846031-35-4Relevant academic research and scientific papers
Discovery of PF-00217830: Aryl piperazine napthyridinones as D2 partial agonists for schizophrenia and bipolar disorder
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.
scheme or table, p. 2621 - 2625 (2011/06/20)
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 (MED = 0.3 mg/kg) and DOI-induced head twitches in rats (31% and 78% at 0.3 and 1 mg/kg) with no catalepsy observed at the highest dose tested (10 mg/kg).
