Synthesis and opioid activity of enantiomeric N-substituted 2,3,4,4a,5,6,7,7a-octahydro-1H-benzofuro[3,2-e]isoquinolines.
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Hsin LW, Chang LT, Rothman RB, Dersch CM, Fishback JA, Matsumoto RR
Synthesis and opioid activity of enantiomeric N-substituted 2,3,4,4a,5,6,7,7a-octahydro-1H-benzofuro[3,2-e]isoquinolines.
J Med Chem. 2010 Feb 11;53(3):1392-6. doi: 10.1021/jm901503e.
- PubMed ID
- 20055417 [ View in PubMed]
- Abstract
A series of enantiomeric N-substituted 2,3,4,4a,5,6,7,7a-octahydro-1H-benzofuro[3,2-e]isoquinolines was synthesized. The (-)-enantiomers had much greater kappa-, mu-, and delta-opioid receptor binding affinity than the corresponding (+)-enantiomers. Compounds (-)-1a, (-)-1b, and (-)-1c displayed subnanomolar binding affinity for the mu-receptor, and (-)-1b had a high affinity for the kappa-receptor. Compound (-)-1a was a mu-partial agonist and kappa-antagonist. Compound (-)-1b was a potent neutral mu-antagonist (K(d) = 0.22 nM) and a kappa-partial agonist.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Naloxone Kappa-type opioid receptor Ki (nM) 3 N/A N/A Details Naloxone Mu-type opioid receptor Ki (nM) 0.98 N/A N/A Details