Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. Part 6: Opioid receptor binding properties of cyclic variants of 8-carboxamidocyclazocine.
A series of 7,8- and 8,9-fused pyrimidinone, aminopyrimidine and pyridone derivatives of 8-carboxamidocyclazocine (8-CAC) have been prepared and evaluated in opioid receptor binding assays. Targets were designed to corroborate a pharmacophore hypothesis regarding the bioactive conformation of the carboxamide of 8-CAC. In addition to the results from this study strongly supporting this pharmacophore hypothesis, a number of novel compounds with high affinity to opioid receptors have been identified.
Wentland
Mark P
MP
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wentmp@rpi.edu
Sun
Xufeng
X
Cohen
Dana J
DJ
Bidlack
Jean M
JM
D000818:Animals; D001392:Azocines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008968:Molecular Conformation; D009292:Narcotic Antagonists; D011957:Receptors, Opioid / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C459385:8-carboxamidocyclazocine; D001392:Azocines; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D003496:Cyclazocine