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  3. Synthesis and bioactivity of phenyl substituted furan and oxazole carboxylic acid derivatives as potential PDE4 inhibitors

Synthesis and bioactivity of phenyl substituted furan and oxazole carboxylic acid derivatives as potential PDE4 inhibitors

  • Eur J Med Chem. 2020 Dec 1;207:112795. doi: 10.1016/j.ejmech.2020.112795.
Yinuo Lin 1,  Wasim Ahmed 1,  Min He 1,  Xuwen Xiang 1,  Riyuan Tang 2,  Zi-Ning Cui 3
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 Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Department of Applied Chemistry, College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China. Electronic address: [email protected].
  • 3 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; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China. Electronic address: [email protected].
PMID: 33002845 DOI: 10.1016/j.ejmech.2020.112795
Abstract

In this present study, a series of 5-phenyl-2-furan and 4-phenyl-2-oxazole derivatives were designed and synthesized as phosphodiesterase type 4 (PDE4) inhibitors. In vitro results showed that the synthesized compounds exhibited considerable inhibitory activity against PDE4B and blockade of LPS-induced TNF-α release. Among the designed compounds, Compound 5j exhibited lower IC50 value (1.4 μM) against PDE4 than parent rolipram (2.0 μM) in in vitro Enzyme assay, which also displayed good in vivo activity in animal models of asthma/COPD and sepsis induced by LPS. Docking results suggested that introduction of methoxy group at para-position of phenyl ring, demonstrated good interaction with metal binding pocket domain of PDE4B, which was helpful to enhance inhibitory activity.

Keywords

2-cyanoimino-1,3-thiazolidine; 4-phenyl-2-oxazole; 5-phenyl-2-furan; Molecular simulation; PDE4 inhibitors; Synthesis.

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