Design and effective synthesis of novel templates, 3,7-diphenyl-4-amino-thieno and furo-[3,2-c]pyridines as protein kinase inhibitors and in vitro evaluation targeting angiogenetic kinases.
A novel class of 3,7-diphenyl-4-amino-thieno and furo[3,2-c]pyridine has been designed based on pharmacophore models of ATP competitive kinase inhibitors. Versatile synthetic methods via double Suzuki coupling to explore SAR have been established and potent inhibitors against angiogenetic targets, VEGFR2, Tie-2, and EphB4, have been successfully discovered.
Miyazaki
Yasushi
Y
GlaxoSmithKline K.K., Tsukuba Research Laboratories, 43, Wadai, Tsukuba 300-4247, Ibaraki, Japan. yasushi.miyazaki@gsk.com
Nakano
Masato
M
Sato
Hideyuki
H
Truesdale
Anne T
AT
Stuart
J Darren
JD
Nartey
Eldridge N
EN
Hightower
Kendra E
KE
Kane-Carson
Laurie
L
D016475:3T3 Cells; D000255:Adenosine Triphosphate / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D001667:Binding, Competitive; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry*; D036224:Receptor, EphB4 / Q000037:antagonists & inhibitors; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D005663:Furans; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013876:Thiophenes; D000255:Adenosine Triphosphate; D036224:Receptor, EphB4; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2