title: Synthesis and dual D2 and 5-HT1A receptor binding affinities of 5-piperidinyl and 5-piperazinyl-1H-benzo[d]imidazol-2(3H)-ones.
abstract: A series of new 5-piperidinyl and 5-piperazinyl-1H-benzo[d]imidazol-2(3H)-ones have been synthesized and evaluated for dual D2 and 5-HT1A receptor binding affinities. The synthesized ligands are structurally related to bifeprunox, a potential atypical antipsychotic, having potent D2 receptor antagonist and 5-HT1A receptor agonist properties. The Suzuki-Miyaura reaction of cyclic vinyl boronate with appropriate aryl halide yielded arylpiperidine, which was eventually transformed to piperidinyl-1H-benzo[d]imidazol-2(3H)-one. The reductive amination of the latter with appropriate biarylaldehdyes rendered the synthesis of 5-piperidinyl-1H-benzo[d]imidazol-2(3H)-ones. Likewise, the Buchwald-Hartwig coupling reactions of 1-boc-piperazine with appropriate aryl halide and subsequent removal of the boc group rendered arylpiperazine. The reductive amination of the latter with appropriate biarylaldehdyes accomplished the synthesis of 5-piperazinyl-1H-benzo[d]imidazol-2(3H)-ones. The structure-activity relationship studies showed that cyclopentenylpyridine and cyclopentenylbenzyl groups contribute significantly to the dual D2 and 5-HT1A receptor binding affinities of these compounds.
authors.affiliation: Chemistry Department & Centre of Research Excellence in Nanotechnology, King Fahd University of Petroleum & Minerals , Dhahran , Saudi Arabia.
authors.forename: Nisar
authors.initials: N
authors.lastname: Ullah
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D001562:Benzimidazoles; D010879:Piperazines; D010880:Piperidines; D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor; D044282:Receptor, Serotonin, 5-HT1A