4-amino-5-substituted-3(2H)-pyridazinones as orally active antinociceptive agents: synthesis and studies on the mechanism of action.

doi:10.1021/JM070161E

Paper

4-amino-5-substituted-3(2H)-pyridazinones as orally active antinociceptive agents: synthesis and studies on the mechanism of action.

Published Jul 13, 2007 · M. Giovannoni, Nicoletta Cesari, C. Vergelli

Journal of medicinal chemistry

Q1 SJR score

24

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0

Influential Citations

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Abstract

A number of 4-amino-5-vinylpyridazinones and 4-amino-5-heterocyclic-pyridazinones were synthesized and tested for their analgesic activity. Many of these compounds, tested at doses of 3-20 mg kg-1 po, showed good antinociceptive activity, reducing by more than 50% the number of writhes with respect to controls. Compounds 16c, 19a, 20a, and 28 were the most potent of the series because they were able to induce a potent antinociceptive effect at a dose of 3 mg kg-1 po. None of the active compounds at the analgesic dose provoked any visible change in normal behavior, as demonstrated in the rotarod test. Studies on the mechanism of action showed that the analgesia induced by the active compounds was completely prevented by pretreatment with the alpha2-antagonist yohimbine, suggesting an involvement of alpha2-adrenoceptors. Further investigation demonstrated an indirect activation of the noradrenergic system through an amplification of noradrenaline release.

Non-RCT

Animal Study

Study Snapshot

Orally active 4-amino-5-substituted-3(2H)-pyridazinones show good analgesic activity, with compounds 16c, 19a, 20a, and 28 showing the most potent effects, suggesting involvement of alpha2-adrenoceptors and indirect

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

4-amino-5-substituted-3(2H)-pyridazinones as orally active antinociceptive agents: synthesis and studies on the mechanism of action.

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References

Citations

Visualization of poikilocytosis as an emerging erythrocytic biomarker for fish health assessment

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Isoxazolo[3,4-d] pyridazinones show potential as selective positive modulators of metabotropic glutamate receptors, with potential for hit-to-lead development.

Azolo[d]pyridazinones in medicinal chemistry.

Azolo[d]pyridazinone derivatives show diverse biological activities, including antidiabetic, antiasthmatic, anticancer, analgesic, anti-inflammatory, antithrombotic, antidepressant, and antimicrobial properties, making them a promising scaffold for drug development

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Isoxazolo[3,4-d]pyridazinones positively modulate the metabotropic glutamate subtypes 2 and 4.

Isoxazolo[3,4-d] pyridazinones selectively enhance metabotropic glutamate receptor subtypes 2 and 4, with no functional cross reactivity at other mGluRs.