Overview of Convergent and Divergent Synthesis of Imidazolines, Quinazolines and Thiazolidines

WALTER J. PELÁEZ

Teresina, Piauí, Brasil.

Simposio; Conferencista Invitado. Encontro Estratégico de Ciências Farmacêuticas e I Seminário Ibero Americano de P & D de Medicamentos; 2013

Departamento de Bioquímica y Farmacología – CCS Universidad Federal de Piauí

Abstract The 2-thi/oxo-imidazolidin-4-one nucleus is present in several pharmaceutically active compounds such as antimycobacterials, immunomodulators, anticonvulsivants, and antifungals. This fact has been the motivating factor for the development and improvement of its strategy of synthesis as well as the examination of its reactivity. Most of the typical synthetic methodologies usually involve several steps which inevitably lead to poor global yields of the reaction. Besides thiazolidines, in recent years, quinazolinones and their partially saturated counterparts, have come into the focus of interest because of their noteworthy pharmacological activity due to the planar RNH˗C(S)˗NR˗C(O)R moiety. Moreover, the presence of tautomerism in quinazolinones and imidazolinones has a great influence in toxicological processes; therefore, understanding their equilibrium properties and energetics is relevant when describing pharmaceutical activity. On the other hand, fluorinated compounds play a key role in medicinal chemistry since fluorine substitution in organic molecules often leads to the improvement of metabolic stability, bioavailability and protein-ligand interactions. The influence of the trifluoromethyl (˗CF3) group on physiological activity is usually related with an increase in lipophilicity, leading to the enhancement of in vivo transport characteristics. In this lecture, it will be presented our recent efforts on developing new methologies and strategies, as well as unusual aspects of the reactivity of imidazolines, quinazolines and trifluoromethylthiazolidines (figure 1). Syntheses of various structurally important compounds have been achieved by the use environmentally friendly process such us gas phase reactions and microwave irradiation.