title: Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzim idazolone derivatives.
abstract: A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling.
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D008297:Male; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D001562:Benzimidazoles; D010880:Piperidines; D011954:Receptors, Dopamine; D013134:Spiperone; D001058:Apomorphine