Identification of N-(2-(azepan-1-yl)-2-phenylethyl)-benzenesulfonamides as novel inhibitors of GlyT1

…, DE Wilkins, G Tian, G Jonak, X Wang, WM Potts…

Index: Varnes, Jeffrey G.; Forst, Janet M.; Hoerter, Tiffany N.; Holmquist, Christopher R.; Wilkins, Deidre E.; Tian, Gaochao; Jonak, Gerald; Wang, Xia; Potts, William M.; Wood, Michael W.; Alhambra, Cristobal; Brugel, Todd A.; Albert, Jeffrey S. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 16 p. 4878 - 4881

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Citation Number: 5

Abstract

A novel series of glycine transporter 1 (GlyT1) inhibitors is described. Scoping of the heterocycle moiety of hit 4-chlorobenzenesulfonamide 1 led to replacement of the piperidine with an azepane for a modest increase in potency. Phenyl sulfonamides proved superior to alkyl and non-phenyl aromatic sulfonamides, while subsequent ortho substitution of the 2- (azepan-1-yl)-2-phenylethanamine aromatic ring yielded 39 (IC50 37nM, solubility 14μM), ...