Synthesis and antiplatelet activity of some 3-phenyl-1,8-naphthyridine derivatives.
A series of 2-cycloalkylamino-3-phenyl-1,8-naphthyridine derivatives, variously substituted in the 6- and 7-positions were synthesized and tested for their ability to inhibit human platelet aggregation in vitro induced by arachidonate, collagen and ADP. Compounds 5a,b, 7a,b, 8a and 10c,d showed a remarkable activity similar to that of indomethacin in the test with arachidonate and collagen. In the test with ADP only compound 8a showed a significant activity. The presence of a morpholinyl or piperidinyl group in position 2 and of a chloro or methoxy group in position 7 of the 1,8-naphthyridine nucleus seem to favour a higher activity. However on the basis of the pharmacological results, no structure-activity relationship can be deduced. Compounds 5b and 7b, which possess the best activity in the arachidonate test, were also shown to increase the c-AMP level significantly, without involving the adenylyl cyclase system.
Ferrarini
P L
PL
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy. ferrarini@farm.unipi.it
Mori
C
C
Badawneh
M
M
Franconi
F
F
Manera
C
C
Miceli
M
M
Saccomanni
G
G
D001792:Blood Platelets / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*
D009287:Naphthyridines; D010975:Platelet Aggregation Inhibitors