Synthesis and pharmacological study of 4,4a,5,6-tetrahydro-4a-substituted-benzo(h)cinnolin-3(2H)ones.
A series of 4,4a,5,6- tetrahydro-4a-substituted-benzo(h)cinnolin-3(2H)-one (II a-e) (III a) were synthesized and evaluated pharmacologically in comparison with the 4a-unsubstituted congeners (I), which were reported to be potent antithrombotic and antihypertensive agents. All the test compounds, apart from (II e) (R2 = OCH3) and (III a) (R1,R2 = H), displayed significant antihypertensive activity. In particular (II a) (R1,R2 = H) was more active than the unsubstituted analogue (I a). Moreover (II d) (R1 = OCH3), (II e) (R2 = OCH3) and (III a) showed antithrombotic activity comparable to or higher than that of ASA.
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Istituto Chimico Farmaceutico e Tossicologico, Università di Milano, Italy.
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D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D005343:Fibrinolytic Agents / Q000138:chemical synthesis*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010793:Phthalazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011724:Pyridazines / Q000138:chemical synthesis*; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D010793:Phthalazines; D011724:Pyridazines