Syntheses of novel high affinity ligands for opioid receptors.
A series of novel high affinity opioid receptor ligands have been made whereby the phenolic-OH group of nalbuphine, naltrexone methiodide, 6-desoxonaltrexone, hydromorphone and naltrindole was replaced by a carboxamido group and the furan ring was opened to the corresponding 4-OH derivatives. These furan ring 'open' derivatives display very high affinity for mu and kappa receptors and much less affinity for delta. The observation that these target compounds have much higher receptor affinity than the corresponding ring 'closed' carboxamides significantly strengthens our underlying pharmacophore hypothesis concerning the bioactive conformation of the carboxamide group.
Wentland
Mark P
MP
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wentmp@rpi.edu
Lou
Rongliang
R
Lu
Qun
Q
Bu
Yigong
Y
Denhardt
Christoph
C
Jin
Jin
J
Ganorkar
Rakesh
R
VanAlstine
Melissa A
MA
Guo
Chengyun
C
Cohen
Dana J
DJ
Bidlack
Jean M
JM
D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000378:metabolism; D018360:Crystallography, X-Ray; D005663:Furans / Q000138:chemical synthesis / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009271:Naltrexone / Q000138:chemical synthesis / Q000378:metabolism; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*
D000701:Analgesics, Opioid; D005663:Furans; D008024:Ligands; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009271:Naltrexone