Antiviral activity of 4-benzyl pyridinone derivatives as HIV-1 reverse transcriptase inhibitors.

ABSTRACT

In this overview, the antiviral properties of the Curie-pyridinone compounds, a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) developed as anti-HIV agents, are described. These compounds are hybrids between hydroxyethoxymethyl-phenylthiothymine (HEPT) and Merck pyridinones. Several structure-activity relationships (SAR) studies between HIV-1 reverse transcriptase (RT) and the Curie-pyridinones are described. The Curie-pyridinones are potent inhibitors of both HIV-1 replication in cell culture and of HIV-1 RT activity in vitro. They are specific to HIV-1 and do not inhibit the replication of HIV-2. The mechanism of inhibition is non-competitive with respect to the natural substrate dGTP. For these reasons, the Curie-pyridinones can be considered as non-nucleoside inhibitors of HIV-1 RT. Moreover, they have the unusual ability to reach the reverse transcription complex inside the extracellular virions and may therefore be useful as retrovirucides. This might lead to the design and synthesis of new drugs able to interact with the retroviral enzyme inside the viral core.