Syntheses and opioid receptor binding properties of carboxamido-substituted opioids.
Article Details
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Wentland MP, Lou R, Lu Q, Bu Y, VanAlstine MA, Cohen DJ, Bidlack JM
Syntheses and opioid receptor binding properties of carboxamido-substituted opioids.
Bioorg Med Chem Lett. 2009 Jan 1;19(1):203-8. doi: 10.1016/j.bmcl.2008.10.134. Epub 2008 Nov 7.
- PubMed ID
- 19027293 [ View in PubMed]
- Abstract
A series of 15 novel opioid derivatives were made where the prototypic phenolic-OH group of traditional opioids was replaced by a carboxamido (CONH(2)) group. For 2,6-methano-3-benzazocines and morphinans similar or, in a few instances, enhanced affinity for mu, delta and kappa opioid receptors was observed when the OH-->CONH(2) switch was applied. For 4,5alpha-epoxymorphinans, binding affinities for the corresponding carboxamide derivatives were much lower than the OH partner consistent with our pharmacophore hypothesis concerning carboxamide bioactive conformation. The active metabolite of tramadol and its carboxamide counterpart had comparable affinities for the three receptors.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Tramadol Delta-type opioid receptor Protein Humans UnknownAgonistDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Butorphanol Kappa-type opioid receptor Ki (nM) 0.22 N/A N/A Details Butorphanol Kappa-type opioid receptor EC 50 (nM) 2.9 N/A N/A Details Butorphanol Mu-type opioid receptor Ki (nM) 0.12 N/A N/A Details Butorphanol Mu-type opioid receptor IC 50 (nM) 14 N/A N/A Details Naloxone Kappa-type opioid receptor Ki (nM) 1.2 N/A N/A Details Naloxone Mu-type opioid receptor Ki (nM) 0.66 N/A N/A Details Tramadol Kappa-type opioid receptor Ki (nM) 14 N/A N/A Details Tramadol Mu-type opioid receptor Ki (nM) 1600 N/A N/A Details