Discovery of diaminobutane derivatives as Ca2+-permeable AMPA receptor antagonists Original Research Article

We designed and synthesized a series of the polyamine derivatives as potent Ca2+-permeable AMPA receptor antagonists. In the course of this study, we found that the polyamine derivatives exhibited strong hypotensive activity which was undesirable activity for neuroprotective agents. Therefore, we tried to find non-hypotensive antagonists by structural modification of such compounds. Through this derivatization, we obtained the diamine compounds having desired profiles. Especially, compound 8f, which was non-hypotensive and potent Ca2+-permeable AMPA receptor antagonist, showed neuroprotective effects in transient global ischemia models in gerbils.