Synthesis and δ-Opioid Receptor Antagonist Activity of a Naltrindole Analogue with a Regioisomeric Indole Moiety

P. S. Portoghese, S. Ohkawa, S. T. Moe, A. E. Takemori

Research output: Contribution to journalComment/debatepeer-review

7 Scopus citations

Abstract

Indolomorphinans 2 and 3, in which the indole moiety is fused to the 7,8-position of the morphinan system, have been synthesized from dihydropseudocodeinone 4 and evaluated for antagonist activity on the mouse vas deferens (MVD) and guinea pig ileum (GPI) preparations. Indolomorphinan 2 was found to be ~ 1/60th as potent as naltrindole 1 in the MVD and an agonist in the GPI preparation. A comparable difference in affinity between 1 and 2 was observed. The methyl analogue 3 was inactive in both preparations. The results of this study support the idea that the regio orientation of the indolic benzene moiety of 1 is optimal for δ-opioid receptor antagonist activity. It is proposed that the proper alignment of the benzene moiety with an address subsite on the δ receptor is critical for potent δ antagonist activity.

Original languageEnglish (US)
Pages (from-to)1886-1888
Number of pages3
JournalJournal of medicinal chemistry
Volume37
Issue number12
DOIs
StatePublished - Jun 1 1994

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