| Literature DB >> 17983756 |
Mark J Mulvihill1, Qun-Sheng Ji, Heather R Coate, Andrew Cooke, Hanqing Dong, Lixin Feng, Kenneth Foreman, Maryland Rosenfeld-Franklin, Ayako Honda, Gilda Mak, Kristen M Mulvihill, Anthony I Nigro, Matthew O'Connor, Caroline Pirrit, Arno G Steinig, Kam Siu, Kathryn M Stolz, Yingchuan Sun, Paula A R Tavares, Yan Yao, Neil W Gibson.
Abstract
A series of novel, potent quinolinyl-derived imidazo[1,5-a]pyrazine IGF-IR (IGF-1R) inhibitors--most notably, cis-3-(3-azetidin-1-ylmethylcyclobutyl)-1-(2-phenylquinolin-7-yl)imidazo[1,5-a]pyrazin-8-ylamine (AQIP)--is described. Synthetic details, structure-activity relationships, and in vitro biological activity are reported for the series. Key in vitro and in vivo biological results for AQIP are reported, including: inhibition of ligand-stimulated autophosphorylation of IGF-IR and downstream pathways in 3T3/huIGFIR cells; inhibition of proliferation and induction of DNA fragmentation in human tumor cell lines; a pharmacokinetic profile suitable for once-per-day oral dosing; antitumor activity in a 3T3/huIGFIR xenograft model; and effects on insulin and glucose levels.Entities:
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Year: 2007 PMID： 17983756 DOI： 10.1016/j.bmc.2007.10.061
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641