84264-88-0Relevant academic research and scientific papers
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.
THERAPEUTIC AGENTS
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Page/Page column 54-55, (2008/06/13)
A compound of the formula (I): wherein R1,R2,R3, R4,Ar, A, n and m are defined herein, is disclosed as a GlyT1 inhibitor; pharmaceutical compositions containing the compound of the formula (I) are also disclosed as are their use in medicine, for example in the treatment of schizophrenia.
