The Synthesis Of Symmetrical And Unsymmetrical P1/P1 ' Cyclic Ureas As Hiv Protease Inhibitors

Cyclic urea SD146, a potent HIV protease inhibitor bearing a flat resistance profile, possessed poor solubility and bioavailability, which precluded further development of the compound. In an effort to improve upon the pharmacokinetic profile of the compound, several analogs modified at the P1/P1' residues were prepared and evaluated. Several of those compounds displayed significant improvement of physical properties. (C) 1998 The DuPont Merck Pharmaceutical Company. Published by Elsevier Science Ltd. All rights reserved.