Comparative Study of the Synthesis and Structural and Physicochemical Properties of Diketopiperazines vs Aza-diketopiperazines.
Fiche publication
Date publication
mars 2017
Journal
The Journal of organic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HIBERT Marcel, Dr BONNET Dominique
Tous les auteurs :
Regenass P, Bosc D, Riché S, Gizzi P, Hibert M, Karmazin L, Ganesan A, Bonnet D
Lien Pubmed
Résumé
Aza-diketopiperazines (aza-DKPs) represent an underprivileged motif obtained by scaffold hopping of 2,5-diketopiperazines (2,5-DKPs). Herein, we compare the synthesis and the structural and physicochemical properties of aza-DKP 4 vs 2,5-DKP 7. Thus, X-ray and (1)H NMR studies show that aza-DKP 4 is a rigid and nonflat scaffold like the 2,5-DKP 7. Moreover, the replacement of one Cα-stereogenic center by a nitrogen atom results in a significant improvement of both the water solubility and the microsomal stability.
Mots clés
Animals, Chromatography, Reverse-Phase, Crystallography, X-Ray, Mice, Microsomes, Liver, drug effects, Molecular Structure, Piperazines, chemical synthesis, Spectrum Analysis
Référence
J. Org. Chem.. 2017 Mar;82(6):3239-3244