Solid-phase synthesis of the alkenyldiarylmethane (ADAM) series of non-nucleoside HIV-1 reverse transcriptase inhibitors

The Sonogashira and Stille cross-coupling reactions have been employed in t he synthesis of several non-nucleoside reverse transcriptase inhibitors (NN RTIs) in the alkenyldiarylmethane (ADAM) series. The synthesis has been car ried out both in solution and on a solid support. In contrast to previous s yntheses of NNRTIs in the ADAM series, the present strategy allows the inco rporation of differently substituted aromatic rings in a stereochemically d efined fashion. The most potent of the new ADAMs inhibited the cytopathic e ffect of HIV-1(RF) in CEM-SS cell culture with an EC50 value of 20 nM.