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Rational Drug Design of δ Opioid Receptor Agonist TAN-67 from δ Opioid Receptor Antagonist NTI

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Bioactive Heterocycles II

Part of the book series: Topics in Heterocyclic Chemistry ((TOPICS,volume 8))

Abstract

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 the message-address concept and the accessory site theory. (−)-TAN-67 is a potent and selective δ 1 opioid receptor agonist and shows strong antinociceptive, cardioprotective, and antiarrhythmic effects. By contrast, (+)-TAN-67 induced hyperalgesia, the opposite effect of antinociception. An important intermediate ketone for the TAN-67 synthesis, (4aS *, 8aR *)-4a-(3-methoxyphenyl)-2-methyl-6-oxodecahydroisoquinoline, has two structural features: a trans-fused bicyclic heterocycle and a quaternary carbon stereocenter at the bridgehead position. Syntheses of the intermediate ketone reported by some research groups are described. The synthesis of chiral TNA-67 is also shown.

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Author information

Authors and Affiliations

  1. School of Pharmaceutical Science, Kitasato University, 5-9-1, Shirogane, Minatoku, Tokyo, Japan

    Hiroshi Nagase

  2. Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1, Tebiro, Kamakura, Kanagawa, Japan

    Hideaki Fujii

Authors
  1. Hiroshi Nagase
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  2. Hideaki Fujii
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Corresponding authors

Correspondence to Hiroshi Nagase or Hideaki Fujii .

Editor information

Shoji Eguchi

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© 2007 Springer-Verlag Berlin Heidelberg

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Nagase, H., Fujii, H. (2007). Rational Drug Design of δ Opioid Receptor Agonist TAN-67 from δ Opioid Receptor Antagonist NTI. In: Eguchi, S. (eds) Bioactive Heterocycles II. Topics in Heterocyclic Chemistry, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7081_2007_049

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