Journal of Medicinal Chemistry p. 804 - 815 (2020)
Update date:2022-08-04
Topics:
Zhang, Shu-Wei
Gong, Chao-Jun
Su, Ming-Bo
Chen, Fei
He, Ting
Zhang, Yang-Ming
Shen, Qian-Qian
Su, Yi
Ding, Jian
Li, Jia
Chen, Yi
Nan, Fa-Jun
A series of bisthiazole-based hydroxamic acids as novel potent HDAC inhibitors was developed during our previous work. In the present work, a new series of highly potent bisthiazole-based compounds were designed and synthesized. Among the prepared compounds, compound H13, which contains an α-(S)-methyl-substituted benzyl group, displays potent inhibitory activity toward human HDACs and several cancer cells lines. Compound H13 has a favorable PK profile and high tissue distribution specificity in the colon, as well as good efficacy in the AOM-DSS mouse model for colitis-associated colonic tumorigenesis.
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