Discovery and synthesis of cyclohexenyl derivatives as modulators of CC chemokine receptor 2 activity

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• 作者：Gregory D. Brown ; ^{gregory.brown@bms.com" class="auth_mail" title="E-mail the corresponding author} ; Qing Shi ; George V. Delucca ; Douglas G. Batt ; Michael A. Galella ; Mary-Ellen Cvijic ; Rui-Qin Liu ; Feng Qiu ; Qihong Zhao ; Joel C. Barrish ; Percy H. Carter
• 关键词：Chemokine ; CCR2 ; CCR2 antagonist ; GPCR
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：26
• 期：2
• 页码：662-666
• 全文大小：1165 K

文摘

A novel cyclohexenyl series of CCR2 antagonists has been discovered. This series of small, rigid compounds exhibits submicromolar binding affinity for CCR2. Modification of the substituents on the cyclohexene ring led to the identification of potent CCR2 antagonists. Progress from initial lead 5 (IC₅₀ = 700 nM) to (−)-38 (IC₅₀ = 9.0 nM) is discussed.