摘要：

We have synthesized the nonpeptidic highly selective delta opioid receptor agonist, (+/-)-TAN-67, (4aS*, 12aR*)-4a-(3-hydroxyphenyl)-2-methyl-1,2,3,4,4a,5,12,12a-octahydropyrido [3,4-b] acridine. In spite of high potent agonist activity for the delta opioid receptor in in vitro assay, (+/-)-TAN-67 afforded no analgesic activity in the mouse warm-plate test. This result led us to separate (+/-)-TAN-67 into optically pure compounds. Each enantiomer of racemic TAN-67 was synthesized from the corresponding optically active 6-oxodecahydroisoquinoline which was obtained by fractional recrystallization of its optically pure di-p-toluoyl tartaric acid salt. In bioassay using mouse vas deferens, (-)-TAN-67 showed full agonist activity (IC50 = 3.65 nM). On the other hand, (+)-TAN-67 showed almost no agonist activity, but interestingly afforded hyperalgesic activity in vivo (i.t. injection).

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