84264-88-0Relevant articles and documents
Identification of N-(2-(azepan-1-yl)-2-phenylethyl)-benzenesulfonamides as novel inhibitors of GlyT1
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.
scheme or table, p. 4878 - 4881 (2010/10/02)
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 37 nM, solubility 14 μM), the most potent GlyT1 inhibitor in this series. Favorable brain-plasma ratios were observed for select compounds in pharmacokinetic studies to evaluate CNS penetration.
