Modification of the furan ring of salvinorin A: Identification of a selective partial agonist at the kappa opioid receptor
| Autor: | William A. Carlezon, Cécile Béguin, Bruce M. Cohen, Thomas A. Munro, Lee-Yuan Liu-Chen, Wei Xu, Katharine K. Duncan, Douglas M. Ho |
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| Rok vydání: | 2009 |
| Předmět: |
Agonist
medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Biochemistry Partial agonist κ-opioid receptor Article Diterpenes Clerodane Structure-Activity Relationship chemistry.chemical_compound 5'-Guanidinonaltrindole Furan Drug Discovery medicine Furans Molecular Biology Salvinorin Receptors Opioid kappa Organic Chemistry Salvinorin A chemistry Opioid Molecular Medicine medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 17:1370-1380 |
| ISSN: | 0968-0896 |
| Popis: | In an effort to find novel agents which selectively target the kappa opioid receptor (KOPR), we modified the furan ring of the highly potent and selective KOPR agonist salvinorin A. Introduction of small substituents at C-16 was well tolerated. 12-epi-Salvinorin A, synthesized in four steps from salvinorin A, was a selective partial agonist at the KOPR. No clear SAR patterns were observed for C-13 aryl ketones. Introducing a hydroxymethylene group between C-12 and the furan ring was tolerated. Small C-13 esters and ethers gave weak KOPR agonists, while all C-13 amides were inactive. Finally, substitution of oxadiazoles for the furan ring abolished affinity for the KOPR. None of the compounds displayed any KOPR antagonism or any affinity for mu or delta opioid receptors. |
| Databáze: | OpenAIRE |
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