Design, Synthesis and Biological Evaluation of Novel Substituted N,N'-Diaryl ureas as Potent p38 Inhibitors

Dianxi Zhu; Xingzhou Li; Wu Zhong; Dongmei Zhao

doi:10.3390/molecules200916604

Design, Synthesis and Biological Evaluation of Novel Substituted N,N'-Diaryl ureas as Potent p38 Inhibitors

Molecules. 2015 Sep 11;20(9):16604-19. doi: 10.3390/molecules200916604.

Authors

Dianxi Zhu¹, Xingzhou Li², Wu Zhong³, Dongmei Zhao⁴

Affiliations

¹ Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. [email protected].
² Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. [email protected].
³ Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China. [email protected].
⁴ Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. [email protected].

Abstract

A novel series of substituted N,N'-diaryl ureas that act as p38α inhibitors have been designed and synthesized based on two key residues (Gly110 and Thr106) that are different in p38α MAPK than in other kinases. Preliminary biological evaluation indicated that most compounds possessed good p38α inhibitory potencies. Among these compounds, 9g appeared to be the most powerful and is the main compound that we will study in the future.

Keywords: TNF-α; glycine flip; kinase inhibitor; p38 MAPK; p38 inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Urea / chemistry*
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

Protein Kinase Inhibitors
Urea
p38 Mitogen-Activated Protein Kinases