Novel arylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides as inhibitors of platelet aggregation. 1. Synthesis and pharmacological evaluation.
A series of N-1-substituted derivatives of pyrazino[2,3-c][1,2, 6]thiadiazine 2,2-dioxides bearing aryl groups at the pyrazino moiety have been prepared. The synthesis involves ring formation between the diaminothiadiazine and suitable dicarbonyl compounds and subsequent introduction of the substituent at N-1. The compounds have been tested in vitro, as inhibitors of rabbit and human platelet aggregation, and ex vivo against rat platelet aggregation induced by arachidonic acid, ADP, collagen, U46619, and I-BOP. The results obtained indicate that some pyrazino[2,3-c][1,2, 6]thiadiazine derivatives show significant platelet aggregation inhibition similar to other antithrombotic agents and that the antiplatelet properties may be mediated by interference with the arachidonic acid pathway.
Campillo
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N
Instituto de Química Médica CSIC, Juan de la Cierva 3, 28006 Madrid, Spain, and Almirall Prodesfarma, S.A. Research Centre, Barcelona, Spain.
García
C
C
Goya
P
P
Páez
J A
JA
Carrasco
E
E
Grau
M
M
D000818:Animals; D003499:Cyclic S-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D003499:Cyclic S-Oxides; D010975:Platelet Aggregation Inhibitors; D013829:Thiadiazines