Synthesis and in Vitro and in Vivo Biological Evaluation of Tissue-Specific Bisthiazole Histone Deacetylase (HDAC) Inhibitors.

Basic Information

ID: ALA4354838

Journal: J Med Chem

Title: Synthesis and in Vitro and in Vivo Biological Evaluation of Tissue-Specific Bisthiazole Histone Deacetylase (HDAC) Inhibitors.

Authors: Zhang SW, Gong CJ, Su MB, Chen F, He T, Zhang YM, Shen QQ, Su Y, Ding J, Li J, Chen Y, Nan FJ.

Abstract: 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.

CiteXplore: 31855601

DOI: 10.1021/acs.jmedchem.9b01792

Patent ID: