Essential Structure of Opioid κ Receptor Agonist Nalfurafine for Binding to κ Receptor 1: Synthesis of Decahydroisoquinoline Derivatives and Their Pharmacologies
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- Nagase Hiroshi
- School of Pharmacy, Kitasato University
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- Imaide Satomi
- School of Pharmacy, Kitasato University
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- Yamada Takaaki
- School of Pharmacy, Kitasato University
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- Hirayama Shigeto
- School of Pharmacy, Kitasato University
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- Nemoto Toru
- School of Pharmacy, Kitasato University
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- Yamaotsu Noriyuki
- School of Pharmacy, Kitasato University
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- Hirono Shuichi
- School of Pharmacy, Kitasato University
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- Fujii Hideaki
- School of Pharmacy, Kitasato University
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Abstract
On the basis of the three-dimensional pharmacophore model of opioid κ agonists, we simplified the structure of nalfurafine (selective κ agonist) to find the essential structural moieties for binding the opioid receptors, especially κ receptor type. As a result, we found that the trans-fused decahydroisoquinoline derivatives without a phenol ring bound the opioid receptor in micromolar order and that both the amide side chain and the nitrogen substituted by the cyclopropylmethyl group were indispensable moieties for eliciting the κ selectivity. The simple decahydroisoquinoline without amide side chain also bound the opioid receptor without receptor type selectivity, suggesting that the message-address concept would be applicable to even these simple derivatives. These findings that the simple decahydroisoquinoline derivatives showed the affinities for the opioid receptors, especially some of the compounds showed κ selectivity, are the first example in the opioid field.
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 60 (8), 945-948, 2012
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679154074880
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- NII Article ID
- 130001852522
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- NII Book ID
- AA00602100
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- COI
- 1:STN:280:DC%2BC38flsFWiug%3D%3D
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 023834338
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- PubMed
- 22863695
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed