Tiffany Hoerter - 2,6-Disubstituted pyrazines and related analogs as NR2B site antagonists of the NMDA receptor with anti-depressant activity.

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      Publication Details (including relevant citation   information):

    2,6-Disubstituted pyrazines and related analogs as NR2B site antagonists of the NMDA receptor with anti-depressant activity.

      Brown DG, Maier DL, Sylvester MA, Hoerter TN, Menhaji-Klotz E,   Lasota CC, Hirata LT, Wilkins DE, Scott CW, Trivedi S, Chen T,   McCarthy DJ, Maciag CM, Sutton EJ, Cumberledge J, Mathisen D,   Roberts J, Gupta A, Liu F, Elmore CS, Alhambra C, Krumrine JR,   Wang X, Ciaccio PJ, Wood MW, Campbell JB, Johansson MJ, Xia J,   Wen X, Jiang J, Wang X, Peng Z, Hu T, Wang J.

      Bioorg Med Chem   Lett. 2011 Jun 1;21(11):3399-403. doi:   10.1016/j.bmcl.2011.03.117. Epub 2011 Apr 8.

      Abstract:

        Herein we describe the discovery of compounds that are   competitive antagonists of the CP101-606 binding site within the   NR2B subtype of the NMDA receptor. The compounds identified do   not possess phenolic functional groups such as those in   ifenprodil and related analogs. Initial identification of hits in   this series focused on a basic, secondary amine side chain which   led to good potency, but also presented a hERG liability. Further   modifications led to examples of non-basic replacements which   demonstrated much less liability in this regard. Finally, one   compound in the series, 6a, was tested in the mouse forced swim   depression assay and found to show activity (s.c. 60   mg/kg).

      Address (URL): http://www.sciencedirect.com/science/article/pii/S0960894X10010826