Abstract
The synthesis and biological evaluation of novel 3-amino indazole melanin concentrating hormone receptor-1 antagonists are reported, several of which demonstrated functional activity of less than 100nM. Compounds 19 and 28, two of the more potent compounds identified in this study, were characterized by high exposure in the brain and demonstrated robust efficacy when dosed in diet-induced obese mice.
MeSH terms
-
Administration, Oral
-
Animals
-
Anti-Obesity Agents / administration & dosage
-
Anti-Obesity Agents / chemical synthesis*
-
Anti-Obesity Agents / pharmacology*
-
Humans
-
Indazoles / administration & dosage
-
Indazoles / chemical synthesis*
-
Indazoles / pharmacology*
-
Mice
-
Piperidines / chemistry
-
Receptors, Somatostatin / antagonists & inhibitors*
-
Tissue Distribution
Substances
-
Anti-Obesity Agents
-
Indazoles
-
MCHR1 protein, human
-
Piperidines
-
Receptors, Somatostatin
-
piperidine