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Synthesis and bioactivity of 3,5-dimethylpyrazole derivatives as potential PDE4 inhibitors.

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Hu DK,Zhao DS,He M,Jin HW,Tang YM,Zhang LH,Song GP,Cui ZN

doi

10.1016/j.bmcl.2018.03.031

subject

Has Abstract

pub_date

2018-10-15 00:00:00

pages

3276-3280

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(18)30220-8

journal_volume

28

pub_type

杂志文章

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