Cardiac glycoside(s) prepd. e.g. from canrenone - with a more potent positive inotropic effect than spironolactone or canrenone but without their undesirable side effects

摘要

Cardiac glycosides of formula (I) are new; the H or other substits. on C5 and/or C14 and the O on C17 can be alpha- or beta-; n = 1-2; R3 = - alpha or beta O; S-; NR1-alpha- n- or -beta-glucopyranosyl or furanosyl, the OH gps. of which are opt. replaced by O-alkyl, O-acyl, acetyl, ketal, halogen, pseudohalogen, azido, double bond, epoxide, O, NRa, NRaRb, or R3 = NRaSO2Rc; Rc = alkyl, cycloalkyl, aryl or aralkyl, opt. substd; R10, R13 = H, opt. substd. alkyl, ORa or CN; Ra, Rb, Rd and Re = H, OH, alkyl, cyclo alkyl, aryl, aralkyl or acyl, opt. substd.; H atoms on the steroid structure and for lactone ring are opt. replaced by ORa, SRa, NRaRb, O, NRa, CRaRb, N3, halogen, pseudohalogen, double bond, epoxide, acetal or ketal. Also new are derivs. of (I) in which the lactone ring is saponified to a hydroxy carboxylic acid in the form of its alkali, amine or ammonium salt (R+, Na+, HNRaRbRd+ or NRaRbRdRe+). USE/ADVANTAGE - (I) can be used in the therapy of latent and manifest cardiac insufficiency. (I) have a positive inotropic, more potent effect on the heart and circulation than spironolactone and canrenone but do not have their undesirable side effects. Thus (I) have greater therapeutic breadth. (I) act in a digitalis-like manner in the digitalis receptor enzyme system and yet do not cause digitalis-like intoxication.