Synthesis and biological evaluation of benzamides and benzamidines: structural requirement of a pyrimidine ring for inhibition of EGFR tyrosine kinase.
The benzamides 1 and the benzamidines 2-3 were synthesized as the mimics of 4-anilinoquinazolines, which possess inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase, and tested for cytotoxicity toward A431 and inhibitory activity toward autophosphorylation by the enzyme assay. High cell growth inhibition was observed in a series of the cyclic benzamides 3: the IC(50) values are 0.09-0.32 mM. The benzamidines 3a and 3b exhibited high inhibition of EGFR tyrosine kinase at a 1.0 microM concentration, although the benzamides 1 and the benzamidines 2 did not show significant kinase inhibition at a 10 microM concentration.
Asano
Toru
T
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8588, Japan.
Yoshikawa
Tomohiro
T
Nakamura
Hiroyuki
H
Uehara
Yoshimasa
Y
Yamamoto
Yoshinori
Y
D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D001550:Benzamidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure
D001549:Benzamides; D001550:Benzamidines; D066246:ErbB Receptors