Probes for narcotic receptor-mediated phenomena. 27.1 Synthesis and pharmacological evaluation of selective δ-opioid receptor agonists from 4-[(αR)-α-(2S,5R)-4-substituted-2,5-dimethyl-1-piperazinyl-3-me thoxybenzyl]-N,N-diethylbenzamides and their enantiomers

M. S. Furness, X. Zhang, A. Coop, A. E. Jacobson, R. B. Rothman, C. M. Dersch, H. Xu, Frank Porreca, K. C. Rice

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Potent, selective, and efficacious δ-opioid receptor agonists such as (+)-4-[(αR)-α-(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl-3-meth oxybenzyl]-N,N-diethylbenzamide [SNC80, (+)-2] have been found to be useful tools for exploring the structural requirements which are necessary for ligands which interact with the δ-receptor. To determine the necessity for the 4-allyl moiety in (+)-2, this substituent was replaced with a variety of 4-alkyl, 4-arylalkyl, and 4-alkenyl substituents. The corresponding enantiomers of these compounds were also synthesized. The binding affinities for the μ-, δ-, and κ-opioid receptors and efficacies in the functional GTPγS binding assay were determined for the (+)-2 related compounds and their enantiomers. The 4-crotyl analogue was found to have similar δ-receptor affinity and efficacy as (+)-2, but the 4-cyclopropylmethyl analogue, in the functional assay, appeared to be a partial agonist with little antagonist activity.

Original languageEnglish (US)
Pages (from-to)3193-3196
Number of pages4
JournalJournal of Medicinal Chemistry
Issue number16
Publication statusPublished - Aug 10 2000


ASJC Scopus subject areas

  • Organic Chemistry

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