7-Spiroindanyl derivatives of naltrexone and oxymorphone as selective ligands for δ opioid receptors

S. Ohkawa; B. DiGiacomo; D. L. Larson; A. E. Takemori; P. S. Portoghese

doi:10.1021/jm9700880

7-Spiroindanyl derivatives of naltrexone and oxymorphone as selective ligands for δ opioid receptors

S. Ohkawa, B. DiGiacomo, D. L. Larson, A. E. Takemori, P. S. Portoghese

Medicinal Chemistry

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Abstract

A series consisting of spiroindanyl (5-7), benzospiroindanyl (8-10), and spiroperinaphthyl (11) derivatives of naltrexone and oxymorphone were synthesized in order to investigate the role of an orthogonal-oriented 'address' for δ opioid receptors. All of the ligands exhibited a preference for δ receptors in vitro. The 7-benzospiroindanyl derivative 8 (BSINTX) was the most selective δ opioid receptor antagonist in vitro. In mice BSINTX antagonized the δ₁-selective agonist, [D-Pen₂,D-Pen₅]enkephalin without significantly affecting the antinociceptive potency of δ₂, μ, and κ agonists. The results of this study are consistent with an orthogonally- oriented address favoring δ₁ activity.

Original language	English (US)
Pages (from-to)	1720-1725
Number of pages	6
Journal	Journal of medicinal chemistry
Volume	40
Issue number	11
DOIs	https://doi.org/10.1021/jm9700880
State	Published - May 23 1997

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AU - Ohkawa, S.

AU - DiGiacomo, B.

AU - Larson, D. L.

AU - Takemori, A. E.

AU - Portoghese, P. S.

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7-Spiroindanyl derivatives of naltrexone and oxymorphone as selective ligands for δ opioid receptors

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