**2. Modification of Drug Sca**ff**olds: Analogs of Known Drugs or the Literature Compounds**

The initiation points for this approach were natural product scaffolds or scaffolds known to have activity against MTB cells in vitro but did not possess drug-like properties. Efforts to address this were mainly medicinal-chemistry driven, focused on understanding structure–activity relationship (SAR) on potency and animal toxicity. The advances in chemistry in terms of novel reactions and the use of combinatorial chemistry resulted in rapid diversification of key scaffolds to yield potent analogs. Some of the examples of scaffolds were the nitroimidazoles and several newer rifampicins, isoniazid, and ethambutol analogs [9–12].
