Rhodanine derivatives as novel inhibitors of PDE4.
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).
Irvine
Mark W
MW
Department of Chemistry, University of Paisley, High Street, Paisley, Renfrewshire PA1 2BE, UK. mark.irvine@ntlworld.com
Patrick
Graham L
GL
Kewney
Justin
J
Hastings
Stuart F
SF
MacKenzie
Simon J
SJ
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*
D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D013867:Thiohydantoins; C529334:pseudothiohydantoin 7; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4