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Synthesis and biological evaluation of novel phthalazinone derivatives as topically active phosphodiesterase 4 inhibitors.

Abstract：

:Inhibitors of phosphodiesterase 4 (PDE4) are an important class of anti-inflammatory drug that act by inhibiting the production of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). We have synthesized and evaluated a series of 2-substituted phthalazinone derivatives as PDE4 inhibitors. Structure-activity relationship studies led to the identification of benzylamine-substituted phthalazinones as potent PDE4 inhibitors that also suppressed TNF-alpha production by whole rat blood cells. The most potent of these, when topically administered, were effective in a mouse model of dermatitis.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Kagayama K,Morimoto T,Nagata S,Katoh F,Zhang X,Inoue N,Hashino A,Kageyama K,Shikaura J,Niwa T

doi

10.1016/j.bmc.2009.08.014

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

6959-70

issue

19

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(09)00763-9

journal_volume

17

pub_type

杂志文章

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