Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists
| Autor: | Shigeto Hirayama, Yusuke Iihara, Takashi Iwai, Hideaki Fujii, Toru Nemoto, Hiroshi Nagase, Eika Higashi |
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| Rok vydání: | 2015 |
| Předmět: |
Drug Inverse Agonism
Halogenation Stereochemistry medicine.drug_class Narcotic Antagonists Clinical Biochemistry Pharmaceutical Science Biochemistry Partial agonist Naltrindole Opioid receptor Receptors Opioid delta Drug Discovery medicine Humans Inverse agonist Receptor Molecular Biology Alkyl Binding affinities chemistry.chemical_classification Organic Chemistry Naltrexone Recombinant Proteins chemistry Opioid Molecular Medicine Enkephalin Leucine medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 25:2927-2930 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2015.05.038 |
| Popis: | We synthesized derivatives of the δ opioid receptor (DOR) antagonists naltrindole (NTI) and compound 1 that were modified with small alkyl or fluorinated ethyl substituents on the 17-nitrogen. Although the derivatives showed decreased binding affinities for the opioid receptors, their selectivities for the DOR were higher than the parent compounds NTI and compound 1. Surprisingly, 17-fluoroethyl NTI derivatives exerted DOR inverse agonistic activities. The DOR inverse agonism of compounds 4c–e was less efficacious but significant, as compared with a standard DOR inverse agonist ICI-174864. On the other hand, compound 1 and its derivatives with small alkyl or monofluoroethyl substituents were partial agonists, but the derivatives having di- or trifluoroethyl group showed neither agonistic nor inverse agonistic activities. |
| Databáze: | OpenAIRE |
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