Cyclic guanidines: synthesis and antiplatelet activity of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo[3,4-d]pyrimidin-7-ones and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido[2,1-c] [1,2,4]triazin-7-ones.
A series of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo [3,4-d]pyrimidin-7-ones (1b-n) and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido [2,1-c][1,2,4]triazin-7-ones (2a-d) has been synthesized. In view of their potential anti-aggregating activity the compounds were tested in vitro for inhibitory activity towards ADP- and collagen-induced aggregation of human platelets. Among the compounds studied, 8-benzyl-1-(2,5-dichlorophenyl)-4,6,7,8-tetrahydro-1H-imidazo [1,2-a]pyrazolo[3,4-d]pyrimidin-7-one (1n) exhibited the most favorable activity. The 2,5-dichlorophenyl side chain is an important lipophilic and/or steric pharmacophore.
Ferroni
R
R
Dipartimento di Scienze Farmaceutiche dell'Università, Ferrara, Italy.
Simoni
D
D
Orlandini
P
P
Bardi
A
A
Franze
G P
GP
Guarneri
M
M
D000244:Adenosine Diphosphate / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D010976:Platelet Count; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology
D006146:Guanidines; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D011744:Pyrimidinones; D014227:Triazines; D000244:Adenosine Diphosphate; D003094:Collagen