title: Synthesis and inhibitory activity of 4-alkynyl and 4-alkenylquinazolines: identification of new scaffolds for potent EGFR tyrosine kinase inhibitors.
abstract: The present study identified several 4-alkynyl and 4-alkenylquinazolines that serve as novel and potent EGFR tyrosine kinase inhibitors. The IC(50) values of these compounds are in the nanomolar range. In addition, the 4-(4-phenylbut-1-yn/en-yl)quinazolines provided scaffolds for potent enzyme inhibition. Chiral discrimination was observed to occur in one of the 4-alkynylquinazoline derivatives with the (R)-isomer being more than 150 times as potent as the (S)-isomer.
authors.affiliation: Mitsubishi Pharma Corporation, Pharmaceuticals Research Division, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Kitano.Yasunori@mc.mt-pharma.co.jp
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kitano
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawahara
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamazaki
mesh_terms: D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors