Synthesis and opioid receptor binding properties of a highly potent 4-hydroxy analogue of naltrexone.
Very high affinity for opioid receptors (e.g., K(i)=0.052nM for mu) has been observed in the rationally designed naltrexone analogue 5. SAR and physical data supports the hypothesis that the 4-OH group of 5 stabilizes the 3-carboxamido group in the putative bioactive conformation.
Wentland
Mark P
MP
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wentmp@rpi.edu <wentmp@rpi.edu>
Lu
Qun
Q
Lou
Rongliang
R
Bu
Yigong
Y
Knapp
Brian I
BI
Bidlack
Jean M
JM
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism*
D011957:Receptors, Opioid; D009271:Naltrexone