title: Synthesis and characterization of 8-ethynyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: part 2. New potent non-competitive metabotropic glutamate receptor 2/3 antagonists.
abstract: A series of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives was evaluated as non-competitive mGluR2/3 antagonists. Replacement of a cyano group by a five-membered heterocycle produced compounds inhibiting the binding of [(3)H]-LY354740 to rat mGluR2 with low nanomolar affinity and consistent functional effect at both mGluR2 and mGluR3. Further modification to improve the physicochemical properties led eventually to compounds with the ability to reverse LY354740-mediated inhibition of field excitatory postsynaptic potentials in the rat dentate gyrus.
authors: F. Hoffmann-La Roche Ltd, Pharma Discovery Chemistry, CH-4070 Basel, Switzerland. thomas.woltering@roche.com
authors: Thomas J
authors: TJ
authors: Woltering
authors: Geo
authors: G
authors: Adam
authors: Jürgen
authors: J
authors: Wichmann
authors: Erwin
authors: E
authors: Goetschi
authors: James N C
authors: JN
authors: Kew
authors: Frédéric
authors: F
authors: Knoflach
authors: Vincent
authors: V
authors: Mutel
authors: Silvia
authors: S
authors: Gatti
mesh_terms: D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015394:Molecular Structure; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C525800:8-ethynyl-1,3-dihydro-benzo(b)(1,4)diazepin-2-one; D001381:Azepines; D001643:Bridged Bicyclo Compounds; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104753:eglumetad