Novel 1alpha,25-dihydroxyvitamin D3 analogues with the side chain at C12.
Fiche publication
Date publication
mars 2006
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MORAS Dino
Tous les auteurs :
Gonzalez-Avion XC, Mourino A, Rochel N, Moras D
Lien Pubmed
Résumé
The plethora of actions of 1alpha,25(OH)2D3 in various systems suggested wide clinical applications of vitamin D nuclear receptor (VDR) ligands in treatments of inflammation, dermatological indication, osteoporosis, cancers, and autoimmune diseases. More than 3000 vitamin D analogues have been synthesized in order to reduce the calcemic side effects while maintaining the transactivation potency of the natural ligand. In light of the crystal structures of the vitamin D nuclear receptor (VDR), novel analogues of the hormone 1alpha,25(OH)2D3 with side chains attached to C-12 were synthesized via the convergent Wittig-Horner approach. Among the compounds studied, the analogue 2b showed the highest binding affinity for VDR and was the most potent at inducing VDR transcriptional activity in a transient transfection assay (20% of the transactivation activity of the natural ligand).
Référence
J Med Chem. 2006 Mar 9;49(5):1509-16.