Synthesis and pharmacological evaluation of aminopyrimidine series of 5-HT 1A partial agonists

…, BM Campbell, T Crawford, L Denny, LM Evans…

Index: Dounay, Amy B.; Barta, Nancy S.; Bikker, Jack A.; Borosky, Susan A.; Campbell, Brian M.; Crawford, Terry; Denny, Lynne; Evans, Lori M.; Gray, David L.; Lee, Pil; Lenoir, Edward A.; Xu, Wenjian Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 4 p. 1159 - 1163

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Citation Number: 7

Abstract

Aminopyrimidine 2 (4-(1-(2-(1H-indol-3-yl) ethyl) piperidin-3-yl)-N-cyclopropylpyrimidin-2- amine) emerged from a high throughput screen as a novel 5-HT1A agonist. This compound showed moderate potency for 5-HT1A in binding and functional assays, as well as moderate metabolic stability. Implementation of a strategy for improving metabolic stability by lowering the lipophilicity (cLogD) led to identification of methyl ether 31 (4-(1-(2-(1H-indol-3-yl) ...