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Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock. Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.

A domino reaction of vinyl malononitriles (VMs) with 1,2-diaza-1,3-dienes (DDs) produce unprecedented 3a,4-dihydro-1H-pyrrolo[1,2-b]pyrazole systems in a chemo-, regio-, and stereoselective fashion. This base promoted (DIPEA) one-pot transformation involving multiple steps constructs one new C-C bond, two C-N bonds, and two new fused heterocyclic rings with total atom economy.

Synthesis of Densely Functionalized 3a,4-Dihydro-1H-pyrrolo[1,2-b]pyrazoles via Base Mediated Domino Reaction of Vinyl Malononitriles with 1,2-Diaza-1,3-dienes. -A domino reaction of 1,2-diaza-1,3-dienes with vinyl malonitriles produces unprecedented 3a,4-dihydro-1H-pyrrolo[1,2-b]pyrazoles in a chemo-and regioselective fashion. This base-promoted one-pot transformation constructs one new C-C bond, two C-N bonds, and two new fused heterocyclic rings with total atom economy. No information are given about the relative configuration in 3a,4-disubstituted products (VII). -(ATTANASI, O. A.; FAVI*, G.; GERONIKAKI, A.; MANTELLINI, F.; MOSCATELLI, G.; PAPARISVA, A.; Org. Lett. 15 (2013) 11, 2624-2627, http://dx.