δオピオイド受容体作動薬, TAN-67の設計合成

抄録

A selective nonpeptidic δ opioid receptor agonist TAN-67, (4aS^*, 12 aR^*) -4 a- (3-hydroxyphenyl) -2-methyl-1, 2, 3, 4, 4 a, 5, 12, 12 a-octahydropyrido [3, 4-b] acridine was designed from the selective δ opioid receptor antagonist NTI on the basis of the message-address concept and the accessory site theory. (-) -TAN-67 is a potent and selective δ₁ opioid receptor agonist and showed profound antinociceptive effect, cardioprotective effect, and antiarrhythmic effect. On the contrary, (+) -TAN-67 induced hyperalgesia, which is the opposite effect of the antinociception. Optical resolution of racemic TAN-67 and the synthesis of (4aS^*, 8 aR^*) -4 a- (3-methoxyphenyl) -2-methyl-6-oxodecahydroisoquinoline, the important intermediate ketone of TAN-67 synthesis were also described.