Despite massive global efforts tuberculosis rates continue to climb and drug-resistance rates are rising to alarming levels. Discovering new agents for treating this bacterial pathogen poses unique challenges, but these challenges have been faced throughout the entire modern history of research into anti-infectives. This review looks back at every decade since the 1940s and summarizes the most important drugs developed during each decade highlighting the lessons learned during these successful medicinal chemistry programs. Looking forward we must accelerate the integration of these past lessons with the impressive advances that have been made in the basic understanding of the biology of this disease.
Keywords: Tuberculosis, drug development, streptomycin, rifampicin, isoniazid, linezolid, nitroimidazoles, diarylquinoline, benzothiazinone, drug-resistance, anti-infectives, chemotherapy, second-line drugs, genomically-informed
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