Novel tricyclic antagonists of the prostaglandin D2 receptor DP2 with efficacy in a murine model of allergic rhinitis.

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.

• Authors: Brian A Stearns, Christopher Baccei, Gretchen Bain, Alex Broadhead, Ryan C Clark, Heather Coate, Jilly F Evans, Patrick Fagan, John H Hutchinson, Christopher King, Catherine Lee, Daniel S Lorrain, Peppi Prasit, Pat Prodanovich, Angelina Santini, Jill M Scott, Nicholas S Stock, Yen P Truong
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 16 Pg. 4647-51 (Aug 15 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19608418 (Publication Type: Journal Article)

Chemical References

• Anti-Allergic Agents
• Anti-Inflammatory Agents
• Heterocyclic Compounds, 3-Ring
• Receptors, Immunologic
• Receptors, Prostaglandin
• Cytochrome P-450 Enzyme System
• prostaglandin D2 receptor

Topics

• Animals
• Anti-Allergic Agents (chemical synthesis, chemistry, pharmacology)
• Anti-Inflammatory Agents (chemical synthesis, chemistry, pharmacology)
• Cytochrome P-450 Enzyme System (metabolism)
• Disease Models, Animal
• Female
• Heterocyclic Compounds, 3-Ring (chemical synthesis, chemistry, pharmacology)
• Humans
• Mice
• Receptors, Immunologic (antagonists & inhibitors, metabolism)
• Receptors, Prostaglandin (antagonists & inhibitors, metabolism)
• Rhinitis, Allergic, Perennial (drug therapy)