2-Guanidinobenzazoles as Building Blocks to Afford Biologically Active Derivatives

Abstract

1,3-Benzazoles (BZs) are interesting compounds in medicinal chemistry. For instance, compounds with the BZ nucleus exhibit diverse biological activities and some of them are broadly utilized in clinical applications. In this sense, medicinal chemists aim at the development of new procedures to synthesize these kinds of molecules. The 2-aminobenzimidazole 2ABI derivatives, such as Enviradine (antiviral), Astemizole (antihistaminic), and Albendazole (antimicrobial), which contain the intra-cyclic guanidine nucleus, are used in medicinal chemistry. The guanidine group, considered a super base, when bonded to a benzazole ring, results in the 2-guanidinobenzazoles (2GBZs), modifying the biological activity of these heterocycles. The structure of 2GBZs is of significance as the 10-π electron system of the aromatic benzazole ring is conjugated with the exocyclic guanidine group to acquire a planar delocalized structure. This class of molecules has at least four nitrogen atoms with free lone pairs and four labile hydrogen atoms, resulting in these compounds having amphoteric character. On the other hand, synthetic chemists have used 2GBZs as a building block to produce derivatives as medicinally important molecules. On these bases, in this work, we prepared a bibliographic review of the methodologies reported in the literature used in the synthesis of 2GBZ derivatives of pharmacological interest. We focused the investigation on 2-guanidinebenzoxazol (2GBO), 2-guanidinebenzothiazol (2GBT) and 2-guanidinebenzimidazole (2GBI) as building blocks. We found that compounds derivatives were N-substituted-2GBZs, 2-(pyrimidyl)-ABZs and 1,3,5-triazino[1,2-a]-BZs, which are described chronologically. This work will help searchers related to bioorganic chemistry, inorganic chemistry, medicinal chemistry and pharmaceutical industry in the recent methodologies to synthetize 2-guanidinobenzazole derivatives to be proposed as materials in the different areas. This topic will provide information on the utility for medicinal chemists dedicated to the design and synthesis of this class of compounds to be tested with respect to their biological activities and be proposed as new pharmacophores.