Abstract
On the basis of the structural features of the Dmt-Tic pharmacophore, a new motif leading to a fairly potent mu-opioid antagonist is described. This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constraint compatible with the mu-opioid receptor. The stereoselective synthesis of four stereoisomers is performed starting from homochiral 2',6'-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Benzazepines / chemical synthesis*
-
Benzazepines / chemistry
-
Benzazepines / pharmacology
-
Electric Stimulation
-
Guinea Pigs
-
Ileum / drug effects
-
Ileum / physiology
-
In Vitro Techniques
-
Muscle Contraction
-
Muscle, Smooth / drug effects
-
Muscle, Smooth / physiology
-
Propane / analogs & derivatives
-
Propane / chemical synthesis
-
Propane / chemistry
-
Propane / pharmacology
-
Radioligand Assay
-
Receptors, Opioid, mu / antagonists & inhibitors*
-
Receptors, Opioid, mu / physiology
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
Benzazepines
-
Receptors, Opioid, mu
-
Propane