1. Discovery of an Orally Efficacious Imidazo[5,1-f][1,2,4]triazine Dual Inhibitor of IGF-1R and IR
- Author
-
Andrew Kleinberg, Prafulla C. Gokhale, Kathryn M. Stolz, Yan Yao, Andy Cooke, An-Hu Li, Douglas S. Werner, Robert A. Wild, Darla Landfair, Arno G. Steinig, Earl W. May, Mark Bittner, Elizabeth Buck, Hanqing Dong, Mark J. Mulvihill, Jonathan A. Pachter, Radoslaw Laufer, Mridula Kadalbajoo, Lixin Feng, Kam W. Siu, Kenneth Foreman, and Meizhong Jin
- Subjects
biology ,business.industry ,Organic Chemistry ,Dual inhibitor ,Biological activity ,Pharmacology ,Biochemistry ,chemistry.chemical_compound ,Insulin receptor ,chemistry ,In vivo ,Drug Discovery ,biology.protein ,Medicine ,business ,Receptor ,Tumor xenograft ,Triazine - Abstract
This report describes the investigation of a series of 5,7-disubstituted imidazo[5,1-f][1,2,4]triazine inhibitors of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR). Structure−activity relationship exploration and optimization leading to the identification, characterization, and pharmacological activity of compound 9b, a potent, selective, well-tolerated, and orally bioavailable dual inhibitor of IGF-1R and IR with in vivo efficacy in tumor xenograft models, is discussed.
- Published
- 2010