Development of new N-Arylbenzamides as STAT3 Dimerization Inhibitors.

ABSTRACT: The O-tosylsalicylamide S3I-201 (10) was used as a starting point for design and synthesis of novel STAT-3 dimerization inhibitors with improved drug-like qualities. The phosphonic acid 12d and salicylic acids 13f, 13g with a shorter amide linker lacking the O-tosyl group had improved STAT-3 inhibitory activity. The equivalent potencies observed by the replacement of phosphonic acid moiety of 12d with 5-amino-2-hydroxybenzoic acid group as in 13f further validates 5-amino-2-hydroxybenzoic acid as a phosphotyrosine mimic. The salicylic acid 13f displayed improved whole cell activity. The focused library of salicylic acids 13 with benzamide linker indicated that hydrophobic heptyl and cyclohexyl are the best tolerat

SUBMITTER: Urlam MK 

PROVIDER: S-EPMC3780559 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature