Bioorganic and Medicinal Chemistry Letters p. 3053 - 3058 (1998)
Update date:2022-08-04
Topics:
Hulme, Christopher
Mathew, Rose
Moriarty, Kevin
Miller, Bruce
Ramanjulu, Mercy
Cox, Paul
Souness, John
Page, Ken M.
Uhl, Joanne
Travis, Jeffrey
Labaudiniere, Richard
Huang, Fu-Chih
Djuric, Stevan W.
This communication describes the synthesis and in vitro and in vivo evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. Several of the compounds presented possess low nanomolar IC50's for PDE4 inhibition and excellent in vivo activity for inhibition of TNF-α levels in LPS challenged mice (mouse endotoxemia model). Emesis studies (dog) and efficacy in a SCW arthritis model for the most potent PDE4 inhibitors are presented.
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