| Abstract
| - Non-nucleoside inhibitors of HIV reverse transcriptase (NNRTIs), albeit not the mainstays of HIV/AIDStreatment, have become increasingly important in highly active antiretroviral therapy (HAART) due to theirunique mechanism of action. Several years ago our group identified the alkenyldiarylmethanes (ADAMs)as a potent and novel class of NNRTIs; however, the most active compounds were found to be metabolicallyunstable. Subsequent work has led to the synthesis of 33 analogues, with improved metabolic profiles,through the replacement of labile esters with various heterocycles, nitriles, and thioesters. As a result, anumber of hydrolytically stable NNRTIs were identified with anti-HIV activity in the nanomolar concentrationrange. Furthermore, an improved pharmacophore model has been developed based on the new ADAM series,in which a salicylic acid-derived aryl ring is oriented cis to the side chain and the aryl ring that is trans tothe side chain contains a hydrogen bond acceptor site within the plane of the ring.
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