Synthesis and biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as potent EGFR inhibitors.
A series of C-6 or C-3' alkynyl-substituted 4-anilinoquinazoline derivatives was prepared straightforwardly by a Sonogashira reaction of the corresponding bromo-substituted 4-anilinoquinazolines. Bioactive assay of these compounds for in vitro EGFR kinase inhibition demonstrated that the novel 6-hydroxypropynyl-4-anilinoquinazoline 5e was a very potent EGFR kinase inhibitor with an IC(50) of 14 nM.
Liu
Lee Tai
LT
Development Center for Biotechnology, 102 Lane 169 Kang Ning Street, Xi Zhi, Taipei, Taiwan, ROC. letliu@yahoo.com.tw
Yuan
Ta-Tung
TT
Liu
Hung-Huang
HH
Chen
Shyh-Fong
SF
Wu
Ying-Ta
YT
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C527769:6-hydroxypropynyl-4-anilinoquinazoline; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors