Rational Drug Design of δ Opioid Receptor Agonist TAN-67 from δ Opioid Receptor Antagonist NTI
作者： Hiroshi Nagase , Hideaki Fujii
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摘要: A highly selective nonpeptidic δ 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 was designed on the basis of message-address concept and accessory site theory. (−)-TAN-67 is a potent 1 shows strong antinociceptive, cardioprotective, antiarrhythmic effects. By contrast, (+)-TAN-67 induced hyperalgesia, opposite effect antinociception. An important intermediate ketone for TAN-67 synthesis, 8aR *)-4a-(3-methoxyphenyl)-2-methyl-6-oxodecahydroisoquinoline, has two structural features: trans-fused bicyclic heterocycle quaternary carbon stereocenter at bridgehead position. Syntheses reported by some research groups are described. The synthesis chiral TNA-67 also shown.
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