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

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 over its parent glycinamide.

We describe the design, synthesis, and evaluation, of γ-lactams as glycinamide replacements within a series of di- and trisubstituted cyclohexane CCR2 antagonists.Figure optionsDownload as PowerPoint slide