POTENT AND SELECTIVE SEMICARBAZIDE-SENSITIVE AMINE OXIDASE (SSAO) INHIBITORS WITH ANTI-INFLAMMATORY ACTIVITIES

Eric Y. Wang, Hongfeng Gao, Mary MacDonald, David Jones, Huong-Thu Ton-Nu, Anne O’Rourke, Luisa Salter-Cid, Li Huang, Andrew Miller, and Matthew D. Linnik, La Jolla Pharmaceutical Company

Abstract

Semicarbazide-sensitive amine oxidase (SSAO, EC1.4.3.6, also known as vascular adhesion molecule-1, VAP-1) is a copper-containing amine oxidase that has both enzymatic and adhesive function. SSAO catalyzes the oxidative deamination of primary amines, which results in the formation of the corresponding aldehydes, hydrogen peroxide, and ammonia. Membrane-bound SSAO is an inflammation-inducible endothelial cell adhesion molecule that mediates the interaction between leukocytes and activated endothelial cells in inflamed vessels. Recent studies have suggested that the inhibition of human SSAO could have therapeutic benefits in the area of inflammatory diseases. We have discovered a series of benzyl amine derivatives that are potent and selective SSAO inhibitors. Discussion of SAR, ADME data, and relevant in vivo biological results will be presented.

Presented at the
ACS National Meeting in San Francisco
September 10-14, 2006