Author/Authors :
Stephen W. Kaldor، نويسنده , , Bruce A. Dressman، نويسنده , , Marlys Hammond، نويسنده , , J Ernest Villafranca and Krzysztof Appelt، نويسنده , , Jeffrey A. Burgess، نويسنده , , Penny P. Lubbehusen، نويسنده , , Mark A. Muesing، نويسنده , , Steven D. Hatch، نويسنده , , Mary Ann Wiskerchen، نويسنده , , Angela J. Baxter، نويسنده ,
Abstract :
Using the X-ray crystal structure of the inhibitor 1 complexed to HIV-1 protease, a new series of HIV-1 protease inhibitors was developed incorporating substituted isophthalic acid derivatives as amino acid surrogates. Through iterative structure-based design, the lead compound 2 was optimized to produce a variety of non-peptide HIV-1 protease inhibitors with significant antiviral activity. In contrast to 1, several members of this series exhibit significant oral absorption in animals.
