title: The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I.
abstract: This communication describes the synthesis and in vitro evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. The compounds described contain an indole moiety which replaces the 'rolipram-like' 3-methoxy-4-cyclopentoxy motif. Several of the compounds presented possess low nanomolar IC50's for PDEIV inhibition. In vivo activities determined from measurement of serum TNF-alpha levels in LPS challenged mice (mouse endotoxemia model) are also reported.
authors.affiliation: Rhône-Poulenc Rorer Central Research, Collegeville, PA 19426, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hulme
authors.forename: K
authors.initials: K
authors.lastname: Moriarty
authors.forename: B
authors.initials: B
authors.lastname: Miller
authors.forename: R
authors.initials: R
authors.lastname: Mathew
authors.forename: M
authors.initials: M
authors.lastname: Ramanjulu
authors.forename: P
authors.initials: P
authors.lastname: Cox
authors.forename: J
authors.initials: J
authors.lastname: Souness
authors.forename: K M
authors.initials: KM
authors.lastname: Page
authors.forename: J
authors.initials: J
authors.lastname: Uhl
authors.forename: J
authors.initials: J
authors.lastname: Travis
authors.forename: F C
authors.initials: FC
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Labaudiniere
authors.forename: S W
authors.initials: SW
authors.lastname: Djuric
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001682:Biological Availability; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004341:Drug Evaluation; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram