| Autor: |
Soper DL; The Procter & Gamble Pharmaceuticals, Inc., Cincinnati, OH 45241, USA., Sheville JX, O'Neil SV, Wang Y, Laufersweiler MC, Oppong KA, Wos JA, Ellis CD, Baize MW, Chen JJ, Fancher AN, Lu W, Suchanek MK, Wang RL, Schwecke WP, Cruze CA, Buchalova M, Belkin M, Wireko F, Ritter A, De B, Wang D, Demuth TP Jr |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2006 Dec 01; Vol. 14 (23), pp. 7880-92. |
| DOI: |
10.1016/j.bmc.2006.07.056 |
| Abstrakt: |
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%). |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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