Orally active indole N-oxide PDE4 inhibitors.

Abstract 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 IC 50 '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.