Zhang Fengqi, Chapman Kevin T, Schleif William A, Olsen David B, Stahlhut Mark, Rutkowski Carrie A, Kuo Lawrence C, Jin Lixia, Lin Jiunn H, Emini Emilio A, Tata James R
Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Bioorg Med Chem Lett. 2003 Aug 4;13(15):2573-6. doi: 10.1016/s0960-894x(03)00474-8.
Replacement of the pyridylmethyl moiety in indinavir with a pyridyl oxazole yielded HIV-1 protease inhibitors (PI) with greatly improved potency against PI-resistant HIV-1 strains. A meta-methoxy group on the pyridyl ring and a gem-dimethyl methyl linkage afforded compound 10 with notable in vitro antiviral activity against HIV-1 viral strains with reduced susceptibility to the clinically available PIs. Compound 10 also demonstrated favorable in vivo pharmacokinetics in animal models.
