Synthesis of pyrrolinylnaphthalenes and evaluation of their antinociceptive activity

In this paper the regioselective preparation of (R/S)-1,2-dimethyl-3-[2-(6- substituted naphthyl)]-2H,5H-pyrrolines 2a-d is reported. These compounds w ere prepared by thermal dehydration of the corresponding alcohols (2R,3S/2S ,3R)-1,2-dimethyl-3[2-(6-substituted naphthyl)]-3-hydroxy-pyrrolidines (2R, 3S/2S,3R)-1a-d with anhydrous FeCl3-SiO2, under vacuum. Pharmacological pro perties of (RIS)-2a-d are also described. Analgesic activity was investigat ed by the hot plate test, also in the presence of selective antagonists of mu, delta and kappa. opioid receptors. Preliminary analysis of the side-eff ects was also accomplished using the rota-rod test. Interesting antinocicep tive activity was shown by all compounds and in particular by (R/S)-2a (AD( 50) = 0.31 mg/kg); delta opioid receptors were found to be mainly involved in the pharmacological process and, in general, it was found that the compo unds influenced locomotory activity to a much lesser extent than did morphi ne. (C) 2000 Elsevier Science S.A. All rights reserved.