-5 of analogues of V prepared from 2-hydroxymethyl-4,6-dimethylisothiazolopyridine (2) and corresponding 4-substituted-piperazines(piperidines) or tetrahydroisoquinoline. The 12 compounds obtained were screened in standard CNS tests in in vivo (mice and rats). In contrast to V, none of its analogues showed serotoninergic activity, whereas several of these compounds were found to be active as weak to moderate analgesic agents. According to X-ray and molecular modeling studies the different pharmacological profile of V and its o-OCH, analog 3a, taken as an example, should be referred back to the conformational restriction incorporated by the o-substitution rather than effects of different lipophlicity or basicity of these compounds. (C) 2001 Elsevier Science S.A. All rights reserved.