Synthesis and pharmacology of 8-amino-3-(tetrahydro-2-furanyl)methyl benzomorphan.
- Author:
Qun ZHOU
1
;
Wen-hu DUAN
;
Dana J COHEN
;
Jean M BIDLACK
;
Mark P WENTLAND
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Benzomorphans; chemical synthesis; chemistry; pharmacology; Brain; metabolism; Furans; chemical synthesis; chemistry; pharmacology; Guinea Pigs; Molecular Structure; Narcotic Antagonists; chemical synthesis; chemistry; pharmacology; Radioligand Assay; Receptors, Opioid; metabolism; Receptors, Opioid, delta; metabolism; Receptors, Opioid, kappa; metabolism; Receptors, Opioid, mu; metabolism; Structure-Activity Relationship
- From: Acta Pharmaceutica Sinica 2003;38(10):748-753
- CountryChina
- Language:English
-
Abstract:
AIMTo design and synthesize new chiral 8-(substituted) amino-analogues of 3-[(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the structure-activity relationship (SAR) for 8-aminobenzomorphan.
METHODSTarget compounds were synthesized from the 8-triflate of the optically active 3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphans using Pd-catalyzed aminations. Opioid receptor binding experiments were performed to evaluate their biological activities.
RESULTSBoth 8-amino and 8-phenylamino analogues showed lower binding affinity for mu, delta and kappa receptors than corresponding 8-hydroxy-3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphan in vitro.
CONCLUSIONThe relative poor binding affinity of the target compounds did not warrant conducting the in vivo studies to determine if they have the profile(kappa agonist/mu antagonist) that will be potentially useful in the treatment of drug addiction. Further study is in progress.
