2-Alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT 2A antagonists

…, DA Rudolph, P Bonaventure, D Nepomuceno…

Index: Shireman, Brock T.; Dvorak, Curt A.; Rudolph, Dale A.; Bonaventure, Pascal; Nepomuceno, Diane; Dvorak, Lisa; Miller, Kirsten L.; Lovenberg, Timothy W.; Carruthers, Nicholas I. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 6 p. 2103 - 2108

Full Text: HTML

Citation Number: 8

Abstract

The synthesis and SAR for a novel series of 2-alkyl-4-aryl-tetrahydro-pyrido-pyrimidines and 2-alkyl-4-aryl-tetrahydro-pyrimido-azepines is described. Representative compounds were shown to be subtype selective 5-HT2A antagonists. Optimal placement of a basic nitrogen relative to the pyrimidine and the presence of a 4-fluorophenyl group in the pyrimidine 4- position was found to have a profound effect on affinity and selectivity.