Vasoactive Thiomethyl-Pyrimidines: Promising Drug Candidates with Vascular Activity

• Main Author: Andrade,Audrey N. de
• Publication Date: 2017
• Other Authors: Araújo,Alice V., Barbosa,Hugo B. W., Wanderley,Almir G., Malta,Oscar L., Anjos,Janaína V. dos
• Format: Article
• Language: eng
• Source: Journal of the Brazilian Chemical Society (Online)
• Download full: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532017000701266
• topic: pyrimidines; vascular activity; hypertension; drug discovery; ultrasound

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.