کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1364105 | 981529 | 2007 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110α inhibitors Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110α inhibitors](/preview/png/1364105.png)
We have previously reported the imidazo[1,2-a]pyridine derivative 4 as a novel p110α inhibitor; however, although 4 is a potent inhibitor of p110α enzymatic activity and tumor cell proliferation in vitro, it is unstable in solution and ineffective in vivo. To increase stability the pyrazole of 4 was replaced with a hydrazone and a moderately potent p110α inhibitor 7a was obtained. Subsequent optimization of 7a afforded exceptionally potent p110α inhibitors, including 8c and 8h, with IC50 values of 0.30 nM and 0.26 nM, respectively; to the best of our knowledge, these compounds are the most potent PI3K p110α inhibitors reported to date. Compound 8c was also stable in solution and exhibited significant anti-tumor effectiveness in vivo.
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Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 17, 1 September 2007, Pages 5837–5844