Syntheses of novel high affinity ligands for opioid receptors.
Article Details
- CitationCopy to clipboard
Wentland MP, Lou R, Lu Q, Bu Y, Denhardt C, Jin J, Ganorkar R, VanAlstine MA, Guo C, Cohen DJ, Bidlack JM
Syntheses of novel high affinity ligands for opioid receptors.
Bioorg Med Chem Lett. 2009 Apr 15;19(8):2289-94. doi: 10.1016/j.bmcl.2009.02.078. Epub 2009 Feb 25.
- PubMed ID
- 19282177 [ View in PubMed]
- Abstract
A series of novel high affinity opioid receptor ligands have been made whereby the phenolic-OH group of nalbuphine, naltrexone methiodide, 6-desoxonaltrexone, hydromorphone and naltrindole was replaced by a carboxamido group and the furan ring was opened to the corresponding 4-OH derivatives. These furan ring 'open' derivatives display very high affinity for mu and kappa receptors and much less affinity for delta. The observation that these target compounds have much higher receptor affinity than the corresponding ring 'closed' carboxamides significantly strengthens our underlying pharmacophore hypothesis concerning the bioactive conformation of the carboxamide group.
DrugBank Data that Cites this Article
- Drugs
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Hydromorphone Kappa-type opioid receptor EC 50 (nM) 11 N/A N/A Details Hydromorphone Kappa-type opioid receptor Ki (nM) 2.8 N/A N/A Details Hydromorphone Mu-type opioid receptor EC 50 (nM) 2.6 N/A N/A Details Hydromorphone Mu-type opioid receptor Ki (nM) 0.28 N/A N/A Details Nalbuphine Kappa-type opioid receptor Ki (nM) 3 N/A N/A Details Nalbuphine Kappa-type opioid receptor EC 50 (nM) 56 N/A N/A Details Nalbuphine Mu-type opioid receptor IC 50 (nM) 96 N/A N/A Details Nalbuphine Mu-type opioid receptor EC 50 (nM) 46 N/A N/A Details Nalbuphine Mu-type opioid receptor Ki (nM) 1.6 N/A N/A Details