The Thienopyridine and Furopyridine Rings: New Pharmacophores with Potential Antipsychotic Activity

Article abstract of DOI:10.1021/jm00126a002

Two new arylpiperazine derivatives, the 4-(1-piperazinyl)thieno- and -furo<3,2-c>pyridine ring systems, have been synthesized and appended via tetramethylene chains to various imide rings.Target compounds from each series were found to have significant activity in the blockade of apomorphine stereotypy and apomorphine-induced climbing, the Sidman avoidance response, and the conditioned avoidance response.In addition, while potent affinity for serotonin 5-HT₁ and 5-HT₂ receptors was observed for both the thieno- and furo<3,2-c>pyridine derivatives,the interaction of these molecules with the dopamine D2 receptor was weak.Electrophysiological studies of the lead prototypes from each series, involving compounds 22 and 33, indicate these two molecules have distinctively different effects on dopamine neurons in areas A9 and A10.Despite the similarity these molecules share in their behavioral indices of antipsychotic acivity, it is likely that the thieno- and furo<3,2-c>pyridine rings employ different mechanisms to achieve this convergence of biological effects.