Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2.
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.
Armer
Richard E
RE
Oxagen Ltd., 91 Milton Park, Abingdon, Oxfordshire, OX14 4RY, UK. r.armer@oxagen.co.uk
Ashton
Mark R
MR
Boyd
Edward A
EA
Brennan
Chris J
CJ
Brookfield
Frederick A
FA
Gazi
Lucien
L
Gyles
Shân L
SL
Hay
Philip A
PA
Hunter
Michael G
MG
Middlemiss
David
D
Whittaker
Mark
M
Xue
Luzheng
L
Pettipher
Roy
R
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
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