Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing

Li Zhengnian; Powell Chelsea E.; Groendyke Brian J.Gero Thomas W.Feru FredericFeutrill JohnChen BailingLi BinSzabo HilaryGray Nathanael S.Scott David A.

首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing

【24h】

Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing

机译：Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing

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

The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on our previous TNK2 inhibitor XMD8-87 identified urea 17 from which we developed the potent and selective compound 32. A co-crystal structure was obtained showing 32 interacting primarily with the main chain atoms of an alanine residue of the hinge region. Additional H-bonds exist between the urea NHs and the Thr205 and Asp270 residues.

著录项

来源
《Bioorganic and Medicinal Chemistry Letters》 |2020年第19期|共6页
作者
Li Zhengnian; Powell Chelsea E.; Groendyke Brian J.Gero Thomas W.Feru FredericFeutrill JohnChen BailingLi BinSzabo HilaryGray Nathanael S.Scott David A.;
展开▼
作者单位

Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA;

SYNth Med Chem, 425 Changyang St,Suzhou Ind Pk, Suzhou, Jiangsu, Peoples R China;

Vivid BioSci, 50 Northern Ave, Boston, MA 02210 USA;

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
TNK2; Kinase inhibitor; Benzopyrimidodiazepinone; Scaffold morphing;

Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing

摘要

著录项

相关主题

期刊订阅