Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1

…, LM Doweyko, S Dugar, N Grazier, K Ngu…

Index: Ahmad; Doweyko; Dugar; Grazier; Ngu; Wu; Yost; Chen; Gougoutas; DiMarco; Lan; Gavin; Dorso; Serafino; Kirby; Atwal Journal of Medicinal Chemistry, 2001 , vol. 44, # 20 p. 3302 - 3310

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Citation Number: 49

Abstract

A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC50= 3.5 μM) shows inhibitory activity comparable to cariporide (IC50= 3.4 μM). Structure-activity relationships are used to optimize the affinity of various acyl ...