Synthesis, Structure-Activity Relationship and in Vivo Antiinflammatory Efficacy of Substituted Dipiperidines as CCR2 Antagonists

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• 作者：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 ; Mich
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 15, 2007
• 年：2007
• 卷：50
• 期：23
• 页码：5561 - 5563
• 全文大小：43K
• 年卷期：v.50,no.23(November 15, 2007)
• ISSN：1520-4804

文摘

A series of substituted dipiperidine compounds have beensynthesized and identified as selective CCR2 antagonists. Combiningthe most favorable substituents led to the discovery of remarkably potentCCR2 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 inadjuvant-induced arthritis model, collagen-induced arthritis model, andallergic asthma model.