Renin inhibitors containing alpha-heteroatom amino acids as P2 residues.

Basic Information

ID: ALA1126322

Journal: J Med Chem

Title: Renin inhibitors containing alpha-heteroatom amino acids as P2 residues.

Authors: Repine JT, Kaltenbronn JS, Doherty AM, Hamby JM, Himmelsbach RJ, Kornberg BE, Taylor MD, Lunney EA, Humblet C, Rapundalo ST.

Abstract: A series of renin inhibitors having alpha-heteroatom amino acids as P2 substitutions has been prepared. Examples where the heteroatom is oxygen, sulfur, or nitrogen are described. Many of the compounds exhibit subnanomolar potency when tested in vitro against monkey renin. When selected compounds were tested orally in conscious, salt-depleted, normotensive, Cynomolgus monkeys, low to moderate blood pressure lowering was observed. At an oral dose of 30 mg/kg, compound 53a lowered blood pressure by a maximum of 18 mmHg at 2.5 h post-dose.

CiteXplore: 1552498

DOI: 10.1021/jm00084a008

Patent ID: