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The Structure‐Activity Relationship Study of Dicarboximide‐phenylpyridine Conjugates as Inhibitors of Wnt Signaling Pathway
Author(s) -
Wu Hongna,
Wu Jun,
Qin Tong,
Lian Xu,
Li Zhongwen,
Guo Baojie,
Hao Jie,
Li Tianlei,
Zhang Wenxuan,
Wu Song
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202003619
Subject(s) - wnt signaling pathway , chemistry , lead compound , stereochemistry , structure–activity relationship , inhibitory postsynaptic potential , conjugate , cyclohexene , ic50 , biochemistry , signal transduction , in vitro , biology , endocrinology , catalysis , mathematical analysis , mathematics
Inhibition of the aberrant Wnt pathway is a promising approach for the treatment of various types of disease. Based on the previous SAR results, we continued to optimize the structure of the dicarboximide‐phenylpyridine conjugates as the Wnt pathway inhibitors. Two cis ‐4‐cyclohexene‐1, 2‐dicarboximide derivatives 6 and 16 showed much better wnt inhibitory activity than that of the lead compound among the eighteen novel compounds. The IC 50 of the most potent compound 16 was 30 nM, which was about 10‐folds more potent than the lead compound 1 b , and 100‐folds more potent than the hit compound 1 a . Although the compounds have similar structure with tankyrases inhibitor IWR‐1 series compounds, they did not inhibit tankyrase 1/2, indicating they had different mechanism.
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