8-Aminocyclazocine analogues: synthesis and structure-activity relationships.
Opioid binding affinities were assessed for a series of cyclazocine analogues where the prototypic 8-OH substituent of cyclazocine was replaced by amino and substituted-amino groups. For mu and kappa opioid receptors, secondary amine derivatives having the (2R,6R,11R)-configuration had the highest affinity. Most targets were efficiently synthesized from the triflate of cyclazocine or its enantiomers using Pd-catalyzed amination procedures.
Wentland
M P
MP
Departmnent of Chemistry, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Xu
G
G
Cioffi
C L
CL
Ye
Y
Y
Duan
W
W
Cohen
D J
DJ
Colasurdo
A M
AM
Bidlack
J M
JM
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000737:chemistry; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D006168:Guinea Pigs; D015394:Molecular Structure; D009271:Naltrexone / Q000031:analogs & derivatives / Q000378:metabolism; D009292:Narcotic Antagonists; D011759:Pyrrolidines / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C023462:8-aminocyclazocine; D000700:Analgesics; D044482:Benzeneacetamides; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; C055382:naltrindole; C045444:U 69593; D003496:Cyclazocine