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.

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Kim JH, Deschamps JR, Rothman RB, Dersch CM, Folk JE, Cheng K, Jacobson AE, Rice KC

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.

Bioorg Med Chem. 2011 Jun 1;19(11):3434-43. doi: 10.1016/j.bmc.2011.04.028. Epub 2011 Apr 22.

PubMed ID

21570305 [ View in PubMed

]

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-metha nobenzofuro[2,3-c]azocin-10-ol (12)) was found to have the highest mu-opioid receptor affinity (K(i)=1.1 nM) of all of the a- through f-oxide-bridged phenylmorphans. Functional data ([(3)(5)S]GTP-gamma-S) showed that the racemate 12 was more than three times more potent than naloxone as an mu-opioid antagonist.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Morphine	Mu-type opioid receptor	Ki (nM)	2.6	N/A	N/A	Details