Abstract
The discovery and structure-activity relationship of 1,2-diarylimidazole piperazine carboxamides bearing polar side chains as potent and selective cholecystokinin 1 receptor (CCK1R) agonists are described. Optimization of this series resulted in the discovery of isopropyl carboxamide 40, a CCK1R agonist with sub-nanomolar functional and binding activity as well as excellent potency in a mouse overnight food intake reduction assay.
MeSH terms
-
Animals
-
Anti-Obesity Agents / chemical synthesis
-
Anti-Obesity Agents / chemistry
-
Anti-Obesity Agents / pharmacology*
-
Benzodiazepines / chemical synthesis
-
Benzodiazepines / chemistry
-
Benzodiazepines / pharmacology*
-
Chemokines, CC
-
Humans
-
Indoles / chemical synthesis
-
Indoles / chemistry
-
Indoles / pharmacology*
-
Methylamines / chemical synthesis
-
Methylamines / chemistry
-
Methylamines / pharmacology
-
Mice
-
Obesity / drug therapy*
-
Piperazine
-
Piperazines / chemistry
-
Receptor, Cholecystokinin A / agonists*
-
Receptors, Cholecystokinin / agonists
-
Receptors, Cholecystokinin / chemistry
-
Thiazoles / chemical synthesis
-
Thiazoles / chemistry
-
Thiazoles / pharmacology*
Substances
-
Anti-Obesity Agents
-
Ccl28 protein, mouse
-
Chemokines, CC
-
GI 181771X
-
Indoles
-
Methylamines
-
Piperazines
-
Receptor, Cholecystokinin A
-
Receptors, Cholecystokinin
-
SR 146131
-
Thiazoles
-
Benzodiazepines
-
Piperazine