Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
Eur J Med Chem. 2012 Jul;53:124-32. doi: 10.1016/j.ejmech.2012.03.042. Epub 2012 Apr 4.
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.
本文描述了几种苯并噻唑类化合物的合成和评价，旨在寻找新型双重作用 5-HT（1A）受体和 SERT 抑制剂作为新型抗抑郁药。5-HT（1A）受体和血清素转运体的结合亲和力似乎不一致，需要探索结合位点的其他区域，以便同时提高两个部位的结合。化合物 20 和 23 在 5-HT（1A）受体和 SERT 部位具有中等的结合亲和力，因此有可能进一步探索作为双重作用的药物。此外，化合物 20 对多巴胺转运体（DAT）、去甲肾上腺素转运体（NET）和 5-HT（2C）受体的亲和力较低，这是一种理想的特性，因为 SERT 的选择性（而不是 DAT 或 NET）与不存在心血管副作用有关。
