CAS: 168123-82-8; 7-Bromopyrido[2,3-B]Pyrazine-2,3(1H,4H)-Dione

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2067-84-7 144435-08-5 25710-21-8

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5-bromo-pyridine-2,3-diamine oxalic acid 5-bromo-3-nitro-pyridin-2-ylamine oxalic acid diethyl ester

📜2-氨基-5-溴-3-硝基吡啶置于盐酸,Tin(Ll) Chloride体系中,用 乙醇 用作溶剂,化学反应 31.0H,反应生成7-溴吡啶并[2,3-B]吡嗪-2,3(1H,4H)-二酮
参考文献:5-(N-Oxyaza)-7-Substituted-1,4-Dihydroquinoxaline-2,3-Diones: Novel,Systemically Active And Broad Spectrum Antagonists For Nmda/glycine,Ampa,And Kainate Receptors
标题:5-(N-Oxyaza)-7-Substituted-1,4-Dihydroquinoxaline-2,3-Diones: Novel,Systemically Active And Broad Spectrum Antagonists For Nmda/glycine,Ampa,And Kainate Receptors
摘要:A Group Of 5-Aza-7-Substituted-1,4-Dihydroquinoxaline-2,3-Diones (Qxs) And The Corresponding 5-(N-Oxyaza)-7-Substituted Qxs Were Prepared And Evaluated As Antagonists Of Ionotropic Glutamate Receptors. The In Vitro Potency Of These Qxs Was Determined By Inhibition Of [h-3]-5,7-Dichlorokynurenic Acid ([h-3]Dcka) Binding To N-Methyl-D-Aspartate (Nmda)/glycine Receptors,[h-3]-(S)-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid ([h-3]Ampa) Binding To Ampa Receptors,And [h-3]Kainate ([h-3]Ka) Binding To Ka Receptors In Rat Brain Membranes. 5-(N-Oxyaza)-Qxs 12A-E All Have Low Micromolar Or Submicromolar Potency For Nmda/glycine Receptors And Low Micromolar Potencies For Ampa And Ka Receptors. Qxs 12A-E Display 2-12-Fold Selectivity For Nmda/glycine Receptors Compared To Ampa Receptors,And Similar To 2-Fold Difference Between Ampa And Ka Potency. In Contrast To Other Qxs That Either Show High Selectivity For Nmda (Such As Acea 1021) Or Ampa (Such As Nbqx) Receptors,These Molecules Are Broad Spectrum Antagonists Of Ionotropic Glutamate Receptors. 7-Nitro-5-(N-Oxyaza)-Qx (12E) Is The Most Potent Inhibitor Among 12A-E,Having Ic50 Values Of 0.69,1.3,And 2.4 Mu M At Nmda,Ampa,And Ka Receptors,Respectively. In Functional Assays On Glutamate Receptors Expressed In Oocytes By Rat Cerebral Cortex Poly(A(+)) Rna,7-Chloro-5-(N-Oxyaza)-Qx (12A) And 7-Nitro-5-(N-Oxyaza)-Qx (12E) Have K-B Values Of 0.63 And 0.31 Mu M For Nmda/glycine Receptors,And Are 6-And 4-Fold Selective For Nmda Over Ampa Receptors,Respectively. 5-(N-Oxyaza)-7-Substituted-Qxs 12A-E All Have Surprisingly High In Vivo Potency As Anticonvulsants In A Mouse Maximal Electroshock-Induced Seizure (Mes) Model. 7-Chloro-5-(N-Oxyaza)-Qx (12A),7-Bromo-5-(N-Oxyaza)-Qx (12B),And 7-Methyl-5-(N-Oxyaza)-Qx (12C) Have Ed50 Values Of 0.82,0.87,And 0.97 Mg/kg Iv,Respectively. The High In Vivo Potency Of Qxs 12A-E Is Particularly Surprising Given Their Low Log P Values (Similar To-2.7). Separate Studies Indicate That Qxs 12A And 12E Are Also Active In Vivo As Neuroprotectants And Also Have Antinociceptive Activity In Animal Pain Models. In Terms Of In Vivo Activity,These 5-(N-Oxyaza)-7-Substituted-Qxs Are Among The Most Potent Broad Spectrum Ionotropic Glutamate Antagonists Reported.
Doi:10.1021/jm970396Y