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.
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis; D004076:Digoxigenin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004077:Digoxin / Q000031:analogs & derivatives*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D004077:Digoxin; D004076:Digoxigenin