Synthesis and bioactivity of pyrazole and triazole derivatives as potential PDE4 inhibitors

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• 作者：Ya-Sheng Li^a ; ^&dagger ; ; Hao Tian^a ; ^&dagger ; ; Dong-Sheng Zhao^b ; ^&dagger ; ; De-Kun Hu^a ; Xing-Yu Liu^a ; Hong-Wei Jin^c ; Gao-Peng Song^d ; ^{vinsin1021@126.com" class="auth_mail" title="E-mail the corresponding author} ; Zi-Ning Cui^a ; ^{ziningcui@scau.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Synthesis ; 5-Phenyl-2-furan ; Pyrazole and triazole derivatives ; PDE4 inhibitor ; Molecular simulation
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 August 2016
• 年：2016
• 卷：26
• 期：15
• 页码：3632-3635
• 全文大小：1076 K

文摘

A series of pyrazole and triazole derivatives containing 5-phenyl-2-furan functionality were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. The bioassay results showed that title compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNFα release. Meanwhile, the activity of compounds containing 1,2,4-triazole (series II) was higher than that of pyrazole-attached derivatives (series I). The primary structure–activity relationship study and docking results showed that the 1,2,4-triazole moiety of compound IIk played a key role to form integral hydrogen bonds and π–π stacking interaction with PDE4B protein while the rest part of the molecule extended into the catalytic domain to block the access of cAMP and formed the foundation for inhibition of PDE4. Compound IIk would be great promise as a hit compound for further study based on the preliminary structure–activity relationship and molecular modeling studies.