Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors.

Abstract Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2′ subsite within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f , a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported.