González-Avión Xosé C, Mouriño Antonio, Rochel Natacha, Moras Dino
Departamento de Química Organica y Unidad Asociada al Consejo Superior de Investigaciones Científicas, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
J Med Chem. 2006 Mar 9;49(5):1509-16. doi: 10.1021/jm049016g.
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).
1α,25(OH)₂D₃在多种系统中的大量作用表明，维生素D核受体（VDR）配体在治疗炎症、皮肤病、骨质疏松症、癌症和自身免疫性疾病方面具有广泛的临床应用。为了在维持天然配体反式激活能力的同时减少高钙血症副作用，已合成了3000多种维生素D类似物。根据维生素D核受体（VDR）的晶体结构，通过收敛性维蒂希-霍纳方法合成了侧链连接在C-12位的新型激素1α,25(OH)₂D₃类似物。在所研究的化合物中，类似物2b对VDR表现出最高的结合亲和力，并且在瞬时转染试验中诱导VDR转录活性的效力最强（为天然配体反式激活活性的20%）。
