Ofori Edward, Zhu Xue Y, Etukala Jagan R, Bricker Barbara A, Ablordeppey Seth Y
Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
Bioorg Med Chem. 2016 Nov 15;24(22):5730-5740. doi: 10.1016/j.bmc.2016.09.019. Epub 2016 Sep 10.
Diseases of the CNS are often complex and involve multiple receptor systems and thus, the treatment options for these diseases must focus on targeting the multiple receptors implicated in the various disorders. Schizophrenia and depression are examples of such diseases and their pharmacotherapy thus depends on agents which target multiple receptors including the dopamine, serotonin and even cholinergic receptors at the same time. In our previous campaign to find multi-receptor ligands, we have identified the benzothiazole 1a as an initial lead molecule. In the current work, we have expanded the structure affinity relationship (SAFIR) of 1a resulting in the identification of a partially restrained butyrophenone 3j as a potent and selective dual 5-HT and 5-HT receptor ligand. It is expected that compound 3j may serve as a new lead for further development in our search for newer and novel ligands with the potential to treat diseases of CNS origin.
中枢神经系统疾病通常很复杂，涉及多个受体系统，因此，这些疾病的治疗方案必须专注于针对各种疾病中涉及的多个受体。精神分裂症和抑郁症就是这类疾病的例子，它们的药物治疗因此依赖于同时作用于包括多巴胺、5-羟色胺甚至胆碱能受体在内的多个受体的药物。在我们之前寻找多受体配体的研究中，我们已确定苯并噻唑1a为初始先导分子。在当前的工作中，我们扩展了1a的结构亲和力关系（SAFIR），从而确定了一种部分受限的丁酰苯3j，它是一种有效且选择性的5-羟色胺和5-羟色胺受体双重配体。预计化合物3j可能作为新的先导物，用于我们进一步寻找有潜力治疗中枢神经系统源性疾病的更新颖配体的研究中。
