Document Detail

Probes for narcotic receptor mediated phenomena. 47. Novel C4a- and N-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.
MedLine Citation:
PMID:  23618710     Owner:  NLM     Status:  MEDLINE    
A series of N-methyl rac-cis-4a-aralkyl- and alkyl-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols have been prepared (2a-l) using a simple previously designed synthetic route, in order to find a ligand that would interact with both μ- and δ-opioid receptors. A C4a-phenethyl derivative 2a, was found to have modest receptor affinity both at μ- (K(i)=60 nM) and δ-opioid receptors (K(i)=64 nM). The N-methyl substituent of 2a and that of other ligands in the series was then modified to obtain compounds with different N-substituents that might provide higher affinity at both receptors. A number of compounds differently substituted at C4a and N were synthesized and evaluated. Binding studies and functional assays revealed a moderately selective δ-antagonist (2l), selective μ-δ antagonists (3d, 3g), and a μ-κ antagonist (3f).
Malliga R Iyer; Richard B Rothman; Christina M Dersch; Arthur E Jacobson; Kenner C Rice
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2013-04-03
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  21     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-10     Completed Date:  2013-12-03     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  3298-309     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ltd.
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MeSH Terms
CHO Cells
Cell Membrane / drug effects*,  metabolism
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
Molecular Structure
Narcotic Antagonists / chemical synthesis*,  chemistry,  pharmacology*
Pyridines / chemical synthesis*,  chemistry,  pharmacology
Receptors, Opioid, delta / antagonists & inhibitors*,  metabolism
Receptors, Opioid, kappa / antagonists & inhibitors*,  metabolism
Receptors, Opioid, mu / antagonists & inhibitors*,  metabolism
Structure-Activity Relationship
Sulfur Radioisotopes
Grant Support
Reg. No./Substance:
0/Ligands; 0/Narcotic Antagonists; 0/Pyridines; 0/Receptors, Opioid, delta; 0/Receptors, Opioid, kappa; 0/Receptors, Opioid, mu; 0/Sulfur Radioisotopes; 10028-17-8/Tritium; 37589-80-3/Guanosine 5'-O-(3-Thiotriphosphate)

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