title: Synthesis and p38 Inhibitory Activity of Some Novel Substituted N,N'-Diarylurea Derivatives.
abstract: We have identified a novel series of substituted N,N'-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were tested. Among these compounds, 25a inhibited the p38α enzyme with an IC50 value of 0.47 nM and a KD value of 1.54 × 10(-8) and appears to be the most promising one in the series.
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. zhudianxi@126.com.|Laboratory of Computer-Aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Rd., Beijing 100850, China. zhudianxi@126.com.
authors.forename: Dianxi
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Laboratory of Computer-Aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Rd., Beijing 100850, China. xingqf5522@163.com.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Laboratory of Computer-Aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Rd., Beijing 100850, China. 21cc@163.com.
authors.forename: Ruiyuan
authors.initials: R
authors.lastname: Cao
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. dongmeiz-67@163.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Laboratory of Computer-Aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Rd., Beijing 100850, China. zhongwu@bmi.ac.cn.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhong
mesh_terms: D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry; D014508:Urea / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D014508:Urea; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
keywords: BIRB-796; P38 MAPK; SPR; TNF-α