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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
.................................... ."
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