Prospects of Pre-clinical [6.6.0] Bicyclic Nitrogen Heterocycles in the Treatment of Tuberculosis

One of the major challenges in the successful treatment of tuberculosis (TB) infection is the emergence of anti-microbial resistance in Mycobacterium tuberculosis (Mtb), which is one of the major contributing factors in TB infection reaching its current pandemic scale. Quinoline is a bicyclic nitrogen heterocyclic scaffold, which is the core of a number of anti-TB drugs, pre-clinical and clinical candidates. This chapter focuses on deciphering the anti-TB prospects of derivatives of the lesser explored bioisosteres of quinoline: quinoxaline, quinazoline, 1,8-naphthyridine, deazapteridine, and pteridine in terms of their whole cell activity against Mtb, structure activity relationship, drug-likeness predicted based on pharmacokinetic/ADME properties and the relevant medicinal chemistry properties to assess the drug-likeness of the most potent derivatives. The chapter also compares the most active molecules containing these scaffolds based on their predicted pharmacokinetic and medicinal chemistry properties with the aim to select the most prospective molecules on the basis of their drug-likeness.