Synthesis and anti-tumor activity of imidazopyrazines as TAK1 inhibitors.

Autor: Kang SJ; College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea; Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea., Lee JW; College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea., Chung SH; College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea., Jang SY; College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea; Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea., Choi J; Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea., Suh KH; Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea., Kim YH; Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea., Ham YJ; Department of Drug Discovery, Hanmi Research Center, Gyeonggi-do, 18469, Republic of Korea., Min KH; College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea. Electronic address: khmin@cau.ac.kr.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2019 Feb 01; Vol. 163, pp. 660-670. Date of Electronic Publication: 2018 Dec 13.
DOI: 10.1016/j.ejmech.2018.12.025
Abstrakt: Transforming growth factor-β activated kinase-1 (TAK1) is a potential therapeutic target for cancers and inflammatory diseases. We synthesized a series of novel imidazopyrazine derivatives, which were found to exhibit potent inhibitory effect against TAK1. Compound 22a, which possesses a good pharmacokinetic profile, showed excellent in vitro kinase activity and significant in vivo efficacy in mice xenografted with SW620, a KRAS-dependent colon cancer cell line.
(Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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