Synthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles as inhibitors of transforming growth factor-β type i receptor kinase
- 주제(키워드) ALK5 inhibitor , Cancer , Fibrosis , Kinase assay , TGF-β
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Ltd
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000120183
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.bmcl.2015.09.058
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
To further optimize a clinical candidate 5 (EW-7197), a series of 5-(3-, 4-, or 5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19a-l have been synthesized and evaluated for their TGF-β type I receptor kinase (ALK5) and p38α MAP kinase inhibitory activity in an enzyme assay. The 5-(5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19h-l displayed the similar level of potency to that of 5 against both ALK5 (IC50 = 7.68-13.70 nM) and p38α MAP kinase (IC50 = 1240-3370 nM). Among them, 19j inhibited ALK5 with IC50 value of 7.68 nM in a kinase assay and displayed 82% inhibition at 100 nM in a luciferase reporter assay. © 2015 Elsevier Ltd. All rights reserved.
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