Synthesis and biological evaluation of C-12 triazole and oxadiazole analogs of salvinorin A.
Bioorg Med Chem Lett
; 19(5): 1301-4, 2009 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-19211245
ABSTRACT
Salvinorin A (1), the main active ingredient of Salvia divinorum, is a potent and selective kappa-opioid receptor (KOPR) agonist. A series of C-12 triazole analogs and the oxadiazole (4) analog of 1 are synthesized and screened for binding affinity at kappa, mu (MOPR), or delta (DOPR). Surprisingly, all triazole analogs have shown negligible binding affinity at opioid receptors and the oxadiazole 4, a reported MOPR and KOPR antagonist, exhibits very low affinities to opioid receptors and no antagonism in our binding assays. These results suggest that electronic factors that may affect either the electron density of hydrogen bond acceptor at C-12 or hydrophobic interactions between C-12 moiety and KOPR are critical to C-12 analog's affinity for KOPR.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oxadiazoles
/
Triazoles
/
Carbono
/
Diterpenos de Tipo Clerodano
Límite:
Animals
/
Humans
Idioma:
En
Año:
2009
Tipo del documento:
Article