Conformationally restricted congeners of hypotensive and platelet aggregation inhibitors: 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones derived from 5H-indeno[1,2-c]pyridazine.
A number of 7-amino and 7-acylamino substituted 4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3-ones have been synthesized as rigid congeners of hypotensive 6-aryl-5-methyl-4,5-dihydro-3(2H)-pyridazinones and tested as antihypertensive, antithrombotic, antiulcer, and antiinflammatory agents. Unlike the previously described 7-cyano derivative, which displayed only antiinflammatory action, the new series exhibited significant antihypertensive and antithrombotic properties. In this respect, the 7-amino (2b) and the 7-acetylamino (2c) derivatives were found to be the most potent and long lasting in reducing the blood pressure in spontaneously hypertensive rats and in protecting mice from the induction of thrombosis. These compounds, as well as the 7-(2-chloropropionyl) derivative 2d, also exhibited antiinflammatory activity; in addition, 2c,d were highly effective in inhibiting indomethacin-induced ulcers in the rat.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000959:Antihypertensive Agents; D005343:Fibrinolytic Agents; D011724:Pyridazines