Abstract
A new class of potent NK3R antagonists based on the N',2-diphenylquinoline-4-carbohydrazide core is described. In an ex vivo assay in gerbil, the lead compound 2g occupies receptors within the CNS following oral dosing (Occ(90) 30 mg/kg po; plasma Occ(90) 0.95 microM) and has good selectivity and promising PK properties.
MeSH terms
-
Administration, Oral
-
Animals
-
CHO Cells
-
Cricetinae
-
Dose-Response Relationship, Drug
-
Hydrazines / chemistry*
-
Hydrazines / pharmacology*
-
Neurotransmitter Agents / chemistry*
-
Neurotransmitter Agents / pharmacology*
-
Quinolines / chemistry*
-
Quinolines / pharmacology*
-
Receptors, Neurokinin-3 / antagonists & inhibitors*
-
Structure-Activity Relationship
-
Tumor Cells, Cultured
Substances
-
Hydrazines
-
N-((methoxycarbonyl)(phenyl)amino)-3-methoxy-2-phenylquinoline-4-carboxamide
-
Neurotransmitter Agents
-
Quinolines
-
Receptors, Neurokinin-3
-
carbohydrazide