Probes for narcotic receptor mediated phenomena. 23.1 Synthesis, opioid receptor binding, and bioassay of the highly selective δ agonist (+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80) and related novel nonpeptide δ opioid receptor ligands

摘要: The highly selective delta (δ) opioid receptor agonist SNC 80 [(+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide, (+)-21] and novel optically pure derivatives were synthesized from the enantiomers of 1-allyl-trans-2,5-dimethylpiperazine (2). piperazine (±)-2 was synthesized, its obtained on a multigram scale in >99% optical purity by resolution racemate with camphoric acids. absolute configuration (+)-2 determined to be 2S,5R X-ray analysis salt (+)-camphoric acid. Since chirality starting material known, relative compounds (−)-21, (−)-22, (+)-23 single-crystal analysis, assignment stereochemistry entire series could made. Radioreceptor binding studies rat brain preparations showed that methyl ethers (+)-21 (SNC 80) (−)-25 exhibited strong selectivity for δ receptors low nanomola...