Synthesis and bioactivity of pyrazole and triazole derivatives as potential PDE4 inhibitors. Issue 15 (1st August 2016)

• Record Type: Journal Article
• Authors: Li, Ya-Sheng; Tian, Hao; Zhao, Dong-Sheng; Hu, De-Kun; Liu, Xing-Yu; Jin, Hong-Wei; Song, Gao-Peng; Cui, Zi-Ning
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 15(2016)
• Page Start: 3632
• Page End: 3635
• Publication Date: 2016-08-01
• Subjects: Synthesis -- 5-Phenyl-2-furan -- Pyrazole and triazole derivatives -- PDE4 inhibitor -- Molecular simulation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.06.002
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 TNF α release. Meanwhile, the activity of compounds containing 1, 2, 4-triazole (seriesII ) was higher than that of pyrazole-attached derivatives (seriesI ). The primary structure–activity relationship study and docking results showed that the 1, 2, 4-triazole moiety of compoundIIk 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. CompoundIIk would be great promise as a hit compound for further study based on the preliminary structure–activity relationship and molecular modeling studies.