Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents.
Basic Information
ID: ALA3612024
Journal: Bioorg Med Chem
Title: Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents.
Authors: Vergelli C, Ciciani G, Cilibrizzi A, Crocetti L, Di Cesare Mannelli L, Ghelardini C, Guerrini G, Iacovone A, Giovannoni MP.
Abstract: A number of heterocycles bearing an arylpiperazinylalkyl side chain and structurally related to the previously described lead ET1 (4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]-5-vinylpyridazin-3(2H)-one) was synthesized and tested for their antinociceptive activity in Writhing Test. Many compounds, tested at doses of 20-40 mg/kg po were able to reduce the number of abdominal constrictions by more than 47% and, in same cases, the potency is comparable to lead ET1 as for 5e, 24a, 27b and 27c. The analgesia induced by the active compounds was completely prevented by pretreatment with α2-antagonist yohimbine, confirming the involvement of the adrenergic system in the mechanism of action for these new compounds.
CiteXplore: 26361735
DOI: 10.1016/j.bmc.2015.08.043
Patent ID: ┄