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J Med Chem. 1994 Jun 10;37(12):1886-8.

Synthesis and delta-opioid receptor antagonist activity of a naltrindole analogue with a regioisomeric indole moiety.

Author information

1
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.

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 approximately 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 delta-opioid receptor antagonist activity. It is proposed that the proper alignment of the benzene moiety with an address subsite on the delta receptor is critical for potent delta antagonist activity.

PMID:
8021929
DOI:
10.1021/jm00038a019
[Indexed for MEDLINE]

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