2. Academic Validation
  3. Synthesis and bioactivity of pyrazole and triazole derivatives as potential PDE4 inhibitors

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

  • Bioorg Med Chem Lett. 2016 Aug 1;26(15):3632-5. doi: 10.1016/j.bmcl.2016.06.002.
Ya-Sheng Li 1,  Hao Tian 1,  Dong-Sheng Zhao 2,  De-Kun Hu 1,  Xing-Yu Liu 1,  Hong-Wei Jin 3,  Gao-Peng Song 4,  Zi-Ning Cui 5
Affiliations

Affiliations

  • 1 State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Integrative Microbiology Research Centre, Guangdong Province Key Laboratory of Microbial Signals and Disease Control, South China Agricultural University, Guangzhou 510642, China.
  • 2 Department of Pharmacy, Quanzhou Medical College, Quanzhou 362100, China.
  • 3 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 4 College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China. Electronic address: vinsin1021@126.com.
  • 5 State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Integrative Microbiology Research Centre, Guangdong Province Key Laboratory of Microbial Signals and Disease Control, South China Agricultural University, Guangzhou 510642, China. Electronic address: ziningcui@scau.edu.cn.
PMID: 27289320 DOI: 10.1016/j.bmcl.2016.06.002
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 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.

Keywords

5-Phenyl-2-furan; Molecular simulation; PDE4 inhibitor; Pyrazole and triazole derivatives; Synthesis.

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