3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts.

Autor: Brnardic EJ; Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. edward_brnardic@merck.com, Fraley ME, Garbaccio RM, Layton ME, Sanders JM, Culberson C, Jacobson MA, Magliaro BC, Hutson PH, O'Brien JA, Huszar SL, Uslaner JM, Fillgrove KL, Tang C, Kuo Y, Sur SM, Hartman GD
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 May 15; Vol. 20 (10), pp. 3129-33. Date of Electronic Publication: 2010 Mar 31.
DOI: 10.1016/j.bmcl.2010.03.089
Abstrakt: Hit to lead optimization of (5R)-5-hexyl-3-phenyl-1,3-oxazolidin-2-one as a positive allosteric modulator of mGluR2 is described. Improvements in potency and metabolic stability were achieved through SAR on both ends of the oxazolidinone. An optimized lead compound was found to be brain penetrant and active in a rat ketamine-induced hyperlocomotion model for antipsychotic activity.
(Copyright 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: