Probes for narcotic receptor mediated phenomena. 39. Enantiomeric N-substituted benzofuro[2,3-c]pyridin-6-ols: synthesis and topological relationship to oxide-bridged phenylmorphans.
Enantiomers of N-substituted benzofuro[2,3-c]pyridin-6-ols have been synthesized, and the subnanomolar affinity and potent agonist activity of the known racemic N-phenethyl substituted benzofuro[2,3-c]pyridin-6-ol can now be ascribed to the 4aS,9aR enantiomer. The energy-minimized structures suggest that the active enantiomer bears a greater three-dimensional resemblance to morphine than to an ostensibly structurally similar oxide-bridged phenylmorphan. Structural features of the conformers of N-substituted benzofuro[2,3-c]pyridin-6-ols were compared to provide the rationale for their binding affinity.
Zhang
Yi
Y
Department of Health and Human Services, Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-9415, USA.
Lee
Yong Sok
YS
Rothman
Richard B
RB
Dersch
Christina M
CM
Deschamps
Jeffrey R
JR
Jacobson
Arthur E
AE
Rice
Kenner C
KC
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009019:Morphinans / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011789:Quantum Theory; D011957:Receptors, Opioid / Q000378:metabolism*; D013237:Stereoisomerism
D009019:Morphinans; D010087:Oxides; D011725:Pyridines; D011957:Receptors, Opioid; C042531:phenylmorphan; D009584:Nitrogen