Nematollahi Alireza, Aminimoghadamfarouj Noushin, Church William Bret
Faculty of Pharmacy A15, The University of Sydney, Sydney NSW 2006, Australia.
Med Chem. 2014;10(6):541-9. doi: 10.2174/1573406410666131229150746.
Due to the wide range of chemical structures and variety of mechanisms of action of antischizophrenic agents, it is difficult to identify and confirm a common pharmacophore. The present review summarizes various pharmacophore models for antischizophrenic activity including those based on the new targets, the kynurenine aminotransferase (KATs), which may facilitate the development of novel drugs. Some models illustrate the structural differences of compounds with mechanisms of action considered similar, and yet others demonstrate pharmacophore models for similar chemical classes of compounds for which the mechanism of antischizophrenic action is still not clear. In this study, we discuss the pharmacophore models for antipsychotics including phenothiazine, butyrophenone, thioxanthene, and atypical agents along with the novel antischizophrenic agents which are inhibitors of KATs isozymes.
由于抗精神分裂症药物的化学结构范围广泛且作用机制多样,因此很难识别和确认一个共同的药效基团。本综述总结了抗精神分裂症活性的各种药效基团模型,包括基于新靶点犬尿氨酸转氨酶(KATs)的模型,这可能有助于新型药物的开发。一些模型阐明了作用机制被认为相似的化合物的结构差异,而其他模型则展示了抗精神分裂症作用机制仍不明确的类似化学类别的化合物的药效基团模型。在本研究中,我们讨论了抗精神病药物的药效基团模型,包括吩噻嗪、丁酰苯、硫杂蒽以及非典型药物,以及作为KATs同工酶抑制剂的新型抗精神分裂症药物。