Novel AMPA and kainate receptor antagonists containing the pyrazolo[1,5-c]quinazoline ring system: Synthesis and structure–activity relationships

Abstract: This paper reports the synthesis and AMPA, Gly/NMDA, and KA receptor binding affinities of a new set of 1,9-disubstituted-8-chloro-pyrazolo[1,5-c]quinazoline-2-carboxylates 2–34. Binding data show that, in general, compounds 2–34 bind to the AMPA receptor with good affinity and selectivity. In particular, the obtained results indicate that the contemporary presence of a 1,2-dicarboxylic acid moiety and suitable benzo-substituents on the PQZ system is important to gain selective AMPA receptor antagonists. Moreover, this study shows that the presence of a 2-carboxybenzoylamino substituent at position-9 (compounds 33–34) is important for obtaining selective KA receptor antagonists. Some selected compounds were also tested for their functional antagonistic activity at both AMPA and NMDA receptor-ion channels. [Copyright &y& Elsevier]