Synthesis and pharmacological evaluation of 4,4a-dihydro-5H(1)benzopyrano(4,3-c)pyridazin-3(2H)ones bioisosters of antihypertensive and antithrombotic benzo(h)cinnolinones

A series of 4,4a-dihydro-5H-[1]benzopyrano[4,3-c]pyridazin-3-(2H)-ones (2a-h), have been prepared and evaluated for their pharmacological profile as antihypertensive and antithrombotic agents. Compounds 2 were ineffective in lowering the blood pressure of spontaneously hypertensive rats (SHR), only 2c (R1 = NHCOCH3) showing a short lasting action (< 2 h). Compounds 2c and 2b (R1 = NH2) were found to be very active as antithrombotic agents in mice, being more potent than acetylsalicylic acid (ASA) taken as reference drug. Moreover, many derivatives of this class protected rats from formation of ASA or phenylbutazone (PBZ) induced ulcers, the most active being 2f (R2 = OCH3) (ED50 = 12.2 mg/kg and 25.4 mg/kg po in ASA and PBZ models, respectively).