Synthesis and characterization of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: Part 3. New potent non-competitive metabotropic glutamate receptor 2/3 antagonists
- 作者：Thomas J. Woltering ; Jü ; rgen Wichmann ; Erwin Goetschi ; Geo Adam ; James N.C. Kew ; Fré ; dé ; ric Knoflach ; Theresa M. Ballard ; Jö ; rg Huwyler ; Vincent Mutel ; Silvia Gatti
- 关键词：Metabotropic glutamate receptors ; 1 ; 3-Dihydro-benzo[b][1 ; 4]diazepin-2-one ; mGluR2 antagonist ; LY354740 ; In vivo activity ; Mice
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：15 April 2008
- 卷：18
- 期：8
- 页码：2725-2729
- 文件大小：166 K
摘要
A series of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives was evaluated as non-competitive mGluR2/3 antagonists. Replacement of the (2-aryl)-ethynyl-moiety in 8-position with smaller less lipophilic substituents produced compounds inhibiting the binding of [3H]-LY354740 to rat mGluR2 with low nanomolar affinity and consistent functional effect at both mGluR2 and mGluR3. These compounds were able to reverse LY354740-mediated inhibition of field excitatory postsynaptic potentials in the rat dentate gyrus and in vivo activity could be demonstrated by reversal of the LY354740-induced hypoactivity in mice after oral administration.