201286-68-2Relevant articles and documents
Substituted azabicyclic compounds
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, (2008/06/13)
This invention is directed to certain physiologically active compounds of formula (I) wherein represents a bicyclic ring system, of about 10 to about 13 ring members, in which the ring is an azaheterocycle, and the ring represents an azaheteroaryl ring, or an optionally halo substituted benzene ring; and N-oxides thereof, and their prodrugs, and pharmaceutically acceptable salts and solvates of the compounds of formula (I) and N-oxides thereof, and their prodrugs. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.
Orally active indole N-oxide PDE4 inhibitors
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.
, p. 3053 - 3058 (2007/10/03)
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.
