Asymmetric syntheses, opioid receptor affinities, and antinociceptive effects of 8-amino-5,9-methanobenzocyclooctenes, a new class of structural analogues of the morphine alkaloids.

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Schultz AG, Wang A, Alva C, Sebastian A, Glick SD, Deecher DC, Bidlack JM

Asymmetric syntheses, opioid receptor affinities, and antinociceptive effects of 8-amino-5,9-methanobenzocyclooctenes, a new class of structural analogues of the morphine alkaloids.

J Med Chem. 1996 May 10;39(10):1956-66.

PubMed ID

8642554 [ View in PubMed

]

Abstract

Several 8-amino-5,9-methanobenzocyclooctenes have been prepared by asymmetric organic synthesis techniques. Opioid receptor affinity studies have revealed the virtual absence of enantioselectivity for receptor binding, particularly at the mu-receptor, for the (+)-3a-f and the (-)-3a-f series. It is noteworthy that inversion of configuration at the nitrogen-bearing carbon atom [5S,8S,9S)-8-amino-3-hydroxy-5, 9-methano-9-(methoxymethyl)-5-methylbenzocyclooctene, (+)-3a vs (5S,8S,9R)-8-amino-3-hydroxy-5, 9-methano-9-(methoxymethyl)-5-methylbenzocyclooctene, (dl)-22] resulted in a > 10-fold increase in kappa-receptor affinity. Antinociceptive studies demonstrated that (dl)-22 was a full kappa-agonist while (+)-3a and (-)-3a did not possess kappa-activity. Although both (dl)-22 and (+)-3a/(-)-3a had high affinity for the mu-receptor, these compounds did not act as high-affinity agonists or antagonists at this receptor.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Morphine	Kappa-type opioid receptor	Ki (nM)	330	N/A	N/A	Details