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Seven 2,6-disubstituted N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide series containing various amine moieties were designed and synthesized as new anti-TB agents. Many of them show excellent in vitro activity against both drug-sensitive MTB strain H37Rv and two MDR-MTB clinical isolates (MIC: < 0.002-0.030μg/mL). Compounds 2f, 5e and 5g display acceptable safety and pharmacokinetic profiles, opening a new direction for further development.