Non-basic azolotriazinone MCHR1 antagonists for the treatment of obesity: An empirical brain-exposures-driven candidate selection for in vivo efficacy studies.
Bioorg Med Chem Lett
; 25(20): 4412-8, 2015 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-26386604
ABSTRACT
Non-basic azolotriazinones were explored using an empirical free brain exposures-driven approach to identify potent MCHR1 antagonists for evaluation in in vivo efficacy studies. An optimized lead from this series, 1j (rMCHR1 Ki=1.8 nM), demonstrated a 6.9% reduction in weight gain relative to vehicle in a rat model at 30 mg/kg after 4 days of once-daily oral treatment as a glycine prodrug. Despite a promising efficacy profile, an assessment of the biliary toxicity risk of this compound rendered this compound non-progressible.
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1
Banco de datos:
MEDLINE
Asunto principal:
Triazinas
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Encéfalo
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Receptores de Somatostatina
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Obesidad
Límite:
Animals
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Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article