The involvement of prostaglandin D2 (PGD2) in inflammatory diseases like allergy and asthma is well established, and blocking the effect of this mediator represents and interesting therapeutic approach for the treatment of such diseases. PGD2 is now known to act through two seven-transmembrane (7TM) receptors, DP1 (previously DP) and CRTH2 (DP2), which are also activated by several endogenous metabolites from the arachidonic acid cascade, making the regulatory system highly complex. There has recently been a considerable effort aimed at developing antagonists of the PGD2 receptors for treatment of inflammatory conditions like asthma and rhinitis, and especially CRTH2 has received much attention since its identification as the second high affinity PGD2 receptor in 2001. A number of potent and selective antagonists are now available for both receptors. This review will briefly discuss the biological background and validation of DP1 and CRTH2 as targets for antiinflammatory drugs, and then highlight developments in medicinal chemistry which have appeared in journals and patent applications in the last few years, and which have brought us closer to therapeutic applications of PGD2 receptor antagonists in various indications.
Keywords: Prostaglandin D2, DP1, DP2, CRTH2, inflammation, asthma, allergy, drug discovery.