Author/Authors :
Fengqi Zhang، نويسنده , , Kevin T. Chapman، نويسنده , , William A. Schleif، نويسنده , , David B. Olsen، نويسنده , , Mark Stahlhut، نويسنده , , Carrie A. Rutkowski، نويسنده , , Lawrence C. Kuo، نويسنده , , Lixia Jin، نويسنده , , Jiunn H. Lin، نويسنده , , Emilio A. Emini، نويسنده , , James R. Tata، نويسنده ,
Abstract :
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.
