8-Cyano-10-(4-methylpiperazino)-10,11-dihydro-dibenzothiepin | 24579-08-6

• 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-Cyano-10-(4-methylpiperazino)-10,11-dihydro-dibenzothiepin
• 英文别名: 8-Cyan-10-(4-methylpiperazino)-10,11-dihydrodibenzothiepin；11-(4-methylpiperazin-1-yl)-10,11-dihydrodibenzo[b,f]thiepine-2-carbonitrile；5-(4-methylpiperazin-1-yl)-5,6-dihydrobenzo[b][1]benzothiepine-3-carbonitrile
• CAS: 24579-08-6
• 化学式: C₂₀H₂₁N₃S
• 分子量: 335.473
• InChiKey: PSBWDCHOGUBLQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-Cyano-10-(4-methylpiperazino)-10,11-dihydro-dibenzothiepin 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以100%的产率得到(11-(4-methylpiperazin-1-yl)-10,11-dihydrodibenzo[b,f]thiepin-2-yl)methanamine
  参考文献：
  名称：

  Exploring the Neuroleptic Substituent in Octoclothepin: Potential Ligands for Positron Emission Tomography with Subnanomolar Affinity for α₁-Adrenoceptors

  摘要：

  A series of 1-(10.11-dihydrodthenzo[b,f]thiepin-(10-y-l)-4-methylpiperazine analogues substituted in the 8-position of the 10,11-dihydrodibenzo[b,f]thiepine scaffold with aryl, heteroaryl. amine, and amide substituents are described. The compounds were: designed using the previously reported Liljefors-Bogeso pharmacophore model for dopamine 1)2 and alpha(1)-adrenocetor antagonists. with the aim of obtaining selective alpha(1)-adrenoceptors antagonists suitable for development as radioligands for imaging of central alpha(1)-adrenoceptors by positron emission tomography. Sixteen aryl and heteroaryl substituted octoclothepin analogues were prepared by a convergent synthesis via coupling of 1-methyl-4-(8-(4,4.5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-10,11-dihydrodibenzo[b,f]thiepin-10yl-piperazine with aryl and heteroaryl halides under palladium catalysis. The most selective compound obtained, (S)-N-(11-(4-methylpiperazin- -yl)-10,11-dihydrodibenzo[b,f]thiepin-2-yl)methyl)isobutyramide (S)-35, showed a similar subnanomolar affinity compared to alpha(1a), alpha(1b,) and alpha(1d)-adrenoceptors and a selectivity ratio of 20, 440, and 20 with respect to D-2, 5-HT2C, and H-1 receptors. respectively.

  DOI：

  10.1021/jm100652h
• 作为产物：
  描述：

  氰化锌 、 1-(8-bromo-10,11-dihydrodibenzo[b,f]thiepin-10-yl)-4-methylpiperazine 在 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 以95%的产率得到8-Cyano-10-(4-methylpiperazino)-10,11-dihydro-dibenzothiepin
  参考文献：
  名称：

  Exploring the Neuroleptic Substituent in Octoclothepin: Potential Ligands for Positron Emission Tomography with Subnanomolar Affinity for α₁-Adrenoceptors

  摘要：

  A series of 1-(10.11-dihydrodthenzo[b,f]thiepin-(10-y-l)-4-methylpiperazine analogues substituted in the 8-position of the 10,11-dihydrodibenzo[b,f]thiepine scaffold with aryl, heteroaryl. amine, and amide substituents are described. The compounds were: designed using the previously reported Liljefors-Bogeso pharmacophore model for dopamine 1)2 and alpha(1)-adrenocetor antagonists. with the aim of obtaining selective alpha(1)-adrenoceptors antagonists suitable for development as radioligands for imaging of central alpha(1)-adrenoceptors by positron emission tomography. Sixteen aryl and heteroaryl substituted octoclothepin analogues were prepared by a convergent synthesis via coupling of 1-methyl-4-(8-(4,4.5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-10,11-dihydrodibenzo[b,f]thiepin-10yl-piperazine with aryl and heteroaryl halides under palladium catalysis. The most selective compound obtained, (S)-N-(11-(4-methylpiperazin- -yl)-10,11-dihydrodibenzo[b,f]thiepin-2-yl)methyl)isobutyramide (S)-35, showed a similar subnanomolar affinity compared to alpha(1a), alpha(1b,) and alpha(1d)-adrenoceptors and a selectivity ratio of 20, 440, and 20 with respect to D-2, 5-HT2C, and H-1 receptors. respectively.

  DOI：

  10.1021/jm100652h

文献信息

• Exploring the Neuroleptic Substituent in Octoclothepin: Potential Ligands for Positron Emission Tomography with Subnanomolar Affinity for α₁-Adrenoceptors
  作者：Jesper L. Kristensen、Ask Püschl、Martin Jensen、Rune Risgaard、Claus T. Christoffersen、Benny Bang-Andersen、Thomas Balle

  DOI：10.1021/jm100652h

  日期：2010.10.14

  A series of 1-(10.11-dihydrodthenzo[b,f]thiepin-(10-y-l)-4-methylpiperazine analogues substituted in the 8-position of the 10,11-dihydrodibenzo[b,f]thiepine scaffold with aryl, heteroaryl. amine, and amide substituents are described. The compounds were: designed using the previously reported Liljefors-Bogeso pharmacophore model for dopamine 1)2 and alpha(1)-adrenocetor antagonists. with the aim of obtaining selective alpha(1)-adrenoceptors antagonists suitable for development as radioligands for imaging of central alpha(1)-adrenoceptors by positron emission tomography. Sixteen aryl and heteroaryl substituted octoclothepin analogues were prepared by a convergent synthesis via coupling of 1-methyl-4-(8-(4,4.5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-10,11-dihydrodibenzo[b,f]thiepin-10yl-piperazine with aryl and heteroaryl halides under palladium catalysis. The most selective compound obtained, (S)-N-(11-(4-methylpiperazin- -yl)-10,11-dihydrodibenzo[b,f]thiepin-2-yl)methyl)isobutyramide (S)-35, showed a similar subnanomolar affinity compared to alpha(1a), alpha(1b,) and alpha(1d)-adrenoceptors and a selectivity ratio of 20, 440, and 20 with respect to D-2, 5-HT2C, and H-1 receptors. respectively.