Background: The Androgen Receptor (AR) signaling functionis 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 10μM, and showed prominent antiproliferative activity in both the LNCaP cell line (GI₅₀ = 7.73μM) and PC-3 cell line (GI₅₀ = 7.07μM).

Conclusion: These preliminary data supported a further evaluation of compound H24 as a potential agent to treat prostate cancer.

背景：雄激素受体 (AR) 信号功能是前列腺癌 (PCa) 进展的关键驱动力，从而产生抗前列腺癌药物，AR 已被证明是一种有效的治疗靶点，即使是去势抵抗性前列腺癌(CRPC)。目的：为了发现新型抗前列腺癌药物，我们在先导化合物 T3 和 10e 的基础上进行了结构修饰。

方法：合成了一组 1-甲基-1H-吡唑-5-甲酰胺衍生物，并评估了它们对前列腺特异性抗原 (PSA) 表达和 PCa 细胞系生长的抑制活性。

结果：发现化合物H24能够在10μM时完全阻断PSA表达，并且在LNCaP细胞系（GI ₅₀ = 7.73μM）和PC-3细胞系（GI ₅₀ = 7.07μM）中均显示出显着的抗增殖活性。

结论：这些初步数据支持进一步评估化合物 H24 作为治疗前列腺癌的潜在药物。