title: Alkylsquarates as key intermediates for the rapid preparation of original drug-inspired compounds.
abstract: Many natural privileged scaffolds contain a basic nitrogen atom, which often is a key element of pharmacophore and a chemically reactive centre as well. In our ongoing research program devoted to the design of targeted libraries based on acidic templates, we developed methods to convert privileged basic compounds -like natural alkaloids or drugs into acidic compounds. This conversion led to a profound alteration of the pharmacophore, without changing the overall shape and lipophilicity of the molecule. We expect such modifications to generate unexpected biological activities. Recently, we focused on derivatives of squaric acid, a vinylogous carboxylic acid. Two series were studied. First we describe a new, selective parallel synthesis of squaramic acids from a dissymmetric diester (3-tert-butoxy-4-ethoxy-cyclobut-3-en-1,2-dione). This efficient procedure avoids the synthesis of the undesired squaramides. Secondly we describe a microplate parallel synthesis (15 micromol-scale) of squaric acid hydroxamate amides from a squaric hydroxamate ester.
authors.affiliation: INSERM U761 Biostructures and Drug Discovery, F-59006 Lille, France. julie.charton@univ-lille2.fr
authors.forename: Julie
authors.initials: J
authors.lastname: Charton
authors.forename: Lise
authors.initials: L
authors.lastname: Charruault
authors.forename: Rebecca
authors.initials: R
authors.lastname: Deprez-Poulain
authors.forename: Benoit
authors.initials: B
authors.lastname: Deprez
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003503:Cyclobutanes / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D006877:Hydroxamic Acids / Q000737:chemistry; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
chemical_list: D000588:Amines; D002614:Chelating Agents; D003503:Cyclobutanes; D004791:Enzyme Inhibitors; D004952:Esters; D006877:Hydroxamic Acids; D004364:Pharmaceutical Preparations; D010880:Piperidines; D054852:Small Molecule Libraries; C101250:diethyl squarate; D015032:Zinc; C030042:squaric acid