Discovery of N-sulfonylated aminosalicylic acids as dual MCL-1/BCL-xL inhibitors.

ABSTRACT: The anti-apoptotic protein MCL-1, which is overexpressed in multiple cancers, is presently a focus for the development of targeted drugs in oncology. We previously discovered inhibitors of MCL-1 based on 1-sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acids ("1,6-THQs"). However, with the nitrogen atom constrained in the bicyclic ring, we were unable to modify the alkyl portion of the tertiary sulfonamide functionality. Moreover, the introduction of additional functional groups onto the benzene ring portion of the THQ bicycle would not be trivial. Therefore, we elected to deconstruct the piperidine-type ring of the 6-carboxy-THQ lead to create a new 4-aminobenzoic acid scaffold. Given its simplicity, this permitted us to introduce diversity at the sulfonamide nitrogen, as well as v

SUBMITTER: Chen L 

PROVIDER: S-EPMC9890589 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature