Michael Garret Roepel

Discovery and optimization of pyridazinone non-nucleoside inhibitors of HIV-1 reverse transcriptase.

A series of benzyl pyridazinones were evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Several members of this series showed good activity against the wild-type virus and NNRTI-resistant viruses. The binding of inhibitor 5a to HIV-RT was analyzed by surface plasmon resonance spectroscopy. Pharmacokinetic studies of 5a in rat and dog demonstrated that this compound has good oral bioavailability in animal species. The crystal structure of a complex between HIV-RT and inhibitor 4c is also described.

A one-pot radical addition/fragmentation route to ketones and esters

Abstract A simple one-pot procedure has been developed that combines carboncarbon bond formation via a radical addition to either substituted enol ethers or ketene acetals, with a subsequent fragmentation reaction to yield ketones and esters. The ‘masked’ methyl carbonyl radical acceptors discovered in this work are either commercially available or easily prepared in one to two steps.