Clive Gideon Diefenbacher

Potent non-peptidic dual inhibitors of endothelin-converting enzyme and neutral endopeptidase 24.11 ☆

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 IC50s of 17 and 5 nM, respectively.

Phosphonic acid analogs of diclofenac: an Arbuzov reaction of trimethylphosphite with an ortho-quinonoid intermediate

Abstract The phosphonic acid analog of the NSAID Diclofenac was efficiently synthesized via an Arbuzov reaction between 2-(2,6-dichloroanilino)benzyl alcohol and trimethyl phosphite followed by TMSBr promoted dealkylation. Seven related phosphonic acids were synthesized using the same novel acid-catalyzed Arbuzov reaction as the key step.