Synthesis, Pharmacophore Modeling, and Biological Evaluation of Novel 5H-Thiazolo[3,2-a]pyrimidin-5-one Derivatives as 5-HT2A Receptor Antagonists

Abstract

Novel 5H-thiazolo[3,2-a]pyrimidin-5-one derivatives linked through an ethylene bridge to various phenylpiperazine groups were prepared for evaluation as 5-HT 2A receptor antagonists. The target compounds 11a-p were prepared through the initial synthesis of the 2-chloroethyl intermediates 10a-d which were then reacted with the appropriate phenylpiperazines. All compounds were tested for their antagonistic activity on 5-HT 2A receptors using inhibition of 5-hydroxytryptophan(5-HTP)-induced head twitches in mice. Pharmacophore modeling study, based on a hypothetical pharmacophore template generated from a set of diverse known active ligands, revealed good fitting of the designed compounds to the generated hypothetical pharmacophore.

Reformulating a Pharmacophore for 5-HT2A Serotonin Receptor Antagonists

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Behavior of 2-cyano-3-(dimethylamino)-N-(4-phenylthiazol-2-yl)acrylamide towards some nitrogen nucleophiles

“…In view of the growing biological importance of fused thiazoles, particularly thiazolo[3,2-a]pyrimidines, 32,33 it was of interest to synthesize 5-oxo-3-phenyl-N-(4-phenylthiazol-2-yl)-5H-thiazolo[3,2-a]pyrimidine-6-carboxamide. This bicyclic system is considered as a thia-analogue of the natural purine bases, adenine and guanine.…”

Synthesis and biological evaluation of (phenylpiperazinyl-propyl)arylsulfonamides as selective 5-HT2A receptor antagonists

“…The 5-HT 2A receptor has been implicated as a therapeutic target for schizophrenia and depression. 4 5-HT 2 receptors were first identified in 1979 and since the early 1980s, numerous, structurally diverse antagonists of this receptor have been published ( Fig. 1).…”