Synthesis and inhibitory activity of 4-alkynyl and 4-alkenylquinazolines: identification of new scaffolds for potent EGFR tyrosine kinase inhibitors.
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.
Kitano
Yasunori
Y
Mitsubishi Pharma Corporation, Pharmaceuticals Research Division, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Kitano.Yasunori@mc.mt-pharma.co.jp
Suzuki
Tsuyoshi
T
Kawahara
Eiji
E
Yamazaki
Takahisa
T
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*
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors