Author/Authors :
Cynthia A. Fink، نويسنده , , Michael Moskal، نويسنده , , Fariborz Firooznia، نويسنده , , Denton Hoyer، نويسنده , , David Symonsbergen، نويسنده , , Dongchu Wei، نويسنده , , Ying Qiao، نويسنده , , Paula Savage، نويسنده , , Michael E. Beil، نويسنده , , Angelo J. Trapani، نويسنده , , Arco Y. Jeng، نويسنده ,
Abstract :
Through directed screening of compounds prepared as metalloprotease inhibitors a compound, CGS 30084, that had potent endothelin converting enzyme-1 (ECE-1) in vitro inhibitory activity (IC50=77 nM) was identified. Herein we report the synthesis and optimization of ECE-1 inhibitory activity of additional analogues from this lead. Compound 3c, the thioacetate methyl ester derivative of compound 4c, was found to be a long acting inhibitor of ECE-1 activity in rats after oral administration.
