| 19394821 |
Nguyen KT, Luethi E, Syed S, Urwyler S, Bertrand S, Bertrand D, Reymond JL: 3-(aminomethyl) piperazine-2,5-dione as a novel NMDA glycine site inhibitor from the chemical universe database GDB. Bioorg Med Chem Lett. 2009 Jul 15;19(14):3832-5. Epub 2009 Apr 10.
Docking of randomly selected compounds from the chemical universe database GDB-11, which contains all organic molecules up to 11 atoms of C, N, O, F possible under consideration of simple chemical stability and synthetic feasibility rules, into the NMDA receptor glycine site (1pb7.pdb) lead to the identification of 3-(aminomethyl) piperazine-2,5-dione 3 and its close analog 5-(aminomethyl) piperazine-2,3-dione 4 as possible new ligands for this drug target, which is implicated in synaptic plasticity, neuronal development, learning and memory. Synthesis of these compounds in 4 and 6 steps, respectively, and testing by radioligand displacement assays and electrophysiological measurements in Xenopus oocytes show that while 4 is inactive, 3 is indeed an inhibitor of glycine, with an estimated K (D) of 50 microM. |
31(0,1,1,1) |