603300-96-5Relevant academic research and scientific papers
Novel 6-aminofuro[3,2-c]pyridines as potent, orally efficacious inhibitors of cMET and RON kinases
Steinig, Arno G.,Li, An-Hu,Wang, Jing,Chen, Xin,Dong, Hanqing,Ferraro, Caterina,Jin, Meizhong,Kadalbajoo, Mridula,Kleinberg, Andrew,Stolz, Kathryn M.,Tavares-Greco, Paula A.,Wang, Ti,Albertella, Mark R.,Peng, Yue,Crew, Linda,Kahler, Jennifer,Kan, Julie,Schulz, Ryan,Cooke, Andy,Bittner, Mark,Turton, Roy W.,Franklin, Maryland,Gokhale, Prafulla,Landfair, Darla,Mantis, Christine,Workman, Jen,Wild, Robert,Pachter, Jonathan,Epstein, David,Mulvihill, Mark J.
, p. 4381 - 4387 (2013/07/26)
A series of novel 6-aminofuro[3,2-c]pyridines as kinase inhibitors is described, most notably, OSI-296 (6). We discuss our exploration of structure-activity relationships and optimization leading to OSI-296 and disclose its pharmacological activity against cMET and RON in cellular assays. OSI-296 is a potent and selective inhibitor of cMET and RON kinases that shows in vivo efficacy in tumor xenografts models upon oral dosing and is well tolerated.
The development of potent and selective bisarylmaleimide GSK3 inhibitors
Engler, Thomas A.,Malhotra, Sushant,Burkholder, Timothy P.,Henry, James R.,Mendel, David,Porter, Warren J.,Furness, Kelly,Diefenbacher, Clive,Marquart, Angela,Reel, Jon K.,Li, Yihong,Clayton, Joshua,Cunningham, Brian,McLean, Johnathan,O'Toole, John C.,Brozinick, Joseph,Hawkins, Eric,Misener, Elizabeth,Briere, Daniel,Brier, Richard A.,Wagner, Jill R.,Campbell, Robert M.,Anderson, Bryan D.,Vaughn, Renee,Bennett, Donald B.,Meier, Timothy I.,Cook, James A.
, p. 899 - 903 (2007/10/03)
Many 3-aryl-4-(1,2,3,4-tetrahydro[1,4]diazepino[6,7,1-hi]indol-7-yl) maleimides exhibit potent GSK3 inhibitory activity (50), although few show significant selectivity (>100 ×) versus CDK2, CDK4, or PKCβII. However, combining 3-(imidazo[1,2-a]pyridin-3-yl), 3-(pyrazolo[1,5-a]pyridin-3-yl) or aza-analogs with a 4-(2-acyl-(1,2,3,4- tetrahydro[1,4]diazepino[6,7,1-hi]indol -7-yl)) group on the maleimide resulted in very potent inhibitors of GSK3 (≤5 nM) with >160 to >10,000-fold selectivity versus CDK2/4 and PKCβII. These compounds also inhibited tau phosphorylation in cells and were effective in lowering plasma glucose in a rat model of type 2 diabetes (ZDF rat).
