Design, synthesis, and conformational analysis of a novel series of HIV protease inhibitors

A combination of structure-based design and both solution, and solid-phase synthesis were utilized to derive a potent (nM) series of HIV-1 protease in hibitors bearing a structurally novel backbone. Detailed structural analysi s of several inhibitors prepared in this series has suggested that rigidifi cation of the P-1/P-2 region of this class of molecules may result in compo unds with improved potency. (C) 1998 Elsevier Science Ltd. All rights reser ved.