Click Chemistry Approach to New N-Substituted Aminocyclitols as Potential Pharmacological Chaperones for Gaucher Disease

• DOI: 10.1021/jm100198t
• Publication Date: 2010-06-17T13:42:39Z
• Authors: Lucía Díaz; Jordi Bujons; Josefina Casas; Amadeu Llebaria; Antonio Delgado
• Keywords: Moiety; Aminocyclitol; Triazole; Lipophilicity; Docking (animal); Molecular model

New N-alkylaminocyclitols bearing a 1,2,3-triazole system at different positions of the alkyl chain have been prepared as potential GCase pharmacological chaperones using click chemistry approaches. Among them, compounds 1d and 1e, with shorter spacer (n = 1) between alkyltriazolyl aminocyclitol core, were most active ones inhibitors, revealing determinant effect location triazole ring on activity. Furthermore, SAR data computational docking models indicate correlation lipophilicity enzyme inhibition suggest "extended" "bent" binding modes for compounds. In mode, could establish hydrogen-bond interaction moiety residue Q284. Such an would be precluded in longer core.