Synthesis and biological activity of some 3-amino compounds related to digoxigenin

3 alpha-Amino 1a and 3 beta-amino 1b analogues of digoxigenin 14 and their 12 beta-acetate derivatives 2a and 2b were prepared and tested for inotropic activity in the isolated guinea-pig atrial preparation. The 3 alpha-amino compounds were inactive whereas the 3 beta-amino compounds showed comparable activity to their 3 beta-hydroxy counterparts. The replacement of the 17 beta-butenolide ring by other ring systems was investigated. Compounds with a 3'-furyl ring, 9b and 16 were found to possess appreciable activity. A compound with a 4'-pyridazinyl ring 13b exhibited weak activity, whereas the isomeric butenolide compound 11b proved inactive. N-monomethylation of the amine 2b reduced activity and N-dimethylation abolished activity. Acetylation of the 12 beta-hydroxyl function gave less active compounds.