title: Novel 1alpha,25-dihydroxyvitamin D3 analogues with the side chain at C12.
abstract: 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).
authors.affiliation: Departamento de Química Organica y Unidad Asociada al Consejo Superior de Investigaciones Científicas, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Xosé C
authors.initials: XC
authors.lastname: González-Avión
authors.forename: Antonio
authors.initials: A
authors.lastname: Mouriño
authors.forename: Natacha
authors.initials: N
authors.lastname: Rochel
authors.forename: Dino
authors.initials: D
authors.lastname: Moras
mesh_terms: D000818:Animals; D019556:COS Cells; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D020650:Combinatorial Chemistry Techniques; D003460:Crystallization; D006801:Humans; D008024:Ligands; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: C509701:20(17-12)-abeo-1,25-dihydroxy-24-dihomo-21-norvitamin D3; D008024:Ligands; D018167:Receptors, Calcitriol; D002117:Calcitriol