Quinolizidinyl-benzimidazoles as platelet-antiaggregating agents.
Two series of (+/-)-2-phenyl-1-(quinolizidin-1 alpha-yl)benzimidazoles, 12A-26A, and (+/-)-2-phenyl-1-(quinolizidin-1 beta-yl)benzimidazoles, 12B-26B, were prepared and tested for the inhibition of human platelets aggregation induced by ADP, collagen, and adrenaline. All epimers A, i.e., 12A-26A, were devoid of any activity against the three agonists, while the epimers B, i.e., 12B-26B, exhibited different degrees of activity, though practically confined against the ADP-induced aggregation. The best compounds were 19B, 24B, and 26B, which inhibited for 69-67% at 260 microM and for 40-29% at 65 microM concentration the ADP (2 microM)-induced aggregation. The observed agonist and spatial structure selectivity warrant further investigations of this kind of benzimidazole derivatives.
Vazzana
Iana
I
Università di Genova, Dipartimento di Scienze Farmaceutiche, Viale Benedetto XV, 3, I-16132 Genova, Italy.
Terranova
Emanuela
E
Tasso
Bruno
B
Tonelli
Michele
M
Piana
Antonietta
A
Gastaldi
Stefanella
S
Sparatore
Fabio
F
D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects*; D054837:Quinolizidines / Q000737:chemistry*
D001562:Benzimidazoles; D054837:Quinolizidines