4-[(8-Alkyl-8-azabicyclo[3.2.1]octyl-3-yl)-3-arylanilino]-N,N-diethylbenzamides: high affinity, selective ligands for the delta opioid receptor illustrate factors important to antagonist activity.
The tropane derived compounds, 4-[(8-alkyl-8-azabicyclo[3.2.1]octyl-3-yl)-3-arylanilino]-N,N-d iethylbenzamides (5a-d), were synthesized and found to have high affinity and selectivity for the delta receptor. Compounds 5a-d are structurally similar to the full agonist (-)-RTI-5989-54 (3); yet, efficacy studies for compounds in this series (5a-d) reveal greatly diminished agonist activity as well as antagonism not found in piperidine-based compounds like 3.
Thomas
J B
JB
Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, NC 27709, USA.
Atkinson
R N
RN
Rothman
R B
RB
Burgess
J P
JP
Mascarella
S W
SW
Dersch
C M
CM
Xu
H
H
Carroll
F I
FI
D001549:Benzamides / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001549:Benzamides; D008024:Ligands; D017465:Receptors, Opioid, delta