Optimization of a series of potent, selective and orally bioavailable SYK inhibitors

Grimster Neil P.; Gingipalli Lakshmaiah; Barlaam BernardSu QibinZheng XiaoLanWatson DavidWang HaixiaSimpson IainPike AndyBalazs AmberBoiko ScottIkeda Timothy P.Impastato Anna C.Jones Natalie H.Kawatkar SameerKemmitt PaulLamont ScottPatel JoeRead JonSarkar UjjalSha LiTomlinson Ronald C.Wang HaiyunWilson David M.Zehnder Troy E.Wang LiangheWang PengGoldberg Frederick W.Shao WenlinFawell StephenDry HannahDowling James E.Edmondson Scott D.

首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Optimization of a series of potent, selective and orally bioavailable SYK inhibitors

【24h】

Optimization of a series of potent, selective and orally bioavailable SYK inhibitors

机译：Optimization of a series of potent, selective and orally bioavailable SYK inhibitors

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Spleen tyrosine kinase (SYK) is a non-receptor cytosolic kinase. Due to its pivotal role in B cell receptor and Fcreceptor signaling, inhibition of SYK has been targeted in a variety of disease areas. Herein, we report the optimization of a series of potent and selective SYK inhibitors, focusing on improving metabolic stability, pharmacokinetics and hERG inhibition. As a result, we identified 30, which exhibited no hERG activity but unfortunately was poorly absorbed in rats and mice. We also identified a SYK chemical probe, 17, which exhibits excellent potency at SYK, and an adequate rodent PK profile to support in vivo efficacy/PD studies.

著录项

来源
《Bioorganic and Medicinal Chemistry Letters》 |2020年第19期|共7页
作者
Grimster Neil P.; Gingipalli Lakshmaiah; Barlaam BernardSu QibinZheng XiaoLanWatson DavidWang HaixiaSimpson IainPike AndyBalazs AmberBoiko ScottIkeda Timothy P.Impastato Anna C.Jones Natalie H.Kawatkar SameerKemmitt PaulLamont ScottPatel JoeRead JonSarkar UjjalSha LiTomlinson Ronald C.Wang HaiyunWilson David M.Zehnder Troy E.Wang LiangheWang PengGoldberg Frederick W.Shao WenlinFawell StephenDry HannahDowling James E.Edmondson Scott D.;
展开▼
作者单位

AstraZeneca, Oncol R&D, Waltham, MA 02451 USA;

AstraZeneca, Oncol R&D, Cambridge, England;

AstraZeneca, Discovery Sci, R&D, Waltham, MA USAAstraZeneca, Discovery Sci, R&D, Cambridge, EnglandPharmaron Beijing Co Ltd, 6 Taihe Rd BDA, Beijing 100176, Peoples R China;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类药学;
关键词
SYK; Bioavailable; Small molecule;

Optimization of a series of potent, selective and orally bioavailable SYK inhibitors

摘要

著录项

相关主题

期刊订阅