1α,25-Dihydroxyvitamin D₃(1α,25-(OH)₂-D₃, 125D)is the most active metabolite of vitamin D₃, but the therapeutic application of 125D is limited by induction of hypercalcemia. The need for vitamin D compounds with selective biological profiles has stimulated the synthesis of more than three thousand analogues of 125D. This article reviews the recent progress of vitamin D research in the design and synthesis of the structural modifications in the A ring (including modification in the C2-, and C3-substitued, aromatic A ring and seco-A ring analogues), side chain, CD ring, seco-B ring, and non-secosteroidal vitamin D₃ analogs, and the relation between the structure and the biological activities.

Contents
1 Introduction
2 Structure-activity relationship of analogues modified in the A ring
2.1 Analogues modification of C-2-substitued
2.2 Aromatic A-ring 125D analogues
2.3 Ring-A-seco-19-nor analogues
2.4 C-3-subtitued-25-hydroxy analogues
3 Structure-activity relationship of analogues modified in the side chains
3.1 26-Desmethyl-2-methylene-22-ene-19-nor-analogues
3.2 C-22-oxa-analogues
3.3 Analogues with aromatic side chains attached at C-17
3.4 C-2 substituted analogues having ringed side chains
3.5 Analogues of combination of triple bond and adamantane ring on the side chain
4 Structure-activity relationship of analogues modified in CD-ring
4.1 13α-Substituted-des-C-ring-19-nor-125D analogues
4.2 Analogues with α-hydroxyalkyl substituents at C12
4.3 9-Alkylidene-19-nor-125D analogues with unnatural triene system
5 Structure-activity relation of analogues modified substituted in seco-B ring
5.1 6-Substituted analogues of 125D
5.2 C-7-methyl-19-nor-125D analogues
6 Structure-activity relationship of non-secosteroidal vitamin D analogues
6.1 Bis- and tris-aromatic analogues
6.2 p-Carborane-based non-secosteroidal vitamin D analogues
7 Conclusion and outlook