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Discovery of novel 5‐methyl‐1 H ‐pyrazole derivatives as potential antiprostate cancer agents: Design, synthesis, molecular modeling, and biological evaluation
Author(s) -
Zhang Daoguang,
Asnake Solomon,
Zhang Jingya,
Olsson PerErik,
Zhao Guisen
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13173
Subject(s) - pyrazole , androgen receptor , prostate cancer , enzalutamide , chemistry , reporter gene , cancer , cancer research , combinatorial chemistry , biochemistry , stereochemistry , gene , biology , medicine , gene expression
Androgen receptor ( AR ) signaling functions as a core driving force for the progression of prostate cancer ( PC a), and AR has been proved to be an effective therapeutic target even for castration‐resistant prostate cancer ( CRPC ). Herein, structural modification via a fragments splicing strategy was performed based on two lead compounds T3 and 10e , leading to the discovery of a series of 5‐methyl‐1 H ‐pyrazole derivatives. AR reporter gene assay revealed compounds A13 and A14 as potent AR antagonists. Some of the compounds in this series inhibited growth of PC a LNC aP cells more efficiently than enzalutamide. A13 and A14 also showed improved metabolic stability compared with 10e in human liver microsomes.