Nonpeptidic Inhibitors Op Neutral Endopeptidase-24.11 .2. Design And Pharmacology Of Orally-Active Phosphonate Prodrugs

Prodrugs of 1 (CGS 26303), a novel non-peptidic neutral endopeptidase (NEP 24.11) inhibitor, have been designed. In particular, the diphenylphosphonate 6 (CGS 26393) was found to be a potent, orally bioavailable and long-acting NEP inhibitor. Accordingly, 6 protected atrial natriuretic peptide from enzymatic degradation and displayed a significant antihypertensive activity in the DOCA-salt rat.