Shen Guangyuan, Yang Zimo, Lv Yue, Liu Huisi, Tian Xiaopian, Jia Xiangyu, Xia Yuanfeng, Wang Siqin, Jin Lei, Hu Zhilong, Yang Fanglong
Changchun Genescience Pharmaceuticals Co., Ltd., Shanghai 201203, PR China.
ACS Med Chem Lett. 2025 May 21;16(6):1175-1181. doi: 10.1021/acsmedchemlett.5c00222. eCollection 2025 Jun 12.
Recent clinical studies have heralded aldosterone synthase inhibitors (ASIs) as a promising therapeutic option for managing resistant hypertension. The efficacy of these compounds is believed to stem from their ability to mitigate aldosterone production. Consequently, we delved into the potential of aldosterone synthase inhibition as a therapeutic strategy for patients with refractory hypertension. Our focus is on the synthesis and optimization of innovative heterocyclic compounds that exhibit aldosterone synthase inhibitory activity. The CYP11B2 inhibitor we have developed exhibits an encouraging pharmacokinetic (PK) profile, along with a robust pharmacokinetic-pharmacodynamic (PK-PD) relationship. This has enabled us to meticulously evaluate the trends in aldosterone inhibition and assess the compound's efficacy in vivo using nonhuman primate models.
近期的临床研究已将醛固酮合酶抑制剂（ASIs）誉为治疗顽固性高血压的一种有前景的治疗选择。据信这些化合物的疗效源于其减轻醛固酮生成的能力。因此，我们深入研究了抑制醛固酮合酶作为难治性高血压患者治疗策略的潜力。我们专注于合成和优化具有醛固酮合酶抑制活性的新型杂环化合物。我们开发的CYP11B2抑制剂展现出令人鼓舞的药代动力学（PK）特征，以及强大的药代动力学-药效学（PK-PD）关系。这使我们能够细致地评估醛固酮抑制的趋势，并使用非人灵长类动物模型评估该化合物在体内的疗效。
