title: CDP840. A prototype of a novel class of orally active anti-inflammatory phosphodiesterase 4 inhibitors.
abstract: The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 (29), a potent, chiral, selective inhibitor of PDE 4 (IC(50) 4nM). CDP840 is non-emetic in the ferret at 30mgkg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig.
authors.affiliation: Department of Medicinal Chemistry, Celltech R&D Ltd., 208 Bath Road, Slough, Berkshire SL1 3WE, UK. rikki.alexander@celltechgroup.com
authors.forename: R P
authors.initials: RP
authors.lastname: Alexander
authors.forename: G J
authors.initials: GJ
authors.lastname: Warrellow
authors.forename: M A W
authors.initials: MA
authors.lastname: Eaton
authors.forename: E C
authors.initials: EC
authors.lastname: Boyd
authors.forename: J C
authors.initials: JC
authors.lastname: Head
authors.forename: J R
authors.initials: JR
authors.lastname: Porter
authors.forename: J A
authors.initials: JA
authors.lastname: Brown
authors.forename: J T
authors.initials: JT
authors.lastname: Reuberson
authors.forename: B
authors.initials: B
authors.lastname: Hutchinson
authors.forename: P
authors.initials: P
authors.lastname: Turner
authors.forename: B
authors.initials: B
authors.lastname: Boyce
authors.forename: D
authors.initials: D
authors.lastname: Barnes
authors.forename: B
authors.initials: B
authors.lastname: Mason
authors.forename: A
authors.initials: A
authors.lastname: Cannell
authors.forename: R J
authors.initials: RJ
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Zomaya
authors.forename: A
authors.initials: A
authors.lastname: Millican
authors.forename: J
authors.initials: J
authors.lastname: Leonard
authors.forename: R
authors.initials: R
authors.lastname: Morphy
authors.forename: M
authors.initials: M
authors.lastname: Wales
authors.forename: M
authors.initials: M
authors.lastname: Perry
authors.forename: R A
authors.initials: RA
authors.lastname: Allen
authors.forename: N
authors.initials: N
authors.lastname: Gozzard
authors.forename: B
authors.initials: B
authors.lastname: Hughes
authors.forename: G
authors.initials: G
authors.lastname: Higgs
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy; D016084:Bronchoconstriction / Q000187:drug effects; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D006168:Guinea Pigs; D006801:Humans; D020128:Inhibitory Concentration 50; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D011725:Pyridines / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D020889:Rolipram / Q000031:analogs & derivatives; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C102660:CDP 840; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram