Identification of an indole series of prostaglandin D2 receptor antagonists

Abstract A novel indole series of PGD 2 receptor (DP receptor) antagonists is presented. Optimization of this series led to the identification of potent and selective DP receptor antagonists. In particular, antagonists 35 and 36 were identified with K i values of 2.6 and 1.8 nM, respectively. These two antagonists are also potent in a DP functional assay where they inhibit the PGD 2 induced cAMP production in platelet rich plasma with IC 50 values of 7.9 and 8.6 nM, respectively. The structure–activity relationships of this indole series of DP receptor antagonists will also be discussed.