γ-Lactams as glycinamide replacements in cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists

…, YC Lo, G Yang, PB Miller, PA Scherle, Q Zhao…

Index: Cherney, Robert J.; Mo, Ruowei; Meyer, Dayton T.; Voss, Matthew E.; Yang, Michael G.; Santella III, Joseph B.; Duncia, John V.; Lo, Yvonne C.; Yang, Gengjie; Miller, Persymphonie B.; Scherle, Peggy A.; Zhao, Qihong; Mandlekar, Sandhya; Cvijic, Mary Ellen; Barrish, Joel C.; Decicco, Carl P.; Carter, Percy H. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 8 p. 2425 - 2430

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Citation Number: 14

Abstract

We describe the design, synthesis, and evaluation, of γ-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 IC50= 1.0 nM and chemotaxis IC50= 0.5 nM) and improved metabolic stability ...