- gamma-Lactams as glycinamide replacements in cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists.
gamma-Lactams as glycinamide replacements in cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists.
Bioorganic & medicinal chemistry letters (2010-03-30)
Robert J Cherney, Ruowei Mo, Dayton T Meyer, Matthew E Voss, Michael G Yang, Joseph B Santella, John V Duncia, Yvonne C Lo, Gengjie Yang, Persymphonie B Miller, Peggy A Scherle, Qihong Zhao, Sandhya Mandlekar, Mary Ellen Cvijic, Joel C Barrish, Carl P Decicco, Percy H Carter
PMID20346664
RÉSUMÉ
We describe the design, synthesis, and evaluation, of gamma-lactams as glycinamide replacements within a series of di- and trisubstituted cyclohexane CCR2 antagonists. The lactam-containing trisubstituted cyclohexanes proved to be more potent than the disubstituted analogs, as trisubstituted analog, lactam 13, displayed excellent activity (CCR2 binding IC(50)=1.0 nM and chemotaxis IC(50) = 0.5 nM) and improved metabolic stability over its parent glycinamide.