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.

Adel Nefzi, Jon Appel, Sergey Arutyunyan, Richard A Houghten

Index: Bioorg. Med. Chem. Lett. 19(17) , 5169-75, (2009)

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Abstract

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 H(37)R(v) were identified. Some of the identified compounds are more active than the existing drug ethambutol.