Adrenoceptors are the receptors for the catecholamines, adrenaline and noradrenaline. They are divided in α (α1 and α2) and β (β1, β2 and β3). α1-Adrenoceptors are subdivided in α1A, α1B and α1D. Most tissues express mixtures of α1-adrenoceptors subtypes, which appear to coexist in different densities and ratios, and in most cases their responses are probably due to the activation of more than one type. The three subtypes of α1-adrenoceptors are G-protein-coupled receptors (GPCR), specifically coupled to Gq/11. Additionally, the activation of these receptors may activate other signaling pathways or different components of these pathways, which leads to a great variety of possible cellular effects. The first clinically used α1 antagonist was Prazosin, for Systemic Arterial Hypertension (SAH). It was followed by its congeners, Terazosin and Doxazosin. Nowadays, there are many classes of α-adrenergic antagonists with different selectivity profiles. In addition to SAH, the α1-adrenoceptors are used for the treatment of Benign Prostatic Hyperplasia (BPH) and urolithiasis. This antagonism may be part of the mechanism of action of tricyclic antidepressants. Moreover, the activation of these receptors may lead to adverse effects such as orthostatic hypotension, similar to what happens with the antidepressants and with some antipsychotic. Structure-activity relationships can explain, in part, how antagonists work and how selective they can be for each one of the subtypes. However, it is necessary to develop new molecules which antagonize the α1-adrenoceptors or make chemical modifications in these molecules to improve the selectivity, pharmacokinetic profile and/or reduce the adverse effects of known drugs.

The synthesis of 2‐thiopyrimidinones through thiol‐ene coupling is reported here, resulting in 35 unpublished molecules. Thiopyrimidinones may exhibit one up to three tautomeric forms, and favoring the thiol tautomer is favored is the key to success of this reaction. Five compounds from all obtained products, those substituted with a carbonyl ester portion in the side chain, were chosen to be tested in a preliminary evaluation for human aldose reductase inhibition. All tested compounds showed an inhibition percentage equal to or >60%.