Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles as ALK5 inhibitors
- 주제(키워드) 2 , 4-Disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles , ALK5 inhibition , cancer immunotherapeutic agent , docking
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Chemistry, Medicinal
- 설명문(일반) [Park, Myoung-Soon; An, Young Jae; Choi, Joon Hun; Cha, Geunyoung; Lee, Hwa Jeong; Dewang, Purushottam M.; Kim, Dae-Kee] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, 52 Ewhayeodae Gil, Seoul 03760, South Korea; [Park, Hyun-Ju; Park, So-Jung] Sungkyunkwan Univ, Sch Pharm, Suwon, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 TAYLOR & FRANCIS LTD
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168888
- 본문언어 영어
- Published As https://dx.doi.org/10.1080/14756366.2020.1734799
- PubMed https://pubmed.ncbi.nlm.nih.gov/32164459
초록/요약
A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1H-imidazoles, 7a-c, 11a-h, and 16a-h has been synthesised and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Incorporation of a quinoxalin-6-yl moiety and a methylene linker at the 4- and 2-position of the imidazole ring, respectively, and a m-CONH2 substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor 11e. Docking model of ALK5 in complex with 11e showed that it fitted well in the ATP-binding pocket with favourable interactions.
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