Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders

Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders

Structure–activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-in...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:ACS medicinal chemistry letters 2016-04, Vol.7 (4), p.397-402
Hauptverfasser: Xu, Heng, Lu, Hongfu, Xu, Zhongmiao, Luan, Linbo, Li, Chengyong, Xu, Yan, Dong, Kelly, Zhang, Jinqiang, Li, Xiong, Li, Yvonne, Liu, Gentao, Gong, Sophie, Zhao, Yong-Gang, Liu, Ailian, Zhang, Yueting, Zhang, Wei, Cai, Xin, Xiang, Jia-Ning, Elliott, John D, Lin, Xichen
Format: Artikel
Sprache:eng
Schlagworte:
Letter
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Structure–activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.5b00489