2-Pyridylarylhydrazone derivatives, a new class of platelet aggregation inhibitors.
A series of 2-pyridylarylhydrazone derivatives was synthesized and compared with a previously reported pyrazole series, i.e., 4-acylpyrazolylarylhydrazone and 5-pyrazolylarylhydrazone, which present antiplatelet aggregation activity. The structures of these pyridylarylhydrazone derivatives were designed on the basis of the known bioisosteric relationship of the heteroaromatic ring. The antiplatelet aggregation activity was measured in vitro on citrated platelet-rich rabbit plasma in which aggregation was induced with 5 microM ADP, 5 micrograms/ml collagen and 200 microM arachidonic acid. Eighteen compounds belonging to the pyridine series were tested at 1 mM concentration and none inhibited ADP-induced rabbit platelet aggregation. 2-(2-Formylfurane)pyridylhydrazone exhibited a highly potent inhibitory activity on arachidonic acid-induced aggregation, with an IC50 of 0.35 microM. These results suggest that the hydrazone unit and the 2-furyl moiety of the arylhydrazone framework are important pharmacophores for antiplatelet activity.
Todeschini
A R
AR
Laboratório de Avaliação e Síntese de Substâncias Bioativas, Universidade Federal do Rio de Janeiro, Brasil.
Miranda
A L
AL
Bacha
C M
CM
Barreiro
E J
EJ
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000031:analogs & derivatives* / Q000737:chemistry; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits
D010975:Platelet Aggregation Inhibitors; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine