Back to Search
Start Over
Discovery of naldemedine: A potent and orally available opioid receptor antagonist for treatment of opioid-induced adverse effects.
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Jan2019, Vol. 29 Issue 1, p73-77. 5p. - Publication Year :
- 2019
-
Abstract
- Graphical abstract Highlights • We discovered a new chemotype, 7-carboxamide morphinan derivatives as opioid antagonist. • This chemotype is suitable for acting on peripherally. • From our results, compounds which have over 100 of PSA values are difficult to pass BBB. • Naldemedine showed dual actions in one dose, inhibiting constipation and nausea/vomiting induced by opioids. Abstract Structure-activity relationship studies of several morphinan derivatives were conducted to obtain dual antagonists for μ- and δ-opioid receptors. We discovered peripherally restricted dual antagonists for μ/δ-opioid receptors as a new chemotype with a morphinan scaffold, which are orally available and do not easily pass the blood–brain barrier. As we expected, some of these compounds inhibit opioid-induced constipation and emesis/vomiting with limited potential to interfere the analgesic effects of morphine. Among them, naldemedine was selected as a potential drug candidate. [ABSTRACT FROM AUTHOR]
- Subjects :
- *OPIOID abuse
*CARBOXAMIDES
*ANTICONVULSANTS
*OPIOID receptors
*MORPHINANS
Subjects
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 29
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 133498517
- Full Text :
- https://doi.org/10.1016/j.bmcl.2018.11.007