A series of 3,5-dimethylpyrazole derivatives containing 5-phenyl-2-furan moiety were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. Bioassay results showed that the title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Among the designed compounds, compound If showed the best inhibitory activity against PDE4B with the IC₅₀ value of 1.7 μM, which also showed good in vivo activity in animal models of asthma/COPD and sepsis induced by LPS. The primary structure–activity relationship (SAR) study and docking results suggested that introduction of the substituent groups to the phenyl ring at the para-position, especially methoxy group, was helpful to enhance inhibitory activity against PDE4B.

设计并合成了一系列含有5-苯基-2-呋喃部分的3,5-二甲基吡唑衍生物，作为4型磷酸二酯酶（PDE4）抑制剂。生物测定结果表明，该标题化合物显示出相当大的抑制活性对PDE4B和LPS诱导的TNF阻断α释放。在设计的化合物中，化合物If对PDE4B表现出最佳的抑制活性，IC ₅₀值为1.7μM，在哮喘/ COPD和LPS诱发的败血症动物模型中也显示出良好的体内活性。初步的结构-活性关系（SAR）研究和对接结果表明，在对位苯环上引入取代基位置，特别是甲氧基，有助于增强对PDE4B的抑制活性。