Synthèse et évaluation de modulateurs de la protéine CFTR

Abstract : After the discovery of a new stereoselective reaction between methylglyoxal and α-aminoazaheterocycles in water under mild conditions leading to a new family of compounds (family I), some of the resulting compounds appeared to be able to modulate efficiently the Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Mutations of this protein which forms a cAMP-regulated chloride channel cause the severe genetic disease cystic fibrosis.
Small molecules able to modulate Cl– channels are interesting to understand the physiological role of these channels and also in the development of molecules of therapeutic interest. In the search for the chemical structure of the pharmacophore responsible for the observed effects in the active compounds (a positively charged nitrogen atom linked through two carbon atoms to a negatively charged oxygen atom), various compounds carrying or not the assumed pharmacophore were prepared and evaluated (compounds of families II and III prepared from compounds of the family I). Some of the prepared compounds were found to be interesting modulators of CFTR channels confirming the proposed structure of the pharmacophore.
Document type :
Chimie. Université Joseph-Fourier - Grenoble I, 2008. Français
Liste complète des métadonnées

Cited literature [123 references]  Display  Hide  Download
Contributor : Benjamin Boucherle <>
Submitted on : Monday, December 15, 2008 - 5:23:01 PM
Last modification on : Friday, February 16, 2018 - 9:44:01 AM
Document(s) archivé(s) le : Saturday, November 26, 2016 - 3:33:47 AM


  • HAL Id : tel-00347412, version 1



Benjamin Boucherle. Synthèse et évaluation de modulateurs de la protéine CFTR. Chimie. Université Joseph-Fourier - Grenoble I, 2008. Français. 〈tel-00347412〉



Record views


Files downloads