SYNTHESIS OF 20-HYDROXY-14-HYDROXY-21-NOR-5-BETA,14-BETA-PREGNANE, 20-AMINO-14-HYDROXY-21-NOR-5-BETA,14-BETA-PREGNANE, AND 20-NITRO-14-HYDROXY-21-NOR-5-BETA,14-BETA-PREGNANE C-3 GLYCOSIDES AND RELATED DERIVATIVES - STRUCTURE-ACTIVITY-RELATIONSHIPS OF PREGNANES THAT BIND TO THE DIGITALIS RECEPTOR

The preparation of derivatives of 14-hydroxy-21-nor-5beta,14beta-pregnane and 5beta,14beta-pregnane C-3 alpha-L-rhamnosides and tris-beta-D-digitoxosides is described. These derivatives, possessing a C-17beta 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 20alpha- and 20beta-pregnane analogs. The C-20 nitro rhamnoside is comparable to digitoxin in binding affinity. The 17beta-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.