NADPH oxidases (Nox enzymes) are critical mediators of both physiologic and pathophysiologic processes. Nox enzymes catalyze NADPH-dependent generation of reactive oxygen species (ROS), including superoxide and hydrogen peroxide. Until recently, Nox4 was proposed to be involved exclusively in normal physiologic functions. Compelling evidence, however, suggests that Nox4 plays a critical role in fibrosis, as well as a host of pathologies and diseases. These considerations led to a search for novel, small molecule inhibitors of this important enzyme. Ultimately, a series of novel tertiary sulfonylureas (23–25) was designed using pharmacophore modeling, synthesized, and evaluated for inhibition of Nox4-dependent signaling.

NADPH 氧化酶（Nox 酶）是生理和病理生理过程的关键介质。Nox 酶催化 NADPH 依赖性活性氧 (ROS) 的生成，包括超氧化物和过氧化氢。直到最近，Nox4 才被认为只参与正常的生理功能。然而，令人信服的证据表明，Nox4 在纤维化以及许多病理和疾病中发挥着关键作用。这些考虑导致人们寻找这种重要酶的新型小分子抑制剂。最终，使用药效团模型设计、合成了一系列新型三级磺酰脲类药物 ( 23 – 25 )，并评估其对 Nox4 依赖性信号传导的抑制作用。