Efficient Synthesis of Chirally Enriched 1H-Imidazo[1,2-b]pyrazole- and 4H-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. The incorporation of these bioactive scaffolds with carbohydrates adopting developed efficient synthetic protocol to synthesize new class of imidazo-pyrazole and imidazo-triazole glycohybrid molecules is reported. The carbohydrate-derived α-iodo-2,3-dihydro-4H-pyran-4-ones have been identified as suitable precursors, which were coupled with various aminopyrazoles and aminotriazoles to obtain designed glycohybrids. Thus, various imidazo-pyrazole and imidazo-triazole based glycohybrids have been prepared efficiently in good to excellent yields. These new glycohybrids were evaluated for their anticancer activity and selected compounds were found to possess submicromolar anticancer activity against MCF-7 breast cancer cell line. These molecules could potentially be developed as new chemical entities in pharmaceutical chemistry and may encourage the use of carbohydrates in stereo-divergent synthesis and drug discovery processes.

Key words

glycohybrids - imidazo-pyrazole - imidazo-triazole - stereodiversity - anticancer - α-iodoenones

Publikationsverlauf

Eingereicht: 31. Juli 2023

Angenommen nach Revision: 21. August 2023

Accepted Manuscript online:
21. August 2023

Artikel online veröffentlicht:
02. Oktober 2023

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