Understanding the structural requirements of 4-anilidopiperidine analogues for biological activities at mu and delta opioid receptors.
New 4-anilidopiperidine analogues in which the phenethyl group of fentanyl was replaced by several aromatic ring-contained amino acids (or acids) were synthesized to study the biological effect of the substituents on mu and delta opioid receptor interactions. These analogues showed broad (47 nM-76 microM) but selective (up to 17-fold) binding affinities at the mu opioid receptor over the delta opioid receptor, as predicted from the message-address concept.
Lee
Yeon Sun
YS
Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.
Nyberg
Joel
J
Moye
Sharif
S
Agnes
Richard S
RS
Davis
Peg
P
Ma
Shou-wu
SW
Lai
Josephine
J
Porreca
Frank
F
Vardanyan
Ruben
R
Hruby
Victor J
VJ
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D010880:Piperidines / Q000737:chemistry* / Q000493:pharmacokinetics*; D011485:Protein Binding; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
D000700:Analgesics; D008024:Ligands; D010880:Piperidines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu