2-Phenylpyrroles as Conformationally Restricted Benzamide Analogues. A New Class of Potential Antipsychotics. 2

Article abstract of DOI:10.1021/jm00118a011

A series of 2-phenylpyrrole Mannich bases was synthesized and screened in pharmacological models for antipsychotic activity and extrapyramidal effects.Structure modifications of 5-(4-fluorophenyl)-2-<<4-(2-methoxyphenyl)-1-piperazinyl>methyl>pyrrole (1), the prototype of a new class of sodium-independent atypical dopamine D-2 antagonists, resulted in 2-<<4-(7-benzofuranyl)-1-piperazinyl>methyl>-5-(4-fluorophenyl)pyrrole (15), which was an even more potent and selective D-2 antagonist than the parent compound.The excellent oral activity in the apomorphine-induced climbing behavior and the conditioned avoidance response tests and the absence of catalepsy make this compound particularly promising as a potential antipsychotic with a low propensity to induce acute extrapyramidal side effects.