Discovery of PF-00217830: Aryl piperazine napthyridinones as D 2 partial agonists for schizophrenia and bipolar disorder

…, HC Akunne, L Fitzgerald, K Nicholls, BJ Snyder…

Index: Johnson, Douglas S.; Choi, Chung; Fay, Lorraine K.; Favor, David A.; Repine, Joseph T.; White, Andrew D.; Akunne, Hyacinth C.; Fitzgerald, Lawrence; Nicholls, Kim; Snyder, Bradley J.; Whetzel, Steven Z.; Zhang, Liming; Serpa, Kevin A. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 9 p. 2621 - 2625

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Citation Number: 19

Abstract

The synthesis and structure–activity relationship (SAR) of a novel series of aryl piperazine napthyridinone D2 partial agonists is described. Our goal was to optimize the affinities for the D2, 5-HT2A and 5-HT1A receptors, such that the D2/5-HT2A ratio was greater than 5 to ensure maximal occupancy of these receptors when the D2 occupancy reached efficacious levels. This strategy led to identification of PF-00217830 (2) with robust inhibition of sLMA ...