684222-75-1Relevant academic research and scientific papers
Discovery of piperazinylimidazo[1,2-a]pyridines as novel S4 binding elements for orally active Factor Xa inhibitors
Imaeda, Yasuhiro,Kawamoto, Tetsuji,Tobisu, Mamoru,Konishi, Noriko,Hiroe, Katsuhiko,Kawamura, Masaki,Tanaka, Toshimasa,Kubo, Keiji
, p. 3125 - 3140 (2008)
We have recently reported the discovery of orally active sulfonylalkylamide Factor Xa (FXa) inhibitors, as typified by compound 1 (FXa IC50 = 0.061 μM). Since the pyridylpiperidine moiety was not investigated in our previous study, we conducted detailed structure-activity relationship studies on this S4 binding element. This investigation led to the discovery of piperazinylimidazo[1,2-a]pyridine 2b as a novel and potent FXa inhibitor (FXa IC50 = 0.021 μM). Further modification resulted in the discovery of 2-hydroxymethylimidazo[1,2-a]pyridine 2e (FXa IC50 = 0.0090 μM), which was found to be a selective and orally bioavailable FXa inhibitor with reduced CYP3A4 inhibition.
