Non-Peptide Protease Inhibitors as Novel AntiHIV Agents.

The human immunodeficiency virus has been shown to be the causative agent for acquired immunodeficiency syndrome (AIDS). The human immunodeficiency virus encodes for unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors act by preventing the formation of functional proteins from precursor proteins, which are vital for production of mature infectious viral particles. This review summarizes the data documenting the pharmacology and chemistry of non-peptide protease inhibitors that may be used as therapeutic agents against the human immunodeficiency virus infection. These agents are structural mimics of peptides with little or no peptidic character, thus overcoming various pharmacological problems of peptidic protease inhibitors. Structure-based drug designs of potent protease inhibitors, discovered through broad screening, have been developed into various clinical candidates for the treatment of AIDS. Non-peptide protease inhibitors could provide a useful model in the further search for novel compounds with even more pertinent pharmacological and pharmacokinetic profiles. [ABSTRACT FROM AUTHOR]