Synthesis and pharmacological activity of 4-carbamoyl-6-beta-thienyl-4,5-dihydropyridazin-3-(2H)ones

A new series of 4-carbamoyl-6-beta-thienyl-4,5-dihydropyridazin-3-(2H)ones 4a-g have been synthesized and tested for their anti-inflammatory and analgesic properties. Among the tested compounds, only 4f at 1 mmole/Kg showed antiinflammatory activity that was comparable with that of indomethacin (5 mg/Kg) though of shorter duration. Compounds 4a, 4e and especially 4g at 0.2 mmoles/Kg displayed relevant analgesic activity, 4g being the most potent derivative in the writhing test. Compounds 4c and 4g were found to possess analgesic activity also in the hot plate test

Antihypertensive and antithrombotic activities of 6-(substitutedphenyl)-5-hydroxymethyl-4,5-dihydro-3(2H)pyridazinones

The synthesis of a series of 6-(4R-phenyl)-5-hydroxymethyl-4,5-dihydro-3(2H)pyridazinones is reported. The compounds were evaluated for their oral antihypertensive activity in rats and some of them [(V b), R = NH2] and [(V c), R = NHCOCH3] were found to induce a high decrease in systolic blood pressure. Moreover all the compounds displayed an antithrombotic activity comparable to, or greater than, that of ASA

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)

Rigid congeners of arylpyridazinones. IV. Synthesis and activity of derivatives of the new heterocyclic system 9H-indeno[2,1-c]pyridazine

Representative terms of the new heterocyclic system 9H-indeno[2,1-c]pyridazine have been synthesized. Their antiinflammatory, analgesic and antipyretic activities were evaluated, in order to compare the pharmacological profiles with those of the isomeric series of 5H-indeno[1,2-c]pyridazine previously investigated. The new compounds were, in general, equiactive as analgesic but less active as antiinflammatory and antipyretic agents with respect to their 5H-isomers

Behaviour of 5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one and 5,6-dihydrothieno[3,2-h]cinnolin-3(2H)-one towards hydrazine. Synthesis of thienocinnolinones and of 4-aminothienocinnolinones

The isomeric compounds 5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one (7a) and 5,6-dihydrothieno[3,2-h]cinnolin-3(2H)-one (7b) rapidly tautomerise to the corresponding 1,4-dihydrothienocinnolinones 8a,b when kept in refluxing hydrazine hydrate. With longer reaction times the initially formed 8a,b dehydrogenate to the thienocinnolinones 9a,b which eventually are aminated to 4-aminothienocinnolinones 10a,b. This behaviour recalls that reported for the related 5,6-dihydrobenzocinnolin-3(2H)-one (1) which under the same conditions undergoes dehydrogenation to bento[h]cinnolin-3 (2H)-one (2) followed by 4-amination to 3, but differs for the stability of the intermediates, for the mechanism of the final amination, and for the higher reaction rate. All these differences can be rationalised in terms of the heats of formation of the intermediates and products of the two series of transformations

Synthesis and pharmacological activity of 4-carbamoyl-5-aryl-6-methyl-4,5-dihydropyridazin-3(2H)ones

A new series of 4-carbamoyl-5-aryl-6-methyl-4,5-dihydropyridazin-3(2H)-ones have been synthesized and tested for their antiinflammatory and analgesic properties. Amongst the test compounds, only 31 showed antiinflammatory activity, though of shorter duration than that of indomethacin, taken as reference drug. On the contrary, many derivatives displayed relevant analgesic activity, 4 - the only 4,5-dehydroderivative - being the most potent in the writhing test. In the hot plate test 3b, 3f and 3k were found to possess the most significant analgesic properties

Synthesis and pharmacological study of 5-aryl-6-methyl-pyridazin-3(2H)ones and related 5-aryl-6-methylpyridazin-3(2H)ones

New 5-aryl-6-methyl-4,5-dihydropyridazin-3(2H)ones (III) and related 5-aryl-6-methyl-pyridazin-3(2H)ones (IV) were synthesized in order to evaluate their pharmacological profile in comparison with that of the known class of antihypertensive and platelet aggregation inhibitors 5-methyl-6-aryl-4,5-dihydropyridazin 3(2H)ones (I). Though none of the tested derivatives was found to possess the antihypertensive potency of the reference compounds, some of them displayed significant antithrombotic and antiulcer properties. In particular, 5(p. acetylaminophenyl)-6-methyl-pyridazin-3-one (IV c) was found highly effective (ED50 = 1.2 mg/kg) in inhibiting indomethacin-induced ulcers