SYNTHESIS AND ANTIHYPERTENSIVE ACTIVITY OF 2,4-DIOXOIMIDAZOLIDIN-1-YLAND PERHYDRO-2,4-DIOXOPYRIMIDIN-1-YL ERGOLINE DERIVATIVES

The synthesis and antihypertensive activity of a series of 2,4-dioxoim idazolidin-1-yl and perhydro-2,4-dioxopyrimidin-1-yl ergoline derivati ves are reported. The oral antihypertensive activity was studied in sp ontaneously hypertensive rats (SHRs) by measuring systolic blood press ure 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 de rivatives devoid of side-effects related to the dopaminergic stimulati on and the importance of the Delta(9,10) double bond for conferring hi gh potency within these compounds. (C) 1998 Elsevier Science S.A. All rights reserved.