Non-peptidic inhibitors of neutral endopeptidase 24.11 1. Discovery and optimization of potency

Although based on a single α-amino acid residue, N-phosphonomethyl-(S)-(4-phenyl)phenylalanine (2) was discovered to produce strong inhibition of the zinc metalloprotease, neutral endopeptidase (NEP 24.11). Structural optimization of this new lead culminated with the design of the phosphonic acid tetrazole 17 (CGS 26303), a non-peptidic and extremely potent NEP inhibitor.