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Probes for narcotic receptor mediated phenomena. Part 42: synthesis and in vitro pharmacological characterization of the N-methyl and N-phenethyl analogues of the racemic ortho-c and para-c oxide-bridged phenylmorphans.

ABSTRACT: A new synthesis of N-methyl and N-phenethyl substituted ortho-c and para-c oxide-bridged phenylmorphans, using N-benzyl- rather than N-methyl-substituted intermediates, was used and the pharmacological properties of these compounds were determined. The N-phenethyl substituted ortho-c oxide-bridged phenylmorphan(rac-(3R,6aS,11aS)-2-phenethyl-2,3,4,5,6,11a-hexahydro-1H-3,6a-methanobenzofuro[2,3-c]azocin-10-ol (12)) was found to have the highest ?-opioid receptor affinity (K(i)=1.1 nM) of all of the a- through f-oxide-bridged phenylmorphans. Functional data ([³?S]GTP-?-S) showed that the racemate 12 was more than three times more potent than naloxone as an ?-opioid antagonist.

SUBMITTER: Kim JH 

PROVIDER: S-EPMC3115714 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Probes for narcotic receptor mediated phenomena. Part 42: synthesis and in vitro pharmacological characterization of the N-methyl and N-phenethyl analogues of the racemic ortho-c and para-c oxide-bridged phenylmorphans.

Kim Jin-Hee JH   Deschamps Jeffrey R JR   Rothman Richard B RB   Dersch Christina M CM   Folk John E JE   Cheng Kejun K   Jacobson Arthur E AE   Rice Kenner C KC  

Bioorganic & medicinal chemistry 20110422 11

A new synthesis of N-methyl and N-phenethyl substituted ortho-c and para-c oxide-bridged phenylmorphans, using N-benzyl- rather than N-methyl-substituted intermediates, was used and the pharmacological properties of these compounds were determined. The N-phenethyl substituted ortho-c oxide-bridged phenylmorphan(rac-(3R,6aS,11aS)-2-phenethyl-2,3,4,5,6,11a-hexahydro-1H-3,6a-methanobenzofuro[2,3-c]azocin-10-ol (12)) was found to have the highest μ-opioid receptor affinity (K(i)=1.1 nM) of all of th  ...[more]

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