Synthesis and pharmacological evaluation of novel selective MOR agonist 6β-pyridinyl amidomorphines exhibiting long-lasting antinociception
| Autor: | Ákos Urai, Levente Szőcs, Sándor Hosztafi, Balázs Komjáti, Amanda Hunkele, Gavril W. Pasternak, Valerie Le Rouzic, Susruta Majumdar, András Váradi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Analgesic Pharmaceutical Science Pharmacology Isonicotinic acid Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Drug Discovery medicine Potency Organic Chemistry 030104 developmental biology Nicotinic agonist chemistry Morphine Molecular Medicine Mitsunobu reaction 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | MedChemComm. 8:152-157 |
| ISSN: | 2040-2511 2040-2503 |
| DOI: | 10.1039/c6md00450d |
| Popis: | It was previously reported that 6β-aminomorphinan derivatives show high affinity for opiate receptors. Novel 6β-heteroarylamidomorphinanes were designed based on the MOR selective antagonist NAP. The 6β-aminomorphinanes were prepared by stereoselective Mitsunobu reaction and subsequently acylated with nicotinic acid and isonicotinic acid chloride hydrochlorides. The receptor binding and efficacy were determined in vitro and the analgesic activity was studied in vivo. The in vitro studies revealed moderate selectivity for the MOR. At least two compounds in this series exhibited a long-lasting analgesic response when administered subcutaneously and intracerebroventricularly. When the substances were given intracerebroventricularly to mice, they showed analgesic potency comparable to morphine. |
| Databáze: | OpenAIRE |
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