Cardiac glycoside-like structure and function of 5 beta,14 beta-pregnanes.
5 beta-Reduction and 14 beta-substitution convert the planar progesterone molecule to the cardiac glycoside configuration--A and D rings of the steroid moiety are bent toward the alpha-face relative to the B and C rings. Potency of the 5 beta,14 beta-derivative in a [3H]ouabain binding assay or its ability to inhibit the sodium pump in red blood cells is enhanced by 3 beta-hydroxylation, 20 beta-hydroxylation, and 3 beta-glycosidation. Synthesis of 14,20 beta-dihydroxy-3 beta-(beta-D-glucopyranosyloxy)- 5 beta,14 beta-pregnane from digitoxin is described. The glucoside is 1/20 as potent as ouabain and elicits prominent, sustained, positive inotropy in isolated cardiac muscle.
Templeton
J F
JF
Kumar
V P
VP
Bose
D
D
LaBella
F S
FS
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000378:metabolism; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000378:metabolism / Q000494:pharmacology; D011278:Pregnanes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011955:Receptors, Drug / Q000378:metabolism; D012414:Rubidium Radioisotopes; D000254:Sodium-Potassium-Exchanging ATPase; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D011278:Pregnanes; D011955:Receptors, Drug; D012414:Rubidium Radioisotopes; C028996:cardiac glycoside receptors; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase