10-(2-aminoethylamino)-8-methylthio-10,11-dihydrodibenzothiepin | 74611-40-8

• 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: 10-(2-aminoethylamino)-8-methylthio-10,11-dihydrodibenzothiepin
• 英文别名: N'-(3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)ethane-1,2-diamine
• CAS: 74611-40-8
• 化学式: C₁₇H₂₀N₂S₂
• 分子量: 316.491
• InChiKey: KHKXOXSZADGRDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  88.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  10-chloro-8-(methylthio)-10,11-dihydrodibenzothiepin 、 乙二胺 反应 6.0h， 以66%的产率得到10-(2-aminoethylamino)-8-methylthio-10,11-dihydrodibenzothiepin
  参考文献：
  名称：

  Neuroleptics of the 8-methylthio-10-piperazino-10,11-dihydrodibenzo[b,f]thiepin series: New compounds and new procedures

  摘要：

  将8-甲硫基二苯并[b,f]噻吩-10(11H)-酮与1-甲基哌嗪和哌嗪的单-p-甲苯磺酸酯在真空中加热，产率良好地得到烯胺IX-XI，其中第一个被还原为基本物质I（甲硫噻吩）的烯胺被锌和乙酸处理。通过氨基醇II（氧丙硫噻吩）与癸酸在N,N'-碳酰二咪唑存在下反应，并通过用1-(3-癸酰氧丙基)哌嗪替代10-氯-8-甲硫基-10,11-二氢二苯并[b,f]噻吩制得酯III（氧丙硫噻吩癸酸酯）。同一氯化合物与哌嗪的取代反应得到两个立体异构体的1,4-二取代哌嗪V。氨基醇II与辛基异氰酸酯反应得到氨基甲酸酯VI，是氧丙硫噻吩癸酸酯（III）的同分异构体。该物质在狗的抗阿波吗啡活性测试中表现出长效抗恶心的特性。合成了化合物I-III的两种新潜在代谢物（XII, XIII），并为氧丙硫噻吩（II）的另外两种潜在代谢物（XIV, XV）提供了新的药理数据。

  DOI：

  10.1135/cccc19800504

文献信息

• JILEK J.; POMYKACEK J.; DLABAC A.; BARTOSOVA M., COLLECT. CZECH. CHEM. COMMUN., 1980, 45, NO 2, 504-516
  作者：JILEK J.、 POMYKACEK J.、 DLABAC A.、 BARTOSOVA M.

  DOI：——

  日期：——
• 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.
• Neuroleptics of the 8-methylthio-10-piperazino-10,11-dihydrodibenzo[b,f]thiepin series: New compounds and new procedures
  作者：Jiří Jílek、Josef Pomykáček、Antonín Dlabač、Marie Bartošová、Miroslav Protiva

  DOI：10.1135/cccc19800504

  日期：——

  Heating of 8-methylthiodibenzo[b,f]thiepin-10(11H)-one with mono-p-toluenesulfonates of 1-methylpiperazine and piperazine in vacuo led in good yields to the enamines IX-XI, the first of which was reduced with zinc and acetic acid to the base I (methiothepin). The ester III(oxyprothepindecanoate) was obtained by reaction of the amino alcohol II (oxyprothepin) with decanoic acid in the presence of N,N'-carbonyldiimidazole and by substitution of 10-chloro-8-methylthio-10,11-dihydrobenzo[b,f]thiepin with 1-(3-decanoyloxypropyl)piperazine. The substitution reaction of the same chloro compound with piperazine gave two stereoisomeric 1,4-disubstituted piperazines V. Reaction of the amino alcohol II with octyl isocyanate afforded the carbamate VI, an isoster of oxyprothepin decanoate (III). This substance showed in the test of antiapomorphine activity in dogs the properties of a long-acting antiemetic. Two new potential metabolites (XII, XIII) of compounds I-III were synthesized and new pharmacological data are given for two further potential metabolites (XIV, XV) of oxyprothepin (II).

  将8-甲硫基二苯并[b,f]噻吩-10(11H)-酮与1-甲基哌嗪和哌嗪的单-p-甲苯磺酸酯在真空中加热，产率良好地得到烯胺IX-XI，其中第一个被还原为基本物质I（甲硫噻吩）的烯胺被锌和乙酸处理。通过氨基醇II（氧丙硫噻吩）与癸酸在N,N'-碳酰二咪唑存在下反应，并通过用1-(3-癸酰氧丙基)哌嗪替代10-氯-8-甲硫基-10,11-二氢二苯并[b,f]噻吩制得酯III（氧丙硫噻吩癸酸酯）。同一氯化合物与哌嗪的取代反应得到两个立体异构体的1,4-二取代哌嗪V。氨基醇II与辛基异氰酸酯反应得到氨基甲酸酯VI，是氧丙硫噻吩癸酸酯（III）的同分异构体。该物质在狗的抗阿波吗啡活性测试中表现出长效抗恶心的特性。合成了化合物I-III的两种新潜在代谢物（XII, XIII），并为氧丙硫噻吩（II）的另外两种潜在代谢物（XIV, XV）提供了新的药理数据。