This is why the medication is not recommended for patients with a history of pulmonary edema with the usage of ACE inhibitors.

[4] In addition, neprilysin degrades a variety of peptides including bradykinin,[5] an inflammatory mediator.

The large scale synthesis of sacubritil begins with 4-bromo-1,1'-biphenyl, which is converted to its corresponding Grignard reagent; this is reacted directly with (S)-epichlorohydrin regioselectively at less-substituted site of the epoxide.

Asymmetric hydrogenation using a ruthenium catalyst and a chiral bisphosphine ligand sets the second stereocenter.

The acidic conditions under which the acyl chloride is generated result in removal of the Boc group, which allows for direct reaction of the amine with succinic anhydride in the presence of pyridine as a base.