Imidazo[1,2-a]pyrimidines as functionally selective and orally bioavailable GABA(A)alpha2/alpha3 binding site agonists for the treatment of anxiety disorders

  • J Med Chem. 2006 Jan 12;49(1):35-8. doi: 10.1021/jm051065l.
Simon C Goodacre  1 ,  Leslie J Street ,  David J Hallett ,  James M Crawforth ,  Sarah Kelly ,  Andrew P Owens ,  Wesley P Blackaby ,  Richard T Lewis ,  Joanna Stanley ,  Alison J Smith ,  Pushpinder Ferris ,  Bindi Sohal ,  Susan M Cook ,  Andrew Pike ,  Nicola Brown ,  Keith A Wafford ,  George Marshall ,  José L Castro ,  John R Atack
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Sharp Laboratory, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex, UK.
PMID: 16392789 DOI: 10.1021/jm051065l
Abstract

A series of high-affinity GABA(A) agonists with good oral bioavailability in rat and dog and functional selectivity for the GABA(A)alpha2 and -alpha3 subtypes is reported. The 7-trifluoromethylimidazopyrimidine 14g and the 7-propan-2-olimidazopyrimidine 14k are anxiolytic in both conditioned and unconditioned animal models of anxiety with minimal sedation observed at full BZ binding site occupancy.

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