title: Identification of pyridazino[4,5-b]indolizines as selective PDE4B inhibitors.
abstract: Substituted pyridazino[4,5-b]indolizines were identified as potent and selective PDE4B inhibitors. We describe the structure-activity relationships generated around an HTS hit that led to a series of compounds with low nanomolar affinity for PDE4B and high selectivity over the PDE4D subtype.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Global Research and Development, CN 8000, Princeton, NJ 08543, USA. donnela@wyeth.com
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Donnell
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dollings
authors.forename: John A
authors.initials: JA
authors.lastname: Butera
authors.forename: Arlene J
authors.initials: AJ
authors.lastname: Dietrich
authors.forename: Kerri K
authors.initials: KK
authors.lastname: Lipinski
authors.forename: Afshin
authors.initials: A
authors.lastname: Ghavami
authors.forename: Warren D
authors.initials: WD
authors.lastname: Hirst
mesh_terms: D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D006801:Humans; D007212:Indolizines / Q000737:chemistry* / Q000494:pharmacology*; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007212:Indolizines; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4