Investigation of phenolic bioisosterism in opiates: 3-sulfonamido analogues of naltrexone and oxymorphone.
[formula: see text] The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. On the basis of its putative role as a hydrogen-bonding donor in the interaction with opioid receptors, it was replaced with a sulfonamide group because of their similar pKa values. The first thebaine-derived 3-amino (8a, 8b) and subsequent sulfonamide analogues (10a, 10b) were synthesized from naltrexone (1a) and oxymorphone (1b) in a linear nine-step synthesis. The sulfonamides were tested in vitro and found inactive.
McCurdy
C R
CR
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
Jones
R M
RM
Portoghese
P S
PS
D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D009294:Narcotics / Q000138:chemical synthesis / Q000737:chemistry*; D010111:Oxymorphone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry*
D007202:Indicators and Reagents; D009294:Narcotics; D013449:Sulfonamides; D009271:Naltrexone; D010111:Oxymorphone