Novel superagonist analogs of 2-methylene calcitriol: Design, molecular docking, synthesis and biological evaluation

A new series of highly biologically active (20S,22R)-1α,25-dihydroxy-22-methyl-2-methylene-vitamin D₃ analogs, possessing different side chains, have been efficiently prepared as potential agents for medical therapy. Design of these synthetic targets was based on the analysis of the literature data and molecular docking experiments. The synthetic strategy involved Sonogashira coupling of the known A-ring dienyne with the C,D-ring enol triflates, obtained from the corresponding Grundmann ketones. All synthesized vitamin D compounds were characterized by high in vitro potency and, moreover, they proved to be very calcemic in vivo exerting high activity on bone with particularly elevated intestinal calcium transport.