Pyridinylimidazole inhibitors of Tie2 kinase.
This communication details the evolution of the screening lead SB-203580, a known CSBP/p38 kinase inhibitor, into a potent and selective Tie2 tyrosine kinase inhibitor. The optimized compound 5 showed efficacy in an in vivo model of angiogenesis and a MOPC-315 plasmacytoma xenograft model.
Semones
Marcus
M
GlaxoSmithKline, Collegeville, PA 19426, USA. marcus.a.semones@gsk.com
Feng
Yanhong
Y
Johnson
Neil
N
Adams
Jerry L
JL
Winkler
Jim
J
Hansbury
Michael
M
D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D009368:Neoplasm Transplantation; D010954:Plasmacytoma / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D042787:Receptor, TIE-2; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580