Enzo Brambilla

Synthesis and nidation inhibitory activity of a new class of ergoline derivatives

Abstract The synthesis and the nidation inhibitory activity (indirect evidence of prolactin activity) of a new class of ergolinyl-acylureas is described. Some structure—activity relationship considerations are also reported. N -[3-(Dimethyl-amino)propyl]- N -[(ethylamino)carbonyl]-6-(2-propenyl)ergoline-8β-carboxamide (laboratory code FCE 21336; international non-proprietary name cabergoline) was the most interesting compound of the series and is now under extensive clinical evaluation in treatment of hyperprolactinemic disorders.

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.

An Easy Entry to (1S, 2S) and (1R, 2R)-Threo-Ifenprodil

Abstract A facile and practical synthesis of enantiomerically pure (L) or (D)-threo-Ifenprodil was accomplished from (1S, 2S)- and (1R, 2R)-threo-1-(p-nitrophenyl)-2-amino-propan-1, 3-diol via 3-phenylthio derivatives followed by Raney nickel reduction and conversion of the aromatic amine into phenol.

Synthesis and in vitro and in vivo evaluation of dopaminergic ergoline derivatives

A series of ergoline-amides was synthesised in the discovery of new dopaminomimetic agents. Several compounds exhibited in vivo high prolactin lowering activity (indirectly measured by the nidation test) in rats. For the most active, the potential anti-Parkinson activity was evaluated by observation of the contralateral turning behaviour in 6-OH-DA lesioned rats. The acute toxicity by oral route in mice was also studied.

5(10→9)Abeo-ergoline derivatives: Synthesis, 5-HT1A-receptor affinity and selectivity

Abstract The synthesis and the structure-affinity relationship (S.A.F.I.R.) study for the 5-HT 1A receptor sites of a novel series of 5(10→9) abeo -ergoline derivatives are presented. Most derivatives showed moderate to high affinity and selectivity for 5-HT 1A receptor sites. The structure-affinity relationship pointed out the role of the substituent at position 8, and the outstanding importance of the reduction of the indole 2,3-double bond for achieving the highest 5-HT 1A affinity and selectivity within the compounds presented.

(E) and (Z)-3-Styrylpiperidines as sigma ligands

Abstract A class of (E) and (Z)-3-styrylpiperidine derivatives was prepared as racemates and evaluated for affinity at σ binding sites labeled with [ 3 H]-(+)-SKF-10,047. Some of these compounds exhibited high affinity and selectivity for σ versus D 1 and D 2 binding sites.

Serotonergic ergoline derivatives

Novel classes of 13- and 14-tertbutyl-ergoline derivatives were prepared, and characterised in vitro for their affinity for adrenergic, dopaminergic and serotonergic binding sites. This study particularly examines the importance of the presence and the position of the tert-butyl group in conferring either significant 5-HT1A or 5-HT2 affinity and selectivity respectively.