title: Design, synthesis and biological evaluation of novel pyrimidine, 3-cyanopyridine and m-amino-N-phenylbenzamide based monocyclic EGFR tyrosine kinase inhibitors.
abstract: 36 new compounds with the typical skeleton of 4-anilino-5-vinyl/ethynyl pyrimidine, 4-anilino-3-cyano-5-vinyl/ethynyl/phenyl pyridine, and m-amino-N-phenylbenzamide, are designed, synthesized and selectively tested on EGFR, ErbB-2 kinases, and A-549, HL60 cells growth inhibition. Results from the bioactivity and chemical structures yield preliminary structure-activity relationships (SARs). The most potent 5-ethynylpyrimidine derivative 20a has an IC50 value of 45 nM to EGFR kinase. Several compounds of other series also show IC50 values <1 μM for EGFR and <5 μM for A-549 and HL60 cells growth inhibition.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Pudong, Shanghai 201203, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Mao
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Zhu
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Kong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Nicholas Kenneth
authors.initials: NK
authors.lastname: Terrett
authors.forename: Jingkang
authors.initials: J
authors.lastname: Shen
authors.forename: Jingshan
authors.initials: J
authors.lastname: Shen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D066246:ErbB Receptors; D011725:Pyridines; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human