| Literature DB >> 16908171 |
David L Soper1, Justin X Sheville, Steven V O'Neil, Yili Wang, Michael C Laufersweiler, Kofi A Oppong, John A Wos, Christopher D Ellis, Mark W Baize, Jack J Chen, Amy N Fancher, Wei Lu, Maureen K Suchanek, Richard L Wang, William P Schwecke, Charles A Cruze, Maria Buchalova, Marina Belkin, Fred Wireko, Amanda Ritter, Biswanath De, Difei Wang, Thomas P Demuth.
Abstract
An 8,5-fused bicyclic peptidomimetic ring system generated by a stereoselective ring metathesis reaction was elaborated into potent inhibitors of interleukin-1beta converting enzyme (ICE, caspase-1). Multiple compounds were found that exhibited ICE IC50 values < 10 nM and were selective over caspase-3 and caspase-8. These active analogs generally possessed good activity (IC50 values < 100 nM) in a whole cell assay measuring IL-1beta production. Pharmacokinetic analysis of the ethyl acetal prodrug form of a selected active lead revealed a compound with a reasonable plasma half-life (1.1 h) and good oral bioavailability (30%).Entities:
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Year: 2006 PMID： 16908171 DOI： 10.1016/j.bmc.2006.07.056
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641