ORGN 278 |
| Activation of the complement system plays a role in the normal inflammatory and immune response. In response to certain stimuli a proteolytic cascade is initiated, resulting in formation of bioactive peptides including C5a. This peptide binds to a specific G-protein coupled receptor (C5aR) on target cells (neutrophils, monocytes, macrophages, and others), recruiting them to sites of inflammation and stimulating release of additional pro-inflammatory mediators. Antagonists of C5aR are sought as potential therapeutic agents for autoimmune and inflammatory conditions involving over-activation of the complement system. The discovery, synthesis, and optimization of a series of non-peptidic, small molecule C5aR antagonists will be disclosed. Data pertaining to antagonism of C5a binding and functional activity, early ADME properties, rat pharmacokinetics, and species selectivity of the compounds will be presented. |
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Young Industrial Investigators
9:00 AM-12:05 PM, Monday, August 20, 2007 BCEC -- Ballroom, Oral
Division of Organic Chemistry |