کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1356851 | 981163 | 2008 | 17 صفحه PDF | دانلود رایگان |
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.
Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 3, 1 February 2008, Pages 1359–1375