Synthesis of 20-hydroxy-, 20-amino-, and 20-nitro-14-hydroxy-21-nor- 5β,14β-pregnane C-3 glycosides and related derivatives: Structure-activity relationships of pregnanes that bind to the digitalis receptor

Article abstract of DOI:10.1021/jm00053a006

The preparation of derivatives of 14-hydroxy-21-nor-5β,14β-pregnane and 5β,14β-pregnane C-3 α-L-rhamnosides and tris-β-D-digitoxosides is described. These derivatives, possessing a C-17β COCH₂OH, CH₂OH, CO₂H, CO₂Me, CH₂NH₂, or CH₂NO₂ group, bind to the digitalis receptor recognition site of heart muscle as measured in a radioligand binding assay. The 21-norpregnane derivatives consistently show greater binding affinity than the corresponding 20α- and 20β-pregnane analogs. The C-20 nitro rhamnoside is comparable to digitoxin in binding affinity. The 17β-CH₂NO₂ group is the most effective replacement for the unsaturated lactone in the binding assay found so far, showing binding affinity comparable to that of the cardiac glycosides.