Synthesis and pharmacology of 8-amino-3-[ (tetrahydro-2-furanyl) methyl] benzomorphan
Zhou, Q.; Duan, W.-h.; Cohen, D.J.; Bidlack, J.M.; Wentland, M.P.
Yao Xue Xue Bao 38(10): 748-753
2003
ISSN/ISBN: 0513-4870 PMID: 14730897 Document Number: 552399
To design and synthesize new chiral 8-(substituted) amino-analogues of 3-[(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the structure-activity relationship (SAR) for 8-aminobenzomorphan. Target compounds were synthesized from the 8-triflate of the optically active 3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphans using Pd-catalyzed aminations. Opioid receptor binding experiments were performed to evaluate their biological activities. Both 8-amino and 8-phenylamino analogues showed lower binding affinity for mu, delta and kappa receptors than corresponding 8-hydroxy-3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphan in vitro. The relative poor binding affinity of the target compounds did not warrant conducting the in vivo studies to determine if they have the profile(kappa agonist/mu antagonist) that will be potentially useful in the treatment of drug addiction. Further study is in progress.