Details

Autor(en) / Beteiligte

• Piaz, Vittorio Dal
• Ciciani, Giovanna
• Turco, Giovanni
• Giovannoni, Maria Paola
• Miceli, Mauro
• Pirisino, Renato
• Perretti, Mauro

Titel

5-Acyl-6-aryl-4-nitro-3(2H)pyridazinones and Related 4-Amino Compounds: Synthesis and Pharmacological Evaluation

Ist Teil von

• Journal of pharmaceutical sciences, 1991-04, Vol.80 (4), p.341-348

Ort / Verlag

Washington: Elsevier Inc

Erscheinungsjahr

1991

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Several 4-nitro- and 4-amino-5-acyl-6-aryl-3(2H)pyridazinones were prepared and their in vitro and ex vivo antiaggregatory properties were evaluated. 4-Nitro derivatives 3 generally showed good activity in vitro towards arachidonic acid (AA)-induced human blood platelet aggregation. The 4-amino compound 4a, which has weak in vitro activity, exhibited antiplatelet activity, particularly on adenosine dephosphate (ADP)-induced aggregation ex vivo in rabbit. Moreover, the same compound was shown to be active in platelet-activating factors (PAF)- induced rat paw hyperalgesia and to be endowed with low acute oral toxicity. The 4-amino derivatives 4a–m and the other pyridazinones 5–9 administered orally to rats were also found to be more potent antiinflammatory agents than acetyl salicylic acid (ASA). Compounds 3a and 4a, tested in vitro on lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages, were seen to be active in the inhibition of prostaglandin E2 (PGE2) production and interleukin-1 activity. Structure–activity relationship studies in the series of antiaggregating pyridazinones 3 have shown the primary importance of the nitro and acetyl substituents at positions 4 and 5, respectively. Hydrophobic substituents at position 2 were also required for better activity.