Design, Synthesis and Biological Evaluation of 1-methyl-1H-pyrazole-5-Carboxamide Derivatives as Novel Anti-Prostate Cancer Agents
Background: The androgen receptor (AR) signaling functions is a critical driving force for the progression of prostate cancer (PCa) to bring about anti-prostate cancer agents, and AR has been proved to be an effective therapeutic target even for castration-resistant prostate cancer (CRPC). Objective: In order to discover novel anti prostate cancer agents, we performed structural modifications based on the lead compounds T3 and 10e.Methods: A set of 1-methyl- 1H-pyrazole-5-carboxamide derivatives were synthesized and evaluated for their inhibitory activities against both expressions of prostate-specific antigen(PSA) and growth of PCa cell lines. Results: Compound H24 was found to be able to completely block PSA expression at 10 µM, and showed prominent antiproliferative activity in both the LNCaP cell line (GI 50 = 7.73 µM) and PC-3 cell line (GI 50 = 7.07 µM). Conclusions: These preliminary data supported a further evaluation of compound H24 as a potential agent to treat prostate cancer.