Discovery of dihydroquinoxalinone acetamides containing bicyclic amines as potent Bradykinin B1 receptor antagonists

doi:10.1016/j.bmcl.2008.07.055

Bioorganic & Medicinal Chemistry Letters

Volume 18, Issue 16, 15 August 2008, Pages 4477-4481

https://doi.org/10.1016/j.bmcl.2008.07.055 Get rights and content

Abstract

Replacement of the core β-amino acid in our previously reported piperidine acetic acid and β-phenylalanine-based Bradykinin B1 antagonists by dihydroquinoxalinone acetic acid increases the in vitro potency and metabolic stability. The most potent compounds from this series have IC₅₀s < 0.2 nM in a human B1 receptor functional assay. A molecular modeling study of the binding modes of key compounds, based on a B1 homology model, explains the structure–activity relationship (SAR) for these analogs.

Graphical abstract

Novel dihydroquinoxalinone acetamides containing bicyclic aminotetralins or chromans were found to be potent Bradykinin B1 receptor antagonists.

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Discovery of dihydroquinoxalinone acetamides containing bicyclic amines as potent Bradykinin B1 receptor antagonists

Abstract

Graphical abstract

Trends Pharmacol. Sci.

Bioorg. Med. Chem. Lett.

Biochem. Biophys. Res. Commun.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem. Lett.

Br. J. Pharmacol.

Nat. Rev.

Expert Opin. Ther. Targets

J. Med. Chem.