Synthesis and Dual D2 and 5-HT1A Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones
Affiliation: Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran-31261, Saudi Arabia.
A series of new 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones has been synthesized. The
described compounds are structurally related to adoprazine, a potential atypical antipsychotic bearing potent D2 receptor
antagonist and 5-HT1A receptor agonist properties. Suitably modified aryl bromides were prepared and condensed with
tert-butyl piperazine-1-carboxylate to afford the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one.
Likewise Suzuki-Miyaura cross-coupling reaction of cyclic vinyl boronate with appropriate aryl bromides rendered
piperidinyl-3,4-dihydroquinazolin-2(1H)-one. The reductive amination of the piperazinyl and piperidinyl-3,4-
dihydroquinazolin-2(1H)-ones with suitably designed biarylaldehydes accomplished the synthesis of these title compounds.
The described compounds were screened for D2 and 5-HT1A receptors binding affinities. The structure-activity relationship
studies revealed that cyclopentenylpyridine and cyclopentenylbenzyl groups contribute significantly to the dual
D2 and 5-HT1A receptor binding affinities of these compounds.
Keywords: D2 receptor, 5-HT1A receptor, 7-Piperazinyl and piperidinyl-3, 4-dihydroquinazolin-2(1H)-ones, Schizophrenia,
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