Structural analogues of some highly active non-competitive AMPA antagonists

Some 5-methyl analogues (14a–e) of the non-competitive AMPA antagonists 3-acylated 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-4,5-dihydro-3H-2,3-benzodiazepines (2,3) have been synthesized. Generally they show diminished or low biological activity but two derivatives (14a,b) reveal effects comparable to those of GYKI 52466 (1), the prototype non competitive AMPA antagonist. Scheme 1. (a) I2, Ag2O; (b) NaBH4; (c) p-NO2-C6H4-CHO, HCl, benzene; (d) O2, OH−; (e) R-NHNH2, cat. HCl; (f) MsCl, Et3N; (g) OH−; (h) RaNi, H2NNH2. Figure 1.