Synthesis, Structure−Activity Relationship and in Vivo Antiinflammatory Efficacy of Substituted Dipiperidines as CCR2 Antagonists
journal contributionposted on 2007-11-15, 00:00 authored by Mingde Xia, Cuifen Hou, Duane E. DeMong, Scott R. Pollack, Meng Pan, James A. Brackley, Nareshkumar Jain, Chrissy Gerchak, Monica Singer, Ravi Malaviya, Michele Matheis, Gil Olini, Druie Cavender, Michael Wachter
A series of substituted dipiperidine compounds have been synthesized and identified as selective CCR2 antagonists. Combining the most favorable substituents led to the discovery of remarkably potent CCR2 antagonists displaying IC50 values in the nanomolar range. Compound 7a had outstanding selectivity over CCR1, CCR3, CCR4, CCR5, CCR6, CCR7, and CCR8 and showed excellent efficacy in adjuvant-induced arthritis model, collagen-induced arthritis model, and allergic asthma model.