Parallel synthesis of chiral pentaamines and pyrrolidine containing bis-heterocyclic libraries. Multiple scaffolds with multiple building blocks: A double diversity for the identification of new antitubercular compounds

Combinatorial chemistry offers a unique opportunity for the synthesis and screening of large numbers of compounds and significantly enhances the prospect of finding new drugs. Collaborative efforts with the Tuberculosis Antimicrobial Acquisition & Coordinating Facility (TAACF), have led to the identification of submicromolar novel antitubercular hits. Chiral pentaamines and bis-heterocyclic compounds with 90–100% inhibition against Mycobacterium tuberculosis strain H37Rv were identified. Some of the identified compounds are more active than the existing drug ethambutol.

Graphical abstractThe solid phase synthesis of a chiral pentaamine and pyrrolidine bis-heterocyclic libraries with four positions of diversity (R1–R4) is reported. Screening these libraries yielded the identification of compounds with 90–100% inhibition against Mycobacterium tuberculosis strain H37Rv at low MIC values.Figure optionsDownload full-size imageDownload as PowerPoint slide