2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 2.
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.
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis*; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003214:Conditioning, Classical / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D051379:Mice; D011758:Pyrroles / Q000138:chemical synthesis*; D051381:Rats; D013134:Spiperone / Q000378:metabolism
D014150:Antipsychotic Agents; D001549:Benzamides; D004146:Dioxanes; D011758:Pyrroles; D013134:Spiperone; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D001058:Apomorphine