Research Of The Relationship Of Structure-activity Of Active Vitamin D Drugs And Synthesis Of Maxacalcitol

Active vitamin D3,known as1,25-(OH)2D3,is the active form of vitamin D3 in vivo.And it’s classical biological role is the maintenance of calcium homeostasis,also,it is a very important cell cycle regulator,and it has the activities of inducing the differentiation of malignant cells and inhibiting of cell proliferation.Vitamin D drugs have a variety of pharmacological effects,and are clinically used to treat inflammation,skin diseases,osteoporosis,cancer and immune diseases.Through the structural transformation,more than 3,000 active vitamin D3 derivatives have been synthesized so far.In this study,we summary the relationship between structures and activities of the active vitamin D3 molecules which have been reported in the literature,studying the quantitative structure-activity relationship(QSAR)of active vitamin D derivatives in 2D levels according to the changes in their structures,to discuss the trends of their activities,and establish the interaction mode of drugs and vitamin D receptor(VDR).Maxacalcitol(OTC),which contains an oxygen in place of carbon 22 of the side chain,was developped by Chugai in Japan in 2000 for the first time in practice,the injection is mainly used treatment for secondary hyperparathyroidism(SHPT),and the ointment for treatment of psoriasis.it is weaker in inhibiting parathyroid hormone(PTH)and regulating calcium level compared with calcitriol,so,long-term medication does not cause hypercalcemia.In this paper,a new route of synthesis maxacalcitol based on reported in the literature.Pregnenolone acetate is raw material,firstly reducted by NaBH4,then Williamson reaction,brominated-debromination to get the B ring intermediate of conjugated diene,and then photochemical and isomerization after de-acetyl group,at last,subjected to biotransformation which gives maxacalcitol.The new route of synthetic maxacalcitol designed by us is with a high yield,mild conditions of chemical reaction,easy to operate,so it made a experimental basis and foundation for factory production.More importantly,giving a backword for the study and subsequent production of active vitamin D3 analogs.