Abstract
The synthesis of a series of tricyclic antagonists for the prostaglandin D(2) receptor DP2 (CRTH2) is disclosed. The activities of the compounds were evaluated in a human DP2 binding assay and a human whole blood eosinophil shape change assay. Potential metabolic liabilities of the compounds were addressed through in vitro CYP studies. The lead compound was demonstrated to have efficacy in a mouse model of allergic rhinitis following oral dosing.
MeSH terms
-
Animals
-
Anti-Allergic Agents / chemical synthesis
-
Anti-Allergic Agents / chemistry*
-
Anti-Allergic Agents / pharmacology
-
Anti-Inflammatory Agents / chemical synthesis
-
Anti-Inflammatory Agents / chemistry*
-
Anti-Inflammatory Agents / pharmacology
-
Cytochrome P-450 Enzyme System / metabolism
-
Disease Models, Animal
-
Female
-
Heterocyclic Compounds, 3-Ring / chemical synthesis
-
Heterocyclic Compounds, 3-Ring / chemistry*
-
Heterocyclic Compounds, 3-Ring / pharmacology
-
Humans
-
Mice
-
Receptors, Immunologic / antagonists & inhibitors*
-
Receptors, Immunologic / metabolism
-
Receptors, Prostaglandin / antagonists & inhibitors*
-
Receptors, Prostaglandin / metabolism
-
Rhinitis, Allergic, Perennial / drug therapy*
Substances
-
Anti-Allergic Agents
-
Anti-Inflammatory Agents
-
Heterocyclic Compounds, 3-Ring
-
Receptors, Immunologic
-
Receptors, Prostaglandin
-
Cytochrome P-450 Enzyme System
-
prostaglandin D2 receptor