Essential structure of opioid κ receptor agonist nalfurafine for binding to the κ receptor 2: Synthesis of decahydro(iminoethano)phenanthrene derivatives and their pharmacologies
| Autor: | Shigeto Hirayama, Hideaki Fujii, Satomi Imaide, Toru Nemoto, Hiroshi Nagase |
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| Rok vydání: | 2012 |
| Předmět: |
Agonist
medicine.drug_class Stereochemistry Clinical Biochemistry Cyclohexene Pharmaceutical Science Ring (chemistry) Biochemistry chemistry.chemical_compound Amide Cyclohexenes Drug Discovery medicine Side chain Moiety Spiro Compounds Molecular Biology Receptors Opioid kappa Organic Chemistry Phenanthrenes Morphinans chemistry Opioid Molecular Medicine Nalfurafine Protein Binding medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:5071-5074 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2012.05.122 |
| Popis: | To clarify the essential structures of an opioid κ receptor selective agonist, nalfurafine, for binding to the κ receptor, we designed and synthesized some nalfurafine derivatives and the decahydro(iminoethano)phenanthrene derivatives with a cyclohexene moiety as a surrogate for the phenol ring. In addition to the 6-amide side chain and the 17-nitrogen substituted by a cyclopropylmethyl group, the 4,5-epoxy ring, phenolic hydroxy group, and angular hydroxy group played important roles in eliciting the binding properties of nalfurafine but these three moieties were not indispensable for binding to the κ receptor. Moreover, the phenol ring was also not essential for the binding to the κ receptor, and the cyclohexene moiety would play an important role in fixing the conformation of decahydro(iminoethano)phenanthrene derivatives to effectively raise the amide side chain, rendering a conformation that resembled the active one of nalfurafine. |
| Databáze: | OpenAIRE |
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