1092822-63-3Relevant academic research and scientific papers
Probes for narcotic receptor mediated phenomena. 37.1 Synthesis and opioid binding affinity of the final pair of oxide-bridged phenylmorphans, the ortho- and para-b-isomers and their N-phenethyl analogues, and the synthesis of the N-phenethyl analogues of the ortho- and para-d-isomers
Kurimura, Muneaki,Liu, Hehua,Sulima, Agnieszka,Hashimoto, Akihiro,Przybyl, Anna K.,Ohshima, Etsuo,Kodato, Shinichi,Deschamps, Jeffrey R.,Dersch, Christina M.,Rothman, Richard B.,Yong, Sok Lee,Jacobson, Arthur E.,Rice, Kenner C.
, p. 7866 - 7881 (2008)
In the isomeric series of 12 racemic topologically rigid N-methyl analogues of oxide-bridged phenylmorphans, all but two of the racemates, the ortho- and para-b-oxide-bridged phenylmorphans 20 and 12, have remained to be synthesized. The b-isomers were very difficult to synthesize because of the highly strained 5,6-transfused ring junction that had to be formed. Our successful strategy required functionalization of the position para (or ortho) to a fluorine atom on the aromatic ring using an electron-withdrawing nitro group to activate that fluorine. The racemic N-phenethyl analogues 24 and 16 were moderately potent κ-receptor antagonists in the [35S]GTPγS assay. We synthesized the N-phenethyl-substituted oxide-bridged phenylmorphans in the ortho- and para-d-oxide-bridged phenylmorphan series (51 and 52) which had not been previously evaluated using contemporary receptor binding assays to see whether they also have higher affinity for opioid receptors than their N-methyl relatives 46 and 47.
