Synthesis and antinociceptive activity of pyrrolidinylnaphthalenes Original Research Article

In this paper the synthesis of the racemates (2R,3S/2S,3R)-1,2-dimethyl-3-[2-(6-substituted naphthyl)]-3-hydroxypyrrolidine 1b–d [(2R,3S/2S,3R)-1b–d] are reported. Compounds 1b–d were prepared by reaction of the racemic 1,2-dimethyl-3-pyrrolidone 2 with the lithiation product obtained from 2-bromo-6-substituted naphthalene 3b–d. Pharmacological properties of (2R,3S/2S,3R)-1a–d are also described. Analgesic activity was investigated by the hot plate test and binding affinities towards μ, δ and κ opioid receptors were evaluated. A preliminary evaluation of the in vivo side-effects was also accomplished using the rota-rod test. Interesting antinociceptive activity was shown by all compounds and in particular by 1d, which is the most active compound, since it is six-fold more potent than morphine and has lower side effects on the locomotory activity.