Development of HIV protease inhibitors: A survey

Part of the Progress in Drug Research book series (PDR, volume 51)


In the treatment of infections caused by rapidly mutating viruses like human immunodeficiency virus (HIV), combination therapy with multiple drugs acting 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, hundreds 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 protease inhibitors as antiviral agents against HIV, and structure-activity relationship analysis of saquinavir and related compounds. Limitations of some protease inhibitors and ways to overcome the shortcomings are presented. Among these many protease inhibitors four have been marketed during 1995–1997. They are saquinavir, ritonavir, indinavir and nelfinavir. Their different structural features, important physicochemical, pharmacokinetic and clinical profiles are presented in a table form for easy comparison. It is hoped that in the future new drugs based on additional mechanisms can be developed for the treatment of AIDS.


AIDS antiviral agents chemotherapy HIV protease inhibitors indinavir nelfinavir ritonavir saquinavir structure-activity relationship 

Glossary of abbreviations


3-amino-2-hydroxy-4-phenylbutanoic acid


4-amino-3-hydroxy-5-phenylpentanoic acid


acquired immunodeficiency syndrome







Clog P

calculated partition coefficient in octanol water




cytochrome P450 3A4


two-fold rotational symmetry








human immunodeficiency virus

Log P

partition coefficient in octanol/water


molecular weight


nucleoside reverse transcriptase inhibitors




quinoline2- carbonyl


reverse transcriptase


structure-activity relationship










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Copyright information

© Springer Basel AG 1998

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, School of PharmacyUniversity of Southern CaliforniaLos AngelesUSA

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