Abstract: Selective MMP-13 inhibitors are benzo thiadiazines of the Formula or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen or alkyl; R1 and R3 include hydrogen, alkyl, and aryl, with the proviso that R3 is not (CH2)m biphenyl or (CH2)m substituted biphenyl; X is O or NH, n is 0, 1, or 2. The compounds of Formula I, or a pharmaceutically acceptable salt thereof, is useful for treating diseases mediated by an MMP-13 enzyme, including diseases selected from osteoarthritis, rheumatoid arthritis, cancer, inflammation, and heart failure.