CCR2 Small Molecule Antagonists

The in vivo efficacy seen with anti-MCP-1 antibodies and peptide antagonists prompts the search for small molecule CCR2 antagonists. The spiropiperidines (18-20) are early examples of CCR2 antagonists, as determined by 125I-MCP-1 binding and chemotaxisin THP-1 cells (110).As noted above with the CCR1 antagonists, a basic nitrogen is a common feature within this class of antagonists. Site-di-mutagenesis suggests that this nitrogen may form a critical recognition with an anionic residue (E291) in helix 7. The orthogonal relationship imposed on the phenyurethane and the piperidine ring by the spiro-carbon is urported to be essential for activity.

Selectivity is an issue for the spiropiperi-dines, given that this class of compounds shows appreciable activity against alpha adrenergic and 5-hydroxytiyptamine (5-HT) receptors. Although lead optimization improved CCR2 affinity (18) versus (20), and improved the relative difference in selectivity, the most


Was this article helpful?

0 0
Dealing With Asthma Naturally

Dealing With Asthma Naturally

Do You Suffer From ASTHMA Chronic asthma is a paralyzing, suffocating and socially isolating condition that can cause anxiety that can trigger even more attacks. Before you know it you are caught in a vicious cycle Put an end to the dependence on inhalers, buying expensive prescription drugs and avoidance of allergenic situations and animals. Get control of your life again and Deal With Asthma Naturally

Get My Free Ebook

Post a comment