7-Substituted-[1,4]dioxano[2,3-g]quinazolines as inhibitors of epidermal growth factor receptor kinase.
With the aim of developing inhibitors of EGFR tyrosine kinase, the 7-methoxymethyl-[1,4]dioxano[2,3-g]quinazolines (3a-b) and 7-mono- or di-alkylaminomethyl-[1,4]dioxano[2,3-g]quinazolines (4a-i) were prepared and evaluated for the inhibition of EGFR tyrosine kinase and the growth inhibition of human tumor cell lines. Among them, compounds 4d and 4h showed potencies against both EGFR tyrosine and the A431 cell line similar to that of PD153035 with greater aqueous solubilities of their HCl salts.
Lee
Jae Yeol
JY
Medicinal Chemistry Research Center, Korea Institute of Science & Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Korea.
Park
Yong Kyu
YK
Seo
Seon Hee
SH
Yang
Beom-Seok
BS
Park
Hokoon
H
Lee
Yong Sup
YS
D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011799:Quinazolines; D066246:ErbB Receptors