Login

Journal Image
Medicinal Chemistry
ISSN (Print): 1573-4064
ISSN (Online): 1875-6638
VOLUME: 10
ISSUE: 5
DOI: 10.2174/15734064113096660046      Price:  $58









Synthesis and Dual D2 and 5-HT1A Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones

img
Author(s): Nisar Ullah
Pages 484-496 (13)
Abstract:
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.
Graphical Abstract:
Keywords:
D2 receptor, 5-HT1A receptor, 7-Piperazinyl and piperidinyl-3, 4-dihydroquinazolin-2(1H)-ones, Schizophrenia, Structure-activity relationship.
Affiliation:
Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran-31261, Saudi Arabia.