Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease

被引：20

作者：

Barker, Michael D. ^{[1
]}

Liddle, John ^{[1
]}

Atkinson, Francis L. ^{[1
,2
]}

Wilson, David Matthew ^{[1
,3
]}

Dickson, Marion C. ^{[1
]}

Ramirez-Molina, Cesar ^{[1
]}

Lewis, Huw ^{[1
]}

Davis, Rob P. ^{[1
]}

Somers, Donald O. ^{[1
]}

Neu, Margarete ^{[1
]}

Jones, Emma ^{[1
]}

Watson, Robert ^{[1
]}

机构：

[1] GlaxoSmithKline R&D, Med Res Ctr, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England

[2] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England

[3] AstraZeneca, IMED Biotech Unit, Darwin Bldg, Cambridge CB4 0WG, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2018年 / 28卷 / 21期

关键词：

SYK; Spleen Tyrosine Kinase; Lead optimisation; Inhibitor; Skin penetration; Dermal; RHEUMATOID-ARTHRITIS; SYK INHIBITOR;

D O I：

10.1016/j.bmcl.2018.09.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and lead optimisation of a novel series of SYK inhibitors is described. These were optimised for SYK potency and selectivity against Aurora B. Compounds were profiled in a human skin penetration study to identify a suitable candidate molecule for pre-clinical development. Compound 44 (GSK2646264) was selected for progression and is currently in Phase I clinical trials.

引用

页码：3458 / 3462

页数：5

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