Discovery and optimization of a biphenylacetic acid series of prostaglandin D2 receptor DP2 antagonists with efficacy in a murine model of allergic rhinitis

Autor:	Daniel S. Lorrain, Jill Melissa Scott, Angelina M. Santini, Patrick Fagan, Brian Andrew Stearns, Christopher D. King, Catherine Lee, Christopher Baccei, Hutchinson John H, Pat Prodanovich, Jilly F. Evans, Peppi Prasit, Alex R. Broadhead, Gretchen Bain
Rok vydání:	2010
Předmět:	Rhinitis Allergic Perennial Clinical Biochemistry Receptors Prostaglandin Pharmaceutical Science Prostaglandin Biological Availability Pharmacology Biochemistry chemistry.chemical_compound Mice Dogs Pharmacokinetics Drug Discovery medicine Potency Animals Receptors Immunologic Receptor Molecular Biology Whole blood Prostaglandin D2 receptor Phenylacetates Chemistry Ligand binding assay Organic Chemistry Eosinophil Rats Disease Models Animal medicine.anatomical_structure Immunology Molecular Medicine
Zdroj:	Bioorganicmedicinal chemistry letters. 21(21)
ISSN:	1464-3405
Popis:	Biphenylacetic acid (5) was identified through a library screen as an inhibitor of the prostaglandin D(2) receptor DP2 (CRTH2). Optimization for potency and pharmacokinetic properties led to a series of selective CRTH2 antagonists. Compounds demonstrated potency in a human DP2 binding assay and a human whole blood eosinophil shape change assay, as well as good oral bioavailability in rat and dog, and efficacy in a mouse model of allergic rhinitis following oral dosing.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ff8ab52068f800b3a676abebe5fa4b6 https://pubmed.ncbi.nlm.nih.gov/21958540 Full Text from ScienceDirect