Bradykinin B1 receptor antagonists: An α-hydroxy amide with an improved metabolism profile

A series of carbo- and heterocyclic α-hydroxy amide-derived bradykinin B1 antagonists was prepared and evaluated. A 4,4-difluorocyclohexyl α-hydroxy amide was incorporated along with a 2-methyl tetrazole in lieu of an oxadiazole to afford a suitable compound with good pharmacokinetic properties, CNS penetration, and clearance by multiple metabolic pathways.

Graphical abstractThe design and synthesis of human bradykinin B1 antagonists featuring N-methyl tetrazole and α-hydroxy amide moieties are disclosed.Figure optionsDownload full-size imageDownload as PowerPoint slide