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2,4-二取代-5-(6-烷基吡啶-2-基)-1-咪唑类化合物的合成、生物评价及分子模拟作为 ALK5 抑制剂。

Synthesis, biological evaluation and molecular modelling of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1-imidazoles as ALK5 inhibitors.

机构信息

Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, South Korea.

School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.

出版信息

J Enzyme Inhib Med Chem. 2020 Dec;35(1):702-712. doi: 10.1080/14756366.2020.1734799.

DOI:10.1080/14756366.2020.1734799
PMID:32164459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7144182/
Abstract

A series of 2,4-disubstituted-5-(6-alkylpyridin-2-yl)-1-imidazoles, , , and 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 CONH substituent in the phenyl ring generated a highly potent and selective ALK5 inhibitor . Docking model of ALK5 in complex with showed that it fitted well in the ATP-binding pocket with favourable interactions.

摘要

已经合成了一系列 2,4-二取代-5-(6-烷基吡啶-2-基)-1-咪唑并[1,2-a]嘧啶，并在酶测定和基于细胞的荧光素酶报告基因测定中评估了它们对 ALK5 的抑制活性。在咪唑环的 4-和 2-位分别引入喹喔啉-6-基部分和亚甲基连接基，以及苯环上的 CONH 取代基，生成了一种高效且选择性的 ALK5 抑制剂 。ALK5 与 的复合物的对接模型表明，它与 ATP 结合口袋结合良好，具有有利的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/062a0c2cb4d9/IENZ_A_1734799_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/d9fc4e1ec665/IENZ_A_1734799_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/900c61fd7c64/IENZ_A_1734799_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/6ccf2b6cd869/IENZ_A_1734799_SCH0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/00f3d5d8e701/IENZ_A_1734799_SCH0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/6d3a7ad3c3be/IENZ_A_1734799_SCH0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/f0feddad85d0/IENZ_A_1734799_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/062a0c2cb4d9/IENZ_A_1734799_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/d9fc4e1ec665/IENZ_A_1734799_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/900c61fd7c64/IENZ_A_1734799_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/6ccf2b6cd869/IENZ_A_1734799_SCH0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/00f3d5d8e701/IENZ_A_1734799_SCH0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/6d3a7ad3c3be/IENZ_A_1734799_SCH0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/f0feddad85d0/IENZ_A_1734799_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7550/7144182/062a0c2cb4d9/IENZ_A_1734799_F0003_C.jpg

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Transforming Growth Factor-β Signaling in Immunity and Cancer.转化生长因子-β 信号在免疫和癌症中的作用。
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