Cyclic nucleotide phosphodiesterase type 4 (PDE4), that controls intracellular level of cyclic nucleotide cAMP, has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases. Here we describe the development of two families of pyridazinone derivatives as potential PDE4 inhibitors and their evaluation as anti-inflammatory agents. Among these derivatives, 4,5-dihydropyridazinone representatives possess promising activity, selectivity towards PDE4 isoenzymes and are able to reduce IL-8 production by human primary polymorphonuclear cells.

中文翻译：

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哒嗪酮衍生物作为潜在抗炎药的合成及生物学评价

控制环核苷酸cAMP的细胞内水平的4型环核苷酸磷酸二酯酶（PDE4）作为呼吸道疾病抗炎治疗的合适靶点已引起科学界的关注。在这里，我们描述了作为潜在PDE4抑制剂的哒嗪酮衍生物的两个家族的发展及其作为抗炎药的评估。在这些衍生物中，4,5-二氢哒嗪酮代表具有有前途的活性，对PDE4同工酶的选择性，并能够减少人原代多形核细胞产生IL-8。