2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2008 Oct 1;18(19):5303-6. doi: 10.1016/j.bmcl.2008.08.040.
Donald S Middleton 1,  Mark Andrews,  Paul Glossop,  Geoffrey Gymer,  David Hepworth,  Alan Jessiman,  Patrick S Johnson,  Malcolm MacKenny,  Alan Stobie,  Kim Tang,  Paul Morgan,  Barry Jones
Affiliations

Affiliation

  • 1 Department of Discovery Chemistry (B500, IPC 324), Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. [email protected]
PMID: 18782666 DOI: 10.1016/j.bmcl.2008.08.040
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.

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