Development of Androgen-Antagonistic Coumarinamides with a Unique Aromatic Folded Pharmacophore.

ABSTRACT: First-generation nonsteroidal androgen receptor (AR) antagonists, such as flutamide (2a) and bicalutamide (3), are effective for most prostate cancer patients, but resistance often appears after several years due to the mutation of AR. Second-generation AR antagonists are effective against some of these castration-resistant prostate cancers, but their structural variety is still limited. In this study, we designed and synthesized 4-methyl-7-(N-alkyl-arylcarboxamido)coumarins as AR antagonist candidates and evaluated their growth-inhibitory activity toward androgen-dependent SC-3 cells. Coumarinamides with a secondary amide bond did not show inhibitory activity, but their N-methylated derivatives exhibited AR-antagonistic activity. Especially, 19b and 3

SUBMITTER: Koga H 

PROVIDER: S-EPMC7432827 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature