Efficient Synthesis of Chirally Enriched 1 H -Imidazo[1,2- b ]pyrazole- and 4 H -Imidazo[1,2- b ][1,2,4]triazole-Based Bioactive Glycohybrids

Abstract

Carbohydrates, traditionally known for their energy-providing role, have gained significant attention in drug discovery due to their diverse bioactivities and stereodiversity. However, pure carbohydrate molecules often exhibit limited bioactivity and suboptimal chemical and physical characteristics. To address these challenges, bioactive scaffolds have been incorporated into carbohydrate to enhance their bioactivity and improve their overall properties. Among the various heterocyclic structural motifs known for their pharmacological properties, imidazo-pyrazole and imidazo-triazole skeleton have gained larger attention among synthetic and medicinal chemists as they possess good biological and pharmacological properties. Present work deals with the incorporation of carbohydrate moieties into these bioactive scaffolds (imidazo-pyrazole and imidazo-triazole skelton) to develop an efficient synthetic protocol for new class of imidazo-pyrazole and imidazo-triazole glycohybrid molecules. The carbohydrate derived α-iodo-2,3-dihydro-4H-pyran-4-ones have been identified as suitable precursors which were coupled with various amino-pyrazoles and amino-triazoles to obtain designed glycohybrids. Thus, various imidazo-pyrazole and imidazo-triazole based glycohybrids have been prepared efficiently in good to very good yield. These new glycohybrids evaluated for their anticancer activity and selected compounds were found to possess submicromolar anticancer activity. These molecules could potentially be developed as new chemical entities and may encourage the use of carbohydrates in stereo-divergent synthesis and drug discovery processes.