Synthesis, binding affinity, and functional in vitro activity of 3-benzylaminomorphinan and 3-benzylaminomorphine ligands at opioid receptors.
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Neumeyer JL, Zhang B, Zhang T, Sromek AW, Knapp BI, Cohen DJ, Bidlack JM
Synthesis, binding affinity, and functional in vitro activity of 3-benzylaminomorphinan and 3-benzylaminomorphine ligands at opioid receptors.
J Med Chem. 2012 Apr 26;55(8):3878-90. doi: 10.1021/jm3001086. Epub 2012 Apr 4.
- PubMed ID
- 22439881 [ View in PubMed]
- Abstract
A series of 3-benzylamino-3-desoxymorphinan (I) and 3-benzylamino-3-desoxymorphine (II) derivatives were synthesized and evaluated for their binding affinities, and functional activity data are presented at MOR, KOR, and DOR. Some of these ligands were found to have high binding affinity at MOR and KOR and displayed increased selectivity at MOR over KOR and DOR compared to butorphan or cyclorphan. The most selective compound, 3-(3'-hydroxybenzyl)amino-17-methylmorphinan (4g) (24-fold MOR to KOR and 1700-fold MOR to DOR) also showed high binding affinity (0.42 nM to MOR) and was a full agonist in the [(35)S]GTPgammaS binding assay. 2-(3'-Hydroxybenzyl)amino-17-cyclopropylmethylmorphinan (17) was found to be a KOR-selective ligand (150-fold over MOR and >10000-fold over the DORs). Most 3-benzylaminomorphinan derivatives were partial agonists at MOR and full agonists at KOR in the [(35)S]GTPgammaS binding assay.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Hydrocodone Mu-type opioid receptor Ki (nM) 9.5 N/A N/A Details Levorphanol Kappa-type opioid receptor Ki (nM) 2.3 N/A N/A Details Levorphanol Mu-type opioid receptor Ki (nM) 0.21 N/A N/A Details Morphine Kappa-type opioid receptor Ki (nM) 24 N/A N/A Details Morphine Mu-type opioid receptor Ki (nM) 0.88 N/A N/A Details