Design, synthesis and structure–activity relationship (SAR) studies of 2, 4-disubstituted pyrimidine derivatives: Dual activity as cholinesterase and Aβ-aggregation …

T Mohamed, X Zhao, LK Habib, J Yang…

Index: Mohamed, Tarek; Zhao, Xiaobei; Habib, Lila K.; Yang, Jerry; Rao, Praveen P.N. Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 7 p. 2269 - 2281

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Citation Number: 29

Abstract

A novel class of 2, 4-disubstituted pyrimidines (7a–u, 8a–f, 9a–e) that possess substituents with varying steric and electronic properties at the C-2 and C-4 positions, were designed, synthesized and evaluated as dual cholinesterase and amyloid-β (Aβ)-aggregation inhibitors. In vitro screening identified N-(naphth-1-ylmethyl)-2-(pyrrolidin-1-yl) pyrimidin-4- amine (9a) as the most potent AChE inhibitor (IC50= 5.5 μM). Among this class of ...