title: Designing rapid onset selective serotonin re-uptake inhibitors. Part 3: Site-directed metabolism as a strategy to avoid active circulating metabolites: structure-activity relationships of (thioalkyl)phenoxy benzylamines.
abstract: A series of thio-alkyl containing diphenylethers were designed and evaluated, as a strategy to competitively direct metabolism away from unwanted amine N-demethylation and deliver a pharmacologically inactive S-oxide metabolite. Overall, sulfonamide 20 was found to possess the best balance of target pharmacology, pharmacokinetics and metabolism profile.
authors.affiliation: Department of Discovery Chemistry (B500, IPC 324), Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. don.s.middleton@pfizer.com
authors.forename: Donald S
authors.initials: DS
authors.lastname: Middleton
authors.forename: Mark
authors.initials: M
authors.lastname: Andrews
authors.forename: Paul
authors.initials: P
authors.lastname: Glossop
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Gymer
authors.forename: David
authors.initials: D
authors.lastname: Hepworth
authors.forename: Alan
authors.initials: A
authors.lastname: Jessiman
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Johnson
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacKenny
authors.forename: Alan
authors.initials: A
authors.lastname: Stobie
authors.forename: Kim
authors.initials: K
authors.lastname: Tang
authors.forename: Paul
authors.initials: P
authors.lastname: Morgan
authors.forename: Barry
authors.initials: B
authors.lastname: Jones
mesh_terms: D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001596:Benzylamines; D010647:Phenyl Ethers; D017367:Selective Serotonin Reuptake Inhibitors; D013449:Sulfonamides