8-(5-(benzo[d]thiazol-2-yl)-5-oxopentyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one | 1382352-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 8-(5-(benzo[d]thiazol-2-yl)-5-oxopentyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
• 英文别名: 8-[5-(1,3-Benzothiazol-2-yl)-5-oxopentyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 1382352-79-5
• 化学式: C₂₅H₂₈N₄O₂S
• 分子量: 448.589
• InChiKey: OCZGPPRWTUONED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  93.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(benzo[d]thiazol-2-yl)-5-hydroxypentan-1-one 在 咪唑 、 碘 、 potassium carbonate 、 三苯基膦 、 potassium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 12.58h， 生成 8-(5-(benzo[d]thiazol-2-yl)-5-oxopentyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
  参考文献：
  名称：

  Benzothiazoles as probes for the 5HT1A receptor and the serotonin transporter (SERT): A search for new dual-acting agents as potential antidepressants

  摘要：

  The synthesis and evaluation of several benzothiazole-based compounds are described in an attempt to identify novel dual-acting 5HT(1A) receptor and SERT inhibitors as new antidepressants. Binding affinities at the 5HT(1A) receptor and the serotonin transporter do not appear to be congruent and other areas of the binding sites would need to be explored in order to improve binding simultaneously at both sites. Compounds 20 and 23 show moderate binding affinity at the 5HT(1A) receptor and the SERT site and thus, have the potential to be further explored as dual-acting agents. In addition, compound 20 binds with low affinity to the dopamine transporter (DAT), the norepinephrine transporter (NET) and 5HT(2C) receptor, which are desirable properties as selectivity for SERT (and not DAT or NET) is associated with an absence of cardiovascular side effects. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2012.03.042

文献信息

• Development of CNS multi-receptor ligands: Modification of known D2 pharmacophores
  作者：Jagan R. Etukala、Xue Y. Zhu、Suresh V.K. Eyunni、Edem K. Onyameh、Edward Ofori、Barbara A. Bricker、Hye J. Kang、Xi-Ping Huang、Bryan L. Roth、Seth Y. Ablordeppey

  DOI：10.1016/j.bmc.2016.06.011

  日期：2016.8

  Several known D-2 pharmacophores have been explored as templates for identifying ligands with multiple binding affinities at dopamine and serotonin receptors considered as clinically relevant receptors in the treatment of neuropsychiatric diseases. This approach has resulted in the identification of ligands that target multiple CNS receptors while avoiding others associated with deleterious effects. In particular, compounds 11, 15 and 22 may have potential for further development as antipsychotic agents as they favorably interact with the clinically relevant receptors including D2R, 5-HT1AR, and 5-HT7R. We have also identified the pair of compounds 11 and 10 as high affinity D2R ligands with and without SERT binding affinities, respectively. These differential binding profiles endow the pair with the potential for evaluating SERT contributions to antipsychotic drug activity in animal behavioral models. In addition, compound 11 has no significant affinity for 5-HT2CR and binds only moderately to the H1R, suggesting it may not induce weight gain or sedation when used clinically. Taken together, compound 11 displays an interesting pharmacological profile that necessitates the evaluation of its functional and in vivo effects in animal models which are currently ongoing. Published by Elsevier Ltd.
• Benzothiazoles as probes for the 5HT1A receptor and the serotonin transporter (SERT): A search for new dual-acting agents as potential antidepressants
  作者：Xue Y. Zhu、Jagan R. Etukala、Suresh V.K. Eyunni、Vincent Setola、Bryan L. Roth、Seth Y. Ablordeppey

  DOI：10.1016/j.ejmech.2012.03.042

  日期：2012.7

  The synthesis and evaluation of several benzothiazole-based compounds are described in an attempt to identify novel dual-acting 5HT(1A) receptor and SERT inhibitors as new antidepressants. Binding affinities at the 5HT(1A) receptor and the serotonin transporter do not appear to be congruent and other areas of the binding sites would need to be explored in order to improve binding simultaneously at both sites. Compounds 20 and 23 show moderate binding affinity at the 5HT(1A) receptor and the SERT site and thus, have the potential to be further explored as dual-acting agents. In addition, compound 20 binds with low affinity to the dopamine transporter (DAT), the norepinephrine transporter (NET) and 5HT(2C) receptor, which are desirable properties as selectivity for SERT (and not DAT or NET) is associated with an absence of cardiovascular side effects. Published by Elsevier Masson SAS.