Author/Authors :
Stéphane De Lombaert، نويسنده , , Lisa B. Stamford، نويسنده , , Louis Blanchard، نويسنده , , Jenny Tan، نويسنده , , Denton Hoyer، نويسنده , , Clive G. Diefenbacher، نويسنده , , Dongchu Wei، نويسنده , , Eli M. Wallace، نويسنده , , Michael A. Moskal، نويسنده , , Paula Savage، نويسنده , , Arco Y. Jeng، نويسنده ,
Abstract :
Structural modifications of CGS 26303, a non-peptidic α-aminophosphonate dual ECE/NEP inhibitor lead, were performed to maximize inhibition of recombinant human ECE-1, while maintaining strong NEP inhibition. Specifically, substitution of the α-aminophosphonate moiety with aryl ethyl side-chains led to the discovery of a new class of potent, non-peptidic, dual inhibitors, such as CGS 31447, which blocked ECE-1 and NEP activities with IC50ʹs of 17 and 5 nM, respectively.
