title: Synthesis and biological evaluation of benzamides and benzamidines: structural requirement of a pyrimidine ring for inhibition of EGFR tyrosine kinase.
abstract: 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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8588, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Asano
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Uehara
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: 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
chemical_list: D001549:Benzamides; D001550:Benzamidines; D066246:ErbB Receptors