Synthesis and evaluation of novel 8,6-fused bicyclic peptidomimetic compounds as interleukin-1β converting enzyme inhibitors

Two novel 8,6-fused bicyclic peptidomimetic ring systems were synthesized utilizing olefin metathesis as the key reaction for the formation of the eight-membered ring. Both peptidomimetic scaffolds were further elaborated into potent ICE inhibitors, with numerous compounds exhibiting caspase-1 IC50s less than 10 nM.

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