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 were 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 properties of (R/S)-2a-d are also described. Analgesic activity was investigated by the hot plate test, also in the presence of selective antagonists of mu, delta and kappa opioid receptors. Preliminary analysis of the side-effects was also accomplished using the rota-rod test. Interesting antinociceptive activity was shown by all compounds and in particular by (R/S)-2a (AD50 = 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 compounds influenced locomotory activity to a much lesser extent than did morphine.
Collina
S
S
Dipartimento di Chimica Farmaceutica, Università di Pavia, Italy.
Azzolina
O
O
Vercesi
D
D
Barbieri
A
A
Lanza
E
E
Linati
L
L
Ghislandi
V
V
D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism
D000700:Analgesics; D009281:Naphthalenes; D011758:Pyrroles; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C013231:pyrroline