8,10-dichloro-10,11-dihydrodibenzothiepin | 13459-65-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫平类
• 英文名称: 8,10-dichloro-10,11-dihydrodibenzothiepin
• 英文别名: 2,11-dichloro-10,11-dihydro-dibenzo[b,f]thiepine；8,10-Dichlor-10,11-dihydrodibenzothiepin；8, 10-Dichloro-10,11-dihydrodibenzo[b,f]thiepine；3,5-dichloro-5,6-dihydrobenzo[b][1]benzothiepine
• CAS: 13459-65-9
• 化学式: C₁₄H₁₀Cl₂S
• 分子量: 281.205
• InChiKey: JMRJBBBEEZDLAL-UHFFFAOYSA-N

物化性质

• 熔点：
  105-106 °C
• 沸点：
  365.6±42.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  25.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  8,10-dichloro-10,11-dihydrodibenzothiepin 以74%的产率得到
  参考文献：
  名称：

  BARTL V.; HOLUBEK J.; NEMEC J.; BARTOSOVA M.; PROTIVA M., COLLECT CZECH. CHEM. COMMUN., 1978, 43, NO 9, 2477-2443

  摘要：

  DOI：

文献信息

• Cataleptic and noncataleptic neuroleptic agents: Synthesis and pharmacology of 4-(2-chloro and 8-chloro substituted 10,11-dihydrodibenzo[b,f]thiepin-10-yl)piperazine-1-ylalkyl ethers and sulfides
  作者：Vladimír Valenta、Zdeněk Prošek、Jiřina Metyšová、Martin Valchář、Antonín Dlabač、Miroslav Protiva

  DOI：10.1135/cccc19851070

  日期：——

  The title compounds Iab-Viab were prepared by substitution reactions of 2,11-dichloro- and 2,10-dichloro-10,11-dihydrodibenzo[b,f]thiepin with 1-(2-methoxyethyl)piperazine, 1-(3-methoxypropyl)piperazine, 1-(2-ethoxyethyl)piperazine, 1-(2-phenoxyethyl)piperazine, 1-(2-methylthioethyl)piperazine and 1-(2-phenylthioethyl)piperazine; they were transformed to hydrochlorides, maleates or methanesulfonates. Compounds of series a (8-chloro derivatives) are neuroleptics, with relatively strong cataleptic, antiapomorphine and central depressant activities (Ia, IIa, IIIa,Va) unless the volume and lipophilicity of the N-substituent exceeds certain limits (IVa and VIa are almost nontoxic and little active). Compounds of series b (2-chloro derivatives) are noncataleptic and devoid of the antiapomorphine potency; only two of them (IIb, Vb), however, showed a more pronounced effect in the test of influencing the turnover and metabolism of dopamine in the rat brain striatum.

  标题化合物是通过2,11-二氯和2,10-二氯-10,11-二氢二苯并[bf]噻吩与1-(2-甲氧基乙基)哌嗪、1-(3-甲氧基丙基)哌嗪、1-(2-乙氧基乙基)哌嗪、1-(2-苯氧基乙基)哌嗪、1-(2-甲硫氧乙基)哌嗪和1-(2-苯硫氧乙基)哌嗪的取代反应制备的；它们转化为盐酸盐、马来酸盐或甲磺酸盐。系列a的化合物(8-氯衍生物)是神经阻滞药，具有相对较强的猫状症、抗阿波莫啡和中枢抑制活性(Ia、IIa、IIIa、Va)，除非N-取代基的体积和亲脂性超过一定限制，否则IVa和VIa几乎无毒且活性较低。系列b的化合物(2-氯衍生物)不具猫状症，也没有抗阿波莫啡的作用；然而，其中只有两种(IIb、Vb)在影响大鼠脑纹状体多巴胺的转化和代谢测试中显示出更显著的效果。
• Tricyclic potential neuroleptics: 2-chloro-11-[4-(4-fluoroaralkyl)piperazino]-10,11-dihydrodibenzo[b,f]thiepins and related compounds
  作者：Václav Bártl、Antonín Dlabač、Miroslav Protiva

  DOI：10.1135/cccc19803182

  日期：——

  Alkylation of 1-ethoxycarbonylpiperazine with 4-fluorobenzyl bromide, 2-(4-fluorophenyl)ethyl bromide and 4,4-bis(4-fluorophenyl)butyl bromide gave the carbamates IIa, IIb and IIf. Two further similar compounds (IIc, IId) were obtained by reactions of 1-(2-chloroethyl)-4-ethoxycarbonylpiperazine with 4-fluorophenol, and with 4-fluorothiophenol, respectively. Hydrolysis of carbamates IIa-f resulted in piperazine derivatives IIIa-f affording the title compounds by substitution reactions with 2,11-dichloro-10,11-dihydrodibenzo[b,f]thiepin. Out of the compounds prepared only the fluorophenethyl derivative Ib and the fluorobenzoylpropyl derivative Ie maintain the neuroleptic character, i.e. clear central depressant and cataleptic activity.

  用4-氟苄基溴、2-(4-氟苯基)乙基溴和4,4-双(4-氟苯基)丁基溴对1-乙氧羰基哌嗪进行烷基化反应，得到了羰酸酯IIa、IIb和IIf。通过1-(2-氯乙基)-4-乙氧羰基哌嗪与4-氟苯酚和4-氟硫酚反应，还得到了两种类似的化合物(IIc、IId)。羰酸酯IIa-f的水解产生哌嗪衍生物IIIa-f，通过与2,11-二氯-10,11-二氢二苯并[b,f]噻吩的取代反应得到了目标化合物。制备的化合物中，只有氟苯乙基衍生物Ib和氟苯甲酰丙基衍生物Ie保持了神经类药物的特性，即具有明显的中枢抑制和僵直活性。
• N-substituted azaheterocyclic compounds
  申请人：Novo Nordisk A/S

  公开号：US06060468A1

  公开（公告）日：2000-05-09

  The present invention relates to novel N-substituted azaheterocyclic compounds of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.1a, R.sup.2, R.sup.2a, p, r and s are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for treatment of indications caused by or related to secretion and circulation of insulin antagonising peptides.

  本发明涉及新型N-取代的杂环化合物，其一般式为##STR1##其中X、Y、Z、R.sup.1、R.sup.1a、R.sup.2、R.sup.2a、p、r和s如本说明书详细部分所定义，或其盐，以及它们的制备方法、含有它们的组合物，以及它们用于临床治疗疼痛、高度敏感和/或炎症病症的用途，其中C纤维通过引起神经源性疼痛或炎症发挥病理生理作用，以及它们用于治疗由分泌和循环胰岛素拮抗肽引起或相关的指示的用途。
• ——
  作者：

  DOI：——

  日期：——
• Protiva, Miroslav; Jilek, Jiri; Cervena, Irena, Collection of Czechoslovak Chemical Communications, 1986, vol. 51, # 11, p. 2598 - 2616
  作者：Protiva, Miroslav、Jilek, Jiri、Cervena, Irena、Pomykacek, Josef、Bartl, Vaclav、et al.

  DOI：——

  日期：——