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Elsevier, Bioorganic and Medicinal Chemistry, 19(23), p. 6237-6245

DOI: 10.1016/j.bmc.2015.08.043

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Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents

This paper is available in a repository.
This paper is available in a repository.

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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 20-40mg/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.