Potent cyclic urea HIV protease inhibitors with benzofused heterocycles as P2/P2' groups

Article abstract of DOI:10.1016/S0960-894X(96)00531-8

A series of benzofused heterocycles was examined to replace the metabolically unstable benzyl alcohol P2/P2' groups of DMP 323 (1). Extremely potent inhibitors of HIV protease (Ki < 0.01 nM) and excellent antiviral activity (IC₉₀ = 8 nM) were found. An X-ray crystal structure of benzimidazolone 5a bound to HIV protease showed H-bonds to Asp30 and a bridging water molecule to Gly48.