Identification and characterization of m4 selective muscarinic antagonists

Our interest in the area of m4 muscarinic antagonists has led us to study a series of benzoxazine isoquinolines. One of the most potent and selective compounds of this series is example 1 with an IC 50 value of 90.7nM at m4 receptors, and 72-fold (m1), 38-fold (m2), 10-fold (m3), and 82-fold (m5) more selective compared to the other receptors. The synthesis and receptor binding affinity of analogs of 1 are reported. The study of a series of benzoxazine isoquinolines, which led to the identification of a potent and selective m4 muscarinic antagonist 1 is reported. [For 1 at the m4 receptor, the IC 50 = 90.7 nM; however, 1 is 72-fold (m1), 38-fold (m2), 10-fold (m3), and 82-fold (m5) more selective when compared to the other receptors.]