title: A new structural motif for mu-opioid antagonists.
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.
authors.affiliation: Eenheid Organische Chemie, Vrije Universiteit Brussel, 2, Pleinlaan, B-1050 Brussels, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van den Eynde
authors.forename: Georges
authors.initials: G
authors.lastname: Laus
authors.forename: Peter W
authors.initials: PW
authors.lastname: Schiller
authors.forename: Piotr
authors.initials: P
authors.lastname: Kosson
authors.forename: Nga N
authors.initials: NN
authors.lastname: Chung
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
authors.forename: Dirk
authors.initials: D
authors.lastname: Tourwé
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011407:Propane / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001552:Benzazepines; D017450:Receptors, Opioid, mu; D011407:Propane