An expeditious access to 5-pyrimidinol derivatives from cyclic methylglyoxal diadducts, formation of argpyrimidines under physiological conditions and discovery of new CFTR inhibitors. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2011

An expeditious access to 5-pyrimidinol derivatives from cyclic methylglyoxal diadducts, formation of argpyrimidines under physiological conditions and discovery of new CFTR inhibitors.

Résumé

In the study of previously reported modulators of CFTR chloride channels that are cyclic methylglyoxal (MG) diadducts (CMGD) to aromatic α-aminoazaheterocycles, we optimized a new expeditious one pot route for preparing in water novel aromatic polycyclic azaheterocycles and described 5-pyrimidinols antioxidants through the formation of 2-oxoaldehyde diadducts to aromatic α-aminoazaheterocycles, amidines, guanidines and thiourea. In regard to the importance as biomarkers of diabetic complications of the 5-pyrimidinols "argpyrimidines" formed in proteins from MG and arginine residues, we demonstrated that argpyrimidines are slowly formed under physiological conditions from CMGD to arginine derivatives according to the synthesis route described. Among the 5-pyrimidinol derivatives prepared, two polycyclic derivatives appeared to inhibit strongly the activity of CFTR channels in wt-CHO cells.

Dates et versions

hal-00582439 , version 1 (01-04-2011)

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Brice-Loïc Renard, Benjamin Boucherle, Bruno Maurin, Marie-Carmen Molina, Caroline Norez, et al.. An expeditious access to 5-pyrimidinol derivatives from cyclic methylglyoxal diadducts, formation of argpyrimidines under physiological conditions and discovery of new CFTR inhibitors.. European Journal of Medicinal Chemistry, 2011, 46 (5), pp.1935-41. ⟨10.1016/j.ejmech.2011.02.037⟩. ⟨hal-00582439⟩
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