Alkylsquarates as key intermediates for the rapid preparation of original drug-inspired compounds |
| |
Authors: | Charton Julie Charruault Lise Deprez-Poulain Rebecca Deprez Benoit |
| |
Affiliation: | INSERM U761 Biostructures and Drug Discovery, F-59006 Lille, France. julie.charton@univ-lille2.fr |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|