Synthesis of Functionalised Chromonyl-pyrimidines and Their Potential as Antimycobacterial Agents

Drug-resistant strains of Mycobacterium tuberculosis are on the rise and have resulted in an urgent need to develop new tuberculosis (TB) drugs. Herein, the development of chromonyl-pyrimidines as a new TB drug scaffold is presented. A library of eleven chromonyl-pyrimidines was synthesised, from which lead compound 6-((2-amino-6-methylpyrimidin-4-yl)amino)-3-benzoyl-2-phenyl-4H-chromen-4-one (MIC=36 mu M against M. tuberculosis) was identified. A second-generation library of seven aryl-substituted chromonyl-pyrimidines was then prepared, with six chromonyl-pyrimidines exhibiting an improved M. tuberculosis growth inhibition (MIC=12.5 mu M). From this work, the potential of chromonyl-pyrimidines as therapeutics for TB is demonstrated.