Ohmori, Junya; Kubota, Hirokazu; Shimizu-Sasamata, Masao; Okada, Masamichi; Sakamoto, Shuichi published the artcile< Novel α-Amino-3-hydroxy-5-methylisoxazole-4-propionate Receptor Antagonists: Synthesis and Structure-Activity Relationships of 6-(1H-Imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione and Related Compounds>, Name: 2-Amino-3-nitro-6-picoline, the main research area is azaquinoxalinedione AMPA receptor antagonist structure activity; imidazolyl pyridopyrazinedione preparation AMPA receptor antagonist.
The authors have synthesized and evaluated azaquinoxalinediones for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-substituted 2,3(1H,4H)-pyrido[2,3-b]pyrazinedione derivatives showed some differences in comparison with those of the corresponding substituted quinoxalinediones, including 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione (I) (YM90K). X-ray study showed that conformation of the 7-nitro group of I·HCl was nearly coplanar with the quinoxaline ring, whereas the 6-imidazol-1-yl group was rotated with respect to the aromatic ring. Binding studies indicated that the bulkiness of the 6-substituent on the pyridopyrazinediones may be responsible for the selectivity against the glycine site on the NMDA receptor. Among the azaquinoxalinediones tested, 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione (II) exhibited a combination of the best affinity to the AMPA receptor with a Ki value of 0.14 μM and selectivity against the glycine site (no affinity at 10 μM). In vivo, II also protected against sound-induced seizures in DBA/2 mice (min. ED, 10 mg/kg i.p.).
Journal of Medicinal Chemistry published new progress about Anticonvulsants. 21901-29-1 belongs to class pyridine-derivatives, and the molecular formula is C6H7N3O2, Name: 2-Amino-3-nitro-6-picoline.