Probes for narcotic receptor mediated phenomena. 40. N-substituted cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols
Iyer, M.R.; Lee, Y.S.; Deschamps, J.R.; Rothman, R.B.; Dersch, C.M.; Jacobson, A.E.; Rice, K.C.
Bioorganic and Medicinal Chemistry 18(1): 91-99
ISSN/ISBN: 1464-3391 PMID: 20005115 DOI: 10.1016/j.bmc.2009.11.022
A series of N-substituted rac-cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols have been prepared using a simple synthetic route previously designed for synthesis of related cis-2-methyl-4a-alkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols. The new phenolic compounds, where the aromatic hydroxy moiety is situated ortho to the oxygen atom in the oxide-bridged ring, do not interact as well as the pyridin-6-ols with opioid receptors. The N-para-fluorophenethyl derivative had the highest mu-opioid receptor affinity of the examined compounds (K(i)=0.35 microM).