Synthesis and structure–activity relationship studies of theophylline analogs on population responses in the rat hippocampus in vitro

We synthesized several theophylline analogs and tested the hypothesis that these compounds may be nootropic or cognitive enhancers by examining their effects on evoked population spikes recorded extracellularly in the CA1 region of the rat hippocampus. Whereas the length of the carbon chain on N7 had no effect, different size of the terminal lactam ring strongly influenced neuroactivity. Our results suggest that hexahydroazepin-2-one analogs have potential for further development as cognitive enhancers.

N7-substituted theophylline derivatives bearing various carbon chains (x = 1–3) and terminal lactam rings (y = 1–3) were synthesized and tested on hippocampal field population responses to see if they enhanced neuronal communication as possible nootropic agents.Figure optionsDownload as PowerPoint slide