Vasoactive thiomethyl-pyrimidines: Promising drug candidates with vascular activity

Abstract

Pyrimidines and their derivatives are present in various biologically active molecules. Most of the synthetic methods employed to achieve the pyrimidinone ring consist of two stages: The synthesis of a Michael intermediate from an aldehyde and an "active methylene" containing compound; and the condensation of this intermediate with a molecule containing an uranium moiety. This may take one to two days of laboratory work. In this paper we describe a new methodology in which these derivatives are obtained via multicomponent synthesis mediated by ultrasound in only 2 hours. In order to obtain water-soluble pyrimidinone derivatives, our previous compounds were further converted into their sodium salts. In pharmacologic studies, these salts inhibited phenylephrine-induced contraction in isolated rat aorta, suggesting that they may act as alpha-1 antagonists and, therefore, are candidates for anti-hypertensive drugs.