Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), UMR CNRS 7312, UFR Sciences, Moulin de La Housse and UFR Pharmacie, 51 Rue Cognacq-Jay, 51096 Reims, France.
Université de Reims-Champagne-Ardenne, EA 4691 Biomatériaux & Inflammation en Site OSseux (BIOS), SFR CAP-Santé (FED 4231), UFR Pharmacie and UFR Odontologie, 51 Rue Cognacq-Jay, 51096 Reims, France.
Eur J Med Chem. 2018 Feb 25;146:139-146. doi: 10.1016/j.ejmech.2018.01.035. Epub 2018 Jan 17.
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.
环核苷酸磷酸二酯酶 4（PDE4）可控制细胞内环核苷酸 cAMP 的水平，它作为呼吸疾病抗炎治疗的合适靶点引起了科学界的关注。在这里，我们描述了两类哒嗪酮衍生物作为潜在 PDE4 抑制剂的开发过程，并对它们作为抗炎剂的作用进行了评估。在这些衍生物中，4,5-二氢哒嗪酮代表物具有有前景的活性、对 PDE4 同工酶的选择性，并且能够减少人原代多形核细胞中 IL-8 的产生。
