Abstract
Active vitamin D3 (1Į,25-dihydroxyvitamin D3, 1,25(OH)2D3) is a biological endocrine factor that can express various biological actions, including calcium and bone metabolism, cell differentiation and proliferation, and immunoregulation. The multifunctional and potent biological activity of 1,25(OH)2D3 supports its clinical application in the treatment of many types of diseases, but it is widely accepted that the use of 1,25(OH)2D3 in clinic is limited by its primary side effect, hypercalcemia, which elevates the calcium level in serum. To discover a new drug that would overcome this problem, we studied the analogs of 1,25(OH)2D3 to discover one with the desired pharmacological effects and reduced side effects. From our study of these analogs, we discovered and developed the therapeutic agent for osteoporosis, eldecalcitol (1 Į,25-dihydroxy-2ȕ-(3-hydroxypropoxy)vitamin D3), which is characterized by the 3-hydroxypropoxy group introduced at the 2ȕ-position. Eldecalcitol exerts a significant therapeutic potency in osteoporosis treatment by preventing bone fracture and increasing bone mineral density. In this review, we will outline how eldecalcitol was discovered and explain its molecular mechanism of action from the viewpoint of medicinal chemistry.
