bS Supporting Information ABSTRACT: A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds were identified that exhibit comparable efficacy to marketed tetracyclines in in vivo models of bacterial infection. The tetracycline class of antibacterial agents has seen wide-spread clinical use for over 50 years due to its broad spectrum anti-bacterial activity.1 Tetracyclines inhibit bacterial growth by prevent-ing protein biosynthesis through binding to the 30S ribosome
