Synthesis, platelet aggregation inhibitory activity, and in vivo antithrombotic activity of new 1,4-dihydropyridines.
A series of 1,4-dihydropyridines (DHP) bound to 1,2-benzisothiazol-3-ones were synthesized and evaluated for their ability to inhibit platelet aggregation induced by collagen in human platelet-rich plasma (PRP) and to protect mice against experimental thrombosis. The results showed that the compounds were in vitro inhibitors of collagen-induced platelet aggregation. Most of them were also effective in reducing mortality in the mouse antithrombotic assay. 2-(1,1,3-Trioxo-2,3-dihydro-1,2-benzisothiazol-2-yl)ethyl 2,6-dimethyl-5-(ethoxycarbonyl)-4-methyl-1,4-dihydropyridinecarboxyla te (4A) is the most promising compound. This compound did not show any cardiovascular effects either in the anesthetized cat or in the anesthetized rat at iv doses up to 750 or 500 micrograms/kg, respectively. Likewise, antiplatelet and cardiovascular effects of compound 4A were simultaneously studied in anesthetized rats and compared with those of nitrendipine.
Sunkel
C E
CE
ALTER, S.A. Research Department, Madrid, Spain.
Fau de Casa-Juana
M
M
Cillero
F J
FJ
Priego
J G
JG
Ortega
M P
MP
D000818:Animals; D002415:Cats; D003094:Collagen / Q000494:pharmacology; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D009568:Nitrendipine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000517:prevention & control*
D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D003094:Collagen; D009568:Nitrendipine