- Inotropic, vasodilator and low Km, cAMP-selective, cGMP-inhibited phosphodiesterase (PDE III) inhibitory activities of 4a-methyl-4,4a-dihydro-5H-indenopyridazin-3(2H)-ones and 4a-methyl-4,4a,5,6-tetrahydrobenzocinnolin-3(2H)-ones
-
Novel 7-substituted-4,4a-dihydro-4a-methyl-5H-indenopyridazin-3-ones and 8-substituted-4a-methyl-benzocinnolin-3-ones have been synthesized and their PDE III inhibitory, inotropic and vasodilator potencies compared with those of their normethyl analogues and their bicyclic 4,5-dihydro-6-phenylpyridazinone analogues.The structure-activity relationships of the tricyclic pyridazinones differ from those of bicyclic pyridazinones mainly in respect of the effect of introducing the methyl group into the pyridazinone ring.Whilst in the4,5-dihydro-6-phenylpyridazin-3(2H)-ones, introduction of a 5-methyl group has been widely reported to lead to compounds of significantly greater potency, the novel tricyclic 4a-methylpyridazinones showed similar levels of inotropic, vasodilator and PDE III inhibitory potency to their normethyl analogues.Possible reasons for this difference in behaviour are discussed.
- Bakewell, S J,Coates, W J,Comer, M B,Reeves, M L,Warrington, B H
-
p. 765 - 774
(2007/10/02)
-
- Synthesis and biological evaluation of subsitituted benzo[h]cinnolinones and 3H-benzo[6,7]cyclohepta[1,2-c]pyridazinones: Higher homologues of the antihypertensive and antithrombotic 5H-indeno[1,2-c]pyridazinones
-
Several substituted benzo[h]cinnolinones 3 and 3H-benzo[6,7]cyclohepta[1,2-c]pyridazinones 4, which were designed as less rigid congeners of 5H-indeno[1,2-c]pyridazinones 2, were synthesized and tested as antihypertensive, inotropic, antithrombotic, antiinflammatory, and antiulcer agents. While the seven-membered ring derivatives displayed only antithrombotic properties, which were comparable to that of acetylsalicylic acid, most of the benzo[h]cinnolinones exhibited significant antihypertensive, inotropic, and antithrombotic properties. In this respect, the 8-amino (3b) and 8-acetylamino (3c) together with the 4,4a-dehydro analogue of 3c were found to possess the most potent and long-lasting antihypetensive activity. In particular, the dextro isomer of 3c was more active than the racemic form, with lower tachycadiac effects. Unlike the lower homologues 2, none of the compounds showed significant antiinflammatory or antiulcer activity.
- Cignarella,Barlocco,Pinna,Loriga,Curzu,Tofanetti,Germini,Cazzulani,Cavalletti
-
p. 2277 - 2282
(2007/10/02)
-
- Tricyclic dihydropyridazinones and pharmaceutical compositions containing them
-
The tricyclic dihydropyridazinone derivatives having formula I STR1 are endowed with interesting hypotensive, vasodilating, antiaggregant, antithrombotic and cytoprotective properties and are therefore useful in human or veterinary medicine.
- -
-
-