Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. 5. Opioid receptor binding properties of N-((4'-phenyl)-phenethyl) analogues of 8-CAC.
A series of aryl-containing N-monosubstituted analogues of the lead compound 8-[N-((4'-phenyl)-phenethyl)]-carboxamidocyclazocine were synthesized and evaluated to probe a putative hydrophobic binding pocket of opioid receptors. Very high binding affinity to the mu opioid receptor was achieved though the N-(2-(4'-methoxybiphenyl-4-yl)ethyl) analogue of 8-CAC. High binding affinity to mu and very high binding affinity to kappa opioid receptors was observed for the N-(3-bromophenethyl) analogue of 8-CAC. High binding affinity to all three opioid receptors were observed for the N-(2-naphthylethyl) analogue of 8-CAC.
VanAlstine
Melissa A
MA
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Wentland
Mark P
MP
Cohen
Dana J
DJ
Bidlack
Jean M
JM
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship
C459385:8-carboxamidocyclazocine; D011957:Receptors, Opioid; D003496:Cyclazocine