Synthesis and characterization of 8-ethynyl-1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: new potent non-competitive metabotropic glutamate receptor 2/3 antagonists. Part 1.
A series of 1,3-dihydrobenzo[b][1,4]diazepin-2-one derivatives was evaluated as non-competitive mGluR2/3 antagonists. Attachment of an 8-(2-aryl)-ethynyl-moiety 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.
Woltering
Thomas J
TJ
F. Hoffmann-La Roche Ltd, Pharma Discovery Chemistry, CNS CH-4070 Basel, Switzerland.
Adam
Geo
G
Alanine
Alexander
A
Wichmann
Jürgen
J
Knoflach
Frédéric
F
Mutel
Vincent
V
Gatti
Silvia
S
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015394:Molecular Structure; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism*
C525800:8-ethynyl-1,3-dihydro-benzo(b)(1,4)diazepin-2-one; D001381:Azepines; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3