title: Rhodanine derivatives as novel inhibitors of PDE4.
abstract: The discovery, synthesis and in vitro activity of a novel series of rhodanine based phosphodiesterase-4 (PDE4) inhibitors is described. Structure-activity relationship studies directed toward improving potency led to the development of submicromolar inhibitors 2n and 3i (IC(50)=0.89 & 0.74 microM). The replacement of rhodanine with structurally related heterocycles was also investigated and led to the synthesis of pseudothiohydantoin 7 (IC(50)=0.31 microM).
authors.affiliation: Department of Chemistry, University of Paisley, High Street, Paisley, Renfrewshire PA1 2BE, UK. mark.irvine@ntlworld.com
authors.forename: Mark W
authors.initials: MW
authors.lastname: Irvine
authors.forename: Graham L
authors.initials: GL
authors.lastname: Patrick
authors.forename: Justin
authors.initials: J
authors.lastname: Kewney
authors.forename: Stuart F
authors.initials: SF
authors.lastname: Hastings
authors.forename: Simon J
authors.initials: SJ
authors.lastname: MacKenzie
mesh_terms: D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013867:Thiohydantoins / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D013867:Thiohydantoins; C529334:pseudothiohydantoin 7; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4