title: Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2.
abstract: Prostaglandin D2 (PGD2) acting at the CRTH2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells) has been linked with a variety of allergic and other inflammatory diseases. We describe a family of indole-1-sulfonyl-3-acetic acids that are potent and selective CRTH2 antagonists that possess good oral bioavailability. The compounds may serve as novel starting points for the development of treatments of inflammatory disease such as asthma, allergic rhinitis, and atopic dermatitis.
authors.affiliation: Oxagen Ltd., 91 Milton Park, Abingdon, Oxfordshire, OX14 4RY, UK. r.armer@oxagen.co.uk
authors.forename: Richard E
authors.initials: RE
authors.lastname: Armer
authors.forename: Mark R
authors.initials: MR
authors.lastname: Ashton
authors.forename: Edward A
authors.initials: EA
authors.lastname: Boyd
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Brennan
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Brookfield
authors.forename: Lucien
authors.initials: L
authors.lastname: Gazi
authors.forename: Shân L
authors.initials: SL
authors.lastname: Gyles
authors.forename: Philip A
authors.initials: PA
authors.lastname: Hay
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hunter
authors.forename: David
authors.initials: D
authors.lastname: Middlemiss
authors.forename: Mark
authors.initials: M
authors.lastname: Whittaker
authors.forename: Luzheng
authors.initials: L
authors.lastname: Xue
authors.forename: Roy
authors.initials: R
authors.lastname: Pettipher
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007210:Indoleacetic Acids / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology; D051381:Rats; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013450:Sulfones; C030737:indoleacetic acid; D015230:Prostaglandin D2; D002118:Calcium; C036293:prostaglandin D2 receptor