7-(1-methyl-4-piperidyl)thieno<2,3-c>-2-benzothiepin-4(9H)-one | 85690-07-9

• 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: 7-(1-methyl-4-piperidyl)thieno<2,3-c>-2-benzothiepin-4(9H)-one
• 英文别名: 7-(1-methyl-4-piperidinyl)thieno[2,3-c][2]benzothiepin-4(9H)-one；7-(1-methylpiperidin-4-yl)-5H-thieno[2,3-c][2]benzothiepin-10-one
• CAS: 85690-07-9
• 化学式: C₁₈H₁₉NOS₂
• 分子量: 329.487
• InChiKey: BVHKZXBRUYQOSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  73.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,9-Dihydrobenzothieno<2,3-b>thiepin-4-one 、 magnesium,1-methylpiperidin-4-ide,chloride 生成 7-(1-methyl-4-piperidyl)thieno<2,3-c>-2-benzothiepin-4(9H)-one
  参考文献：
  名称：

  POLIVKA, Z.;RAJSNER, M.;METYS, J.;HOLUBEK, J.;SVATEK, E.;RYSKA, M.;PROTIV+, COLLECT. CZECH. CHEM. COMMUN., 1983, 48, N 2, 623-641

  摘要：

  DOI：

文献信息

• Antiaminic agents derived from thieno[2,3-c]-2-benzothiepin: 4-(1-Methyl-4-piperidylidene)-4,9-dihydrothieno[2,3-c]-2-benzothiepin and some related compounds
  作者：Zdeněk Polívka、Miroslav Rajšner、Jan Metyš、Jiří Holubek、Emil Svátek、Miroslav Ryska、Miroslav Protiva

  DOI：10.1135/cccc19830623

  日期：——

  In the reaction of thieno[2,3c]-2-benzothiepin-4(9H)-one (VI) with 1-methyl-4-piperidylmagnesium chloride 7-(1-methyl-4-piperidyl)thieno[2,3-c]-2-benzothiepin-4(9H)-one (VIII) is formed in addition to the expected amino alcohol VII. The title compound I was obtained by the acid catalyzed dehydration of the pure alcohol VII. Compound I (pipethiadene) has outstanding antihistamine, antiserotonin, antireserpine and anticataleptic activity and was recommended to clinical trials as a potential antimigraine agent. For pharmacokinetic and metabolic studies there were prepared the NC²H₃ analogue of pipethiadene IV and further, as potential metabolites, the demethyl analogue III, S-oxide X, demethyl S-oxide XI, N-oxide XIII and N,S-dioxide XIV. The Witting reaction of the ketone VI with 3-dimethylaminopropylidenetriphenylphosphorane resulted in a mixture of geometric isomers of 4-(3-dimethylamino-propylidene)-4,9-dihydrothieno[2,3-c]-2-benzothiepin with the strongly predominating Z-isomer XVI which was isolated from the mixture by crystallization of the hydrogen maleate. The mixture with the predominating Z-isomer XVI was converted by the treatment with 80% sulfuric acid and dilution with water to a mixture with the predominating E-isomer XV (dithiadene) which was isolated by crystallization of the hydrogen sulfate. Some further new thieno[2,3-c]-2-benzothiepin derivatives were synthesized as potential intermediates.

  在thieno[2,3c]-2-benzothiepin-4(9H)-one(VI)和1-甲基-4-哌啶基镁氯反应中，除了预期的氨基醇VII外，还形成了7-(1-甲基-4-哌啶基)thieno[2,3-c]-2-benzothiepin-4(9H)-one(VIII)。通过纯醇VII的酸催化脱水，得到了标题化合物I（pipethiadene）。化合物I具有出色的抗组胺、抗血清素、抗利血平和抗痉挛活性，并被推荐作为潜在的抗偏头痛药物进行临床试验。为了进行药代动力学和代谢研究，制备了pipethiadene的NC2H3类似物IV以及作为潜在代谢物的去甲基类似物III、S-氧化物X、去甲基S-氧化物XI、N-氧化物XIII和N，S-二氧化物XIV。ketoneVI与3-二甲基氨基丙烯基三苯基膦反应，得到4-(3-二甲基氨基丙烯基)-4,9-二氢thieno[2,3-c]-2-benzothiepin的几何异构体混合物，其中强烈占优势的是Z-异构体XVI，通过氢男酸盐结晶从混合物中分离出来。通过80%的硫酸处理和稀释水，将占优势的混合物转化为占优势的E-异构体XV（dithiadene），并通过硫酸氢盐结晶分离。还合成了一些新的thieno[2,3-c]-2-benzothiepin衍生物作为潜在的中间体。
• POLIVKA, Z.;PROTIVA, M.
  作者：POLIVKA, Z.、PROTIVA, M.

  DOI：——

  日期：——