Antihypertensive ergolinepropionamides.
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.
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D010064:Embryo Implantation / Q000187:drug effects; D004873:Ergolines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011247:Pregnancy; D011388:Prolactin / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D004873:Ergolines; D011388:Prolactin