ABSTRACT
The synthesis and the antihypertensive activity in rats of a series of 6-methylergolin-8 beta-yl-propionic acid derivatives are reported. The prolactin lowering activity (nidation inhibition test) in rats and the acute toxicity in mice were also studied as a measure of the specificity and safety of the potential antihypertensive compounds. From the structure-activity considerations reported here it is clear how modifications at the C8 side chain can improve the selectivity of the antihypertensive effects, whilst introducing substituents in other positions of the ergoline skeleton afforded unfavourable results in this respect. Compound 5, namely 2(R,S)-cyano-3-(6-methylergolin-8 beta-yl)-propionamide, emerged as the most interesting antihypertensive derivative.
Subject(s)
Antihypertensive Agents/chemical synthesis , Ergolines/chemical synthesis , Animals , Blood Pressure/drug effects , Chemical Phenomena , Chemistry , Embryo Implantation/drug effects , Ergolines/pharmacology , Ergolines/toxicity , Female , Lethal Dose 50 , Male , Mice , Pregnancy , Prolactin/antagonists & inhibitors , Rats , Rats, Inbred StrainsABSTRACT
The synthesis and the antitumor activities of a group of 4-demethoxy-4-alkoxydaunorubicins (VIII) are reported. The new compounds were found to have an activity equal or superior to that of daunorubicin, at somewhat higher doses.
