Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Abstract

Various non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been reported to specifically inhibit human immunodeficiency virus type 1 (HIV-1): for example, tetrahydroimidazobenzodiazepinone (TIBO), hydroxyethoxymethylphenylthiothymine (HEPT), dipyridodiazepinone (i.e. nevirapine), pyridinone, bis(heteroaryl)piperazine (BHAP), tert-butyldimethylsilylspiroaminooxathioledioxide (TSAO), α-anilinophenylacetamide (α-APA) and quinoxaline derivatives. These compounds interact allosterically (i.e. non-competitively with respect to the natural substrate (dNTPs)) with a specific non-substrate binding site ‘pocket’ of the HIV-1 reverse transcriptase (RT). The most potent NNRTIs have been found to inhibit HIV-1 replication at nanomolar concentrations. These compounds therefore offer great potential for the treatment of HIV-1 infections. Yet, the virus may rapidly develop resistance to these drugs. The mutations conferring resistance have been mapped at the RT positions 100 (Leu × lle), 103 (Lys × Asn), 106 (...