In the treatment of infections caused by rapidly mutating viruses like
human immunodeficiency virus (HIV), combination therapy with multiple
drugs act- ing by different mechanisms offers several advantages over
monotherapy. It may provide: synergistic effect, possible reduction of
dosages and side-effects, and reduction of the chance of drug
resistance. In the past few years, hun- dreds of HIV protease inhibitors
have been synthesized and tested in order to overcome the limitations of
reverse transcriptase inhibitors like zidovudine and others. In this
review, emphasis is placed on the development of HIV pro- tease
inhibitors as antiviral agents against HIY, and structure-activity rela-
tionship analysis of saquinavir and related compounds. Limitations of
some protease inhibitors and ways to overcome the shortcomings are
presented. Among these many protease inhibitors five have been marketed
during 1995-1999. They are saquinavir, ritonavir, indinavir, nelfinavir
and ampre- navir. Their different structural features, important
physicochemical, phar- macokinetic and clinical profiles are presented
in a table form for easy com- parison. It is hoped that in the future
new drugs based on additional mech- anisms can be developed for the
treatment of AIDS. Contents 4 1 Introduction
.................................................................... .
HIV protease as a target for chemotherapy
................................... . 2 5 Design of protease inhibitors
.................................................. . 3 5 Basis of
rational design of HIV protease inhibitors ........................... .
3.1 5 New development of HIV protease inhibitors
................................ . 6 3.2 HIV protease inhibitors on the
market ........................................ . 20 4 20 4.1 SAR of
saquinavir and related compounds .................................... .
