| Literature DB >> 27096048 |
Heng Xu1, Hongfu Lu2, Zhongmiao Xu2, Linbo Luan2, Chengyong Li2, Yan Xu2, Kelly Dong2, Jinqiang Zhang2, Xiong Li2, Yvonne Li2, Gentao Liu2, Sophie Gong2, Yong-Gang Zhao2, Ailian Liu2, Yueting Zhang2, Wei Zhang2, Xin Cai2, Jia-Ning Xiang2, John D Elliott2, Xichen Lin2.
Abstract
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.Entities:
Keywords: CNS penetration; CXCR2 antagonists; cuprizone model; demyelinating disorders; demyelination and remyelination; diarylureas; multiple sclerosis
Year: 2016 PMID： 27096048 PMCID： PMC4834652 DOI： 10.1021/acsmedchemlett.5b00489
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345