Identification of Pyrazolo[1,5-<i>a</i>]pyridine-3-carboxamide Diaryl Derivatives as Drug Resistant Antituberculosis Agents

A series of pyrazolo[1,5- a ]pyridine-3-carboxamide (PPA) derivatives bearing diaryl side chain was designed and synthesized as new antituberculosis agents, aiming to improve the efficacy toward drug resistant Mycobacterium tuberculosis ( Mtb ) strains. Most of the substituted diphenyl and heterodiaryl PPAs exhibited excellent in vitro potency against the drug susceptive H37Rv strain (MIC Mtb strains (INH-resistant (rINH), MIC 6j displayed good pharmacokinetic profiles with oral bioavailability (F) of 41% and significantly reduced the bacterial burden in an autoluminescent H37Ra infected mouse model.