Synthesis and antinociceptive activity of pyrrolidinylnaphthalenes

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 Ib it were prepared by reaction of the racemic 1,2- dimethyl-3-pyrrolidone 2 with the lithiation product obtained frost 2-bromo -6-substituted naphthalene ne 3b d. Pharmacological properties of (2R.3S/2S ,3R)-1a-d are also described. Analgesic activity was investigated by the ho t plate test and binding affinities towards mu, delta and kappa opioid rece ptors were evaluated. A preliminary evaluation of the in vivo side-effects was also accomplished using the rots-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 ha s lower side effects on the locomotory activity. (C) 2000 Elsevier Science Ltd. All rights reserved.