3-trifluoromethyl-11-(4-methylpiperazino)-10,11-dihydrodibenzothiepin | 47484-93-5

• 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: 3-trifluoromethyl-11-(4-methylpiperazino)-10,11-dihydrodibenzothiepin
• 英文别名: 1-Methyl-4-[2-(trifluoromethyl)-5,6-dihydrobenzo[b][1]benzothiepin-5-yl]piperazine
• CAS: 47484-93-5
• 化学式: C₂₀H₂₁F₃N₂S
• 分子量: 378.461
• InChiKey: LYSTXBLNUSUUQY-UHFFFAOYSA-N

物化性质

• 沸点：
  424.8±45.0 °C(Predicted)
• 密度：
  1.265±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  31.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  <2-(3-trifluoromethylphenylthio)phenyl>acetic acid 在 N-甲基哌嗪 、 盐酸 、 sodium tetrahydroborate 、 PPA 作用下， 以 1,4-二氧六环 、 sodium hydroxide 、 乙醇 、 氯仿 、 邻二氯苯 、 苯 为溶剂， 反应 19.0h， 生成 3-trifluoromethyl-11-(4-methylpiperazino)-10,11-dihydrodibenzothiepin
  参考文献：
  名称：

  Fluorinated analogues of the tricyclic neuroleptics; 7-Fluoro and 7-trifluoromethyl derivative of 10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepin

  摘要：

  3-氟硫代苯酚与(2-碘苯基)乙酸反应，生成酸 VIII，经过多磷酸环化得到酮 XII。第一个标题化合物 VI 是通过中间体 XV 和 XVIII 制备而成。将酮 XII 与1-甲基哌嗪在四氯化钛存在下处理，得到烯胺 XXIII。类似地制备的酸 IX 经过环化得到酮 XIII。副产物是二酸 X 和烯醇内酯 XXIV，经过碱水解得到酮酸 XXV。第二个标题化合物 VII 的合成是从酮 XIII 经过中间体 XVI 和 XIX 进行的。10,11-二氢二苯并[ b,f ]噻吩-3,11-二醇 (XVII) 经过甲磺酰氯处理，并通过与1-甲基哌嗪反应生成1-甲基哌嗪与二苯并[ b,f ]噻吩-3-醇盐 (XXII) 和 1-甲基-4-(甲磺酰基)哌嗪 (XXVI)。化合物 VI 具有较低的中枢抑制和痉挛活性，相应的烯胺 XXIII 在这两方面非常强效。三氟甲基衍生物 VII 具有神经阻滞剂的特性，但其抑制和痉挛活性比 8-三氟甲基异构体低十倍。

  DOI：

  10.1135/cccc19801086

文献信息

• LIGANDS THAT TARGET HEPATITIS C VIRUS E2 PROTEIN
  申请人：BALHORN Rodney

  公开号：US20160361311A1

  公开（公告）日：2016-12-15

  Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, the crystal structure of the core of the HCV E2 protein (E2c) has been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2's interaction with different host factors. By targeting sites containing conserved E2 amino acids in the CD81 binding site on HCV E2, one might also be able to develop drugs that block HCV infection in a genotype-independent manner. Using the E2c structure as a template, a structural model of the E2 protein core (residues 421-645) was developed that includes the three amino acid segments that are not present in the E2c crystal structure. Blind docking of a diverse library of 1715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2:CD81 interaction. Surface plasmon resonance was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of hepatocytes by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited hepatocyte infection by HCV genotypes 1a, 1b, 2a, 2b, 4a and 6a with IC50's ranging from 2.2 μM to 4.6 μM. Methods are described for preventing or treating HCV infection using small molecule inhibitors such as 281816 that target E2 and disrupt its interactions.
• Fluorinated analogues of the tricyclic neuroleptics; 7-Fluoro and 7-trifluoromethyl derivative of 10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepin
  作者：Karel Šindelář、Emil Svátek、Jiří Holubek、Miroslav Ryska、Jiřina Metyšová、Zdeněk Šedivý、Miroslav Protiva

  DOI：10.1135/cccc19801086

  日期：——

  Reaction of 3-fluorothiophenol with (2-iodophenyl)acetic acid gave the acid VIII which was cyclized with polyphosphoric acid to the ketone XII. The first title compound VI was prepared via the intermediates XV and XVIII. Treatment of the ketone XII with 1-methylpiperazine in the presence of titanium tetrachloride resulted in the enamine XXIII. The similarly prepared acid IX was cyclized to the ketone XIII. By-products were the di-acid X and the enol-lactone XXIV, affording by alkaline hydrolysis the keto acid XXV. The synthesis of the second title compound VII was carried out from the ketone XIII via the intermediates XVI and XIX. 10,11-Dihydrodibenzo[b,f]thiepin-3,11-diol (XVII) gave by treatment with methanesulfonyl chloride and by the following reaction with 1-methylpiperazine the salt of 1-methylpiperazine with dibenzo[b,f]thiepin-3-ol (XXII) and 1-methyl-4-(methylsulfonyl)piperazine (XXVI)). Whereas the compound VI has low central depressant and cataleptic activity, the corresponding enamine XXIII is very potent in both lines. The trifluoromethyl derivative VII has the character of a neuroleptic but its depressant and cataleptic activity are ten times lower than those of the 8-trifluoromethyl isomer.

  3-氟硫代苯酚与(2-碘苯基)乙酸反应，生成酸 VIII，经过多磷酸环化得到酮 XII。第一个标题化合物 VI 是通过中间体 XV 和 XVIII 制备而成。将酮 XII 与1-甲基哌嗪在四氯化钛存在下处理，得到烯胺 XXIII。类似地制备的酸 IX 经过环化得到酮 XIII。副产物是二酸 X 和烯醇内酯 XXIV，经过碱水解得到酮酸 XXV。第二个标题化合物 VII 的合成是从酮 XIII 经过中间体 XVI 和 XIX 进行的。10,11-二氢二苯并[ b,f ]噻吩-3,11-二醇 (XVII) 经过甲磺酰氯处理，并通过与1-甲基哌嗪反应生成1-甲基哌嗪与二苯并[ b,f ]噻吩-3-醇盐 (XXII) 和 1-甲基-4-(甲磺酰基)哌嗪 (XXVI)。化合物 VI 具有较低的中枢抑制和痉挛活性，相应的烯胺 XXIII 在这两方面非常强效。三氟甲基衍生物 VII 具有神经阻滞剂的特性，但其抑制和痉挛活性比 8-三氟甲基异构体低十倍。