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.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics, Opioid / chemical synthesis*
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Analgesics, Opioid / chemistry
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Analgesics, Opioid / pharmacology*
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Animals
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Binding Sites
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Brain / drug effects
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CHO Cells
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Cricetinae
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Cricetulus
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Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology*
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Molecular Structure
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Rats
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Receptors, Opioid / chemistry
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Receptors, Opioid / metabolism*
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Receptors, Opioid, kappa / chemistry
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Receptors, Opioid, kappa / metabolism*
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Receptors, Opioid, mu / chemistry
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Receptors, Opioid, mu / metabolism*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Analgesics, Opioid
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Isoquinolines
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Receptors, Opioid
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Guanosine 5'-O-(3-Thiotriphosphate)