Synthesis and Dual D₂ and 5-HT_1A Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones

Title:Synthesis and Dual D₂ and 5-HT_1A Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones

Volume: 10 Issue: 5

Author(s): Nisar Ullah

Affiliation:

Keywords: D₂ receptor, 5-HT_1A receptor, 7-Piperazinyl and piperidinyl-3, 4-dihydroquinazolin-2(1H)-ones, Schizophrenia, Structure-activity relationship.

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-HT_1A 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-HT_1A receptors binding affinities. The structure-activity relationship studies revealed that cyclopentenylpyridine and cyclopentenylbenzyl groups contribute significantly to the dual D₂ and 5-HT_1A receptor binding affinities of these compounds.

Cite this article as:

Ullah Nisar, Synthesis and Dual D₂ and 5-HT_1A Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones, Medicinal Chemistry 2014; 10 (5) . https://dx.doi.org/10.2174/15734064113096660046