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 phenylephrineinduced contraction in isolated rat aorta, suggesting that they may act as alpha-1 antagonists and, therefore, are candidates for anti-hypertensive drugs.

Ultrasound‐Assisted Multicomponent Reactions, Organometallic and Organochalcogen Chemistry

“…In 2017, Malta and co‐workers described a protocol to access bioactive pyrimidinone derivatives 53 through an US‐assisted MCR between aromatic aldehydes 1 , ethyl cyanoacetate 32 and 2‐methyl‐2‐thiopseudourea hemisulfate 52 , in the presence of equivalent amounts K 2 CO 3 and EtOH as solvent, in poor to good yields after 2 h under sonication conditions (Scheme ).…”

Biologically active thio‐pyrimidinones from base‐catalyzed thiol‐ene coupling with maleimides

“…Our research group is involved in synthesis and biological tests of pyrimidines and their derivatives for a long time [7,[25][26][27][28]. Once we started to work with thiopyrimidinones, we wondered if this class of thioheterocycle would undergo the thiol-ene reaction, since the main tautomer is the thione form.…”

“…Thiouracil and its analogues have been widely applied in therapeutics due to their biological actions such as antimicrobial [1], anti-inflammatory [2,3], anticancer [4][5][6], vasoactive [7], and antiplatelet activities [8]. A successful example is propylthiouracil (PTU), which is an orally active drug used in hyperthyroidism treatment (Figure 1) [9].…”