Synthesis and pharmacological evaluation of 4,4a,5,6-tetrahydro-7,8-disubstituted-benzo[h]cinnolin-3(2H)-ones.
7,8-disubstituted-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones 2-4 have been synthesized and tested in comparison with the 8-acetylamino-4,4a,5, 6-tetrahydrobenzo[h]cinnolin-3(2H)-one 1 reported to be a potent antihypertensive and antithrombotic agent. Binding studies on phosphodiesterase (PDE) isoenzymes showed that the test compounds exhibited a modest affinity towards PDE III which in the case of 2, 3 was higher than that of 1. In vivo tests indicated that compounds 2 and 4 displayed lower hypotensive activity than model 1 while 3 was inactive. Conversely, compounds 2-4 were as potent as 1 in inhibiting collagen-induced platelet aggregation.
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Istituto di Chimica Farmaceutica e Tossicologica, Sassari.
Loriga
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Curzu
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D'Amico
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D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D013764:Tetrahydronaphthalenes