Synthesis and antihypertensive activity of 2,4-dioxoimidazolidin-1-yl and perhydro-2,4-dioxopyrimidin-1-yl ergoline derivatives.
The synthesis and antihypertensive activity of a series of 2,4-dioxoimidazolidin-1-yl and perhydro-2,4-dioxopyrimidin-1-yl ergoline derivatives are reported. The oral antihypertensive activity was studied in spontaneously hypertensive rats (SHRs) by measuring systolic blood pressure by an indirect tail-cuff method at different times after treatment. The prolactin lowering activity (indirectly measured by the nidation test) in rats and the oral acute toxicity in mice were also studied. The results of this study revealed potent antihypertensive ergoline derivatives devoid of side-effects related to the dopaminergic stimulation and the importance of the delta 9,10 double bond for conferring high potency within these compounds.
Mantegani
S
S
Pharmacia and Upjohn, Nerviano, Milan, Italy.
Brambilla
E
E
Caccia
C
C
Chiodini
L
L
Ruggieri
D
D
Lamberti
E
E
Di Salle
E
E
Salvati
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004873:Ergolines / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D004873:Ergolines