title: Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea Derivatives as Potential EGFR Inhibitors.
abstract: Two novel series of diaryl urea derivatives5a-iand13a-lwere synthesized and evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231 cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives5a-idemonstrated significant activity, and seven of them are more active than sorafenib, with IC50values ranging from 0.089 to 5.46 μM. Especially, compound5aexhibited the most active potency both in cellular (IC50= 0.15, 0.089, 0.36, and 0.75 μM, respectively) and enzymatic assay (IC50= 56 nM against EGFR), representing a promising lead for further optimization.
authors.affiliation: Key Lab. of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. jiangnan@syphu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Key Lab. of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. yanxinbu@163.com.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Key Lab. of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. wangyubobby@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Lab. of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. 18604019493@163.com.
authors.forename: Minhua
authors.initials: M
authors.lastname: Nie
authors.affiliation: Department of Chemsitry, Shenyang Medical College, 146 Huanghe North Street, Huanggu District, Shenyang 110034, China. zhangdajun2008@126.com.
authors.forename: Dajun
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Lab. of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. leixinjia@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D014508:Urea; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: 4-aminoquinazolinyl; EGFR inhibitors; cytotoxicity; diaryl urea; synthesis