Author/Authors :
Michael C. Laufersweiler، نويسنده , , Yili Wang، نويسنده , , David L. Soper، نويسنده , , Maureen K. Suchanek، نويسنده , , Amy N. Fancher، نويسنده , , Wei Lu، نويسنده , , Richard L. Wang، نويسنده , , Kofi A. Oppong، نويسنده , , Christopher D. Ellis، نويسنده , , Mark W. Baize، نويسنده , , Steven V. O’Neil، نويسنده , , John A. Wos، نويسنده , , Thomas P. Demuth Jr.، نويسنده ,
Abstract :
The application of a tricyclic pyrrolopyrimidinone scaffold for the synthesis of peptidomimetic inhibitors of interleukin-1β-converting enzyme (ICE) is reported. The synthesis of the tricyclic scaffold and conversion of it to a variety of target ICE inhibitors were accomplished in 4–5 steps. In vitro biological evaluation of the tricyclic pyrrolopyrimidinones revealed fair to good ICE inhibitors, with the most active compound exhibiting an IC50 of 14 nM in a caspase-1 enzyme binding assay.
Keywords :
Pyrrolopyrimidinones , Caspase-1 , Heterocycles , Interleukin-1?-converting enzyme , Peptidomimitics
