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Oxazines analogs, such as 25, were claimed as potentially effective against migraine and associated pain (48,49). Subsequently, a series of aminopyrimidines, e.g., 26, was disclosed that exhibited picomolar activity for the mGluRI receptor (IC5o value <1 nM) as well as activity against formalin-induced pain and in a migraine model of dural protein extravasion (50).

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