Syntheses and opioid receptor binding properties of carboxamido-substituted opioids.

Article Details


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

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
DrugTargetKindOrganismPharmacological ActionActions
TramadolDelta-type opioid receptorProteinHumans
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ButorphanolKappa-type opioid receptorKi (nM)0.22N/AN/ADetails
ButorphanolKappa-type opioid receptorEC 50 (nM)2.9N/AN/ADetails
ButorphanolMu-type opioid receptorKi (nM)0.12N/AN/ADetails
ButorphanolMu-type opioid receptorIC 50 (nM)14N/AN/ADetails
NaloxoneKappa-type opioid receptorKi (nM)1.2N/AN/ADetails
NaloxoneMu-type opioid receptorKi (nM)0.66N/AN/ADetails
TramadolKappa-type opioid receptorKi (nM)14N/AN/ADetails
TramadolMu-type opioid receptorKi (nM)1600N/AN/ADetails