14-amino, 14-alkylamino, and 14-acylamino analogs of oxymorphindole. Differential effects on opioid receptor binding and functional profiles.
The 14-amino analogue of oxymorphindole (OMI) was synthesized and found to possess delta-opioid binding affinity and selectivity similar to OMI. Substitution of the amino group with alkyl, arylalkyl, and acyl groups had relatively little effect on delta-affinity but delta-selectivity was reduced. In functional assays the 14-phenylacetylamino derivative 6d was a selective delta-agonist whereas the phenethylamino analogue 5d was a mu-agonist and low efficacy delta partial agonist that warrants further investigation as an analgesic with low tolerance and dependence.
Grundt
Peter
P
Department of Pharmacy and Pharmacology, University of Bath, UK.
Jales
Andrew R
AR
Traynor
John R
JR
Lewis
John W
JW
Husbands
Stephen M
SM
D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D009025:Morpholines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C070418:oxymorphindole