Antonio Calogero Mulè

Tricyclic Pyrazoles. Part 1: Synthesis and Biological Evaluation of Novel 1,4-Dihydroindeno[1,2-c]pyrazol-based Ligands for CB1and CB2 Cannabinoid Receptors

Cannabinoids receptors, cellular elements of the endocannabinoid system, have been the focus of extensive studies because of their potential functional role in several important physiological and pathological processes. To further evaluate the properties of CB receptors, especially CB(1) and CB(2) subtypes, we have designed, using SR141716A as a benchmark, a new series of rigid 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides. Compounds 1 were synthesized from substituted 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxylic acids and requisite amines. The various analogues were assayed for binding both to the brain and peripheral cannabinoid receptors (CB(1) and CB(2)). Seven of the new compounds displayed very high in vitro CB(2) binding affinities, especially 1a, 1b, 1c, 1e, 1g, 1h and 1j which showed K(i) values of 0.34, 0.225, 0.27, 0.23, 0.385, 0.037 and 0.9 nM, respectively. Compounds 1a, 1b, 1c and 1h showed the highest selectivity for CB(2) receptor with K(i)(CB(1)) to K(i)(CB(2)) ratios of 6029, 5635, 5814 and 9810, respectively. Noticeably, 1h exhibited the highest affinity and selectivity for CB(2) receptors.

Pyridazine N-Oxides. III. Synthesis and “in vitro” antimicrobial properties of N-Oxide derivatives based on tricyclic indeno[2,1-c]pyridazine and benzo [f]cinnoline systems

A number of 9H‐indeno[2,1‐c]pyridazine N‐oxides (3a—c) and benzo[f]cinnoline N‐oxides (4,5a—c) have been synthesized and tested for antimicrobial activity. All new products were inactive against Gram negative bacteria and fungi. In contrast, among the compounds synthesized, 3b, 4b and 5b showed a moderate activity against Gram positive Staphylococcus aureus and Staphylococcus epidermidis. Of the present series, the 9‐nitro‐benzo[f]cinnoline N‐oxide 5b possessed the highest activity especially against Trichomonas vaginalis (MIC = 3.9 μg/ml).

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.