Table 1.
Binding affinity and functional antagonism on hCRTH2 for preliminary aryl amides and structure–activity relationship (SAR) on the amide linker (values were obtained from [73]).
| Compd. | hCRTH2 a (Ki) | cAMP b (IC50) | EOS c,d (IC50) |
|---|---|---|---|
| 27 | 340 nM | 2500 nM | |
| 28 | 7.4 nM | 12 nM | 4.8 nM |
| 29 | 3.0 nM | 6.2 nM | 6.0 nM |
| 30 | 2.0 nM | 2.0 nM | 4.4 nM |
| 31 | 1.8 nM | 4.0 nM | |
| 32 | 1.7 nM | 4.0 nM | 1.4 nM |
| 33 | 4.3 nM | 8.0 nM | 2.4 nM |
| 34 | 141 nM | ||
| 35 | 70 nM | ||
| 36 | 22 nM | ||
| 37 | 126 nM | ||
| 38 | 19 nM | ||
| 39 | 408 nM | ||
| 40 | 4.0 nM | 3.0 nM | 0.96 nM |
| 41 | 39 nM | 30 nM |
a Radioligand competition binding assay using membrane proteins from HEK293 (EBNA) cells stably expressing the receptor CRTH2 in a 10 mM solution of HEPES/KOH (all values are mean of two or more experiments). b Functional assay: the intracellular concentration of cAMP was determined using the 125I-cAMP scintillation proximity assay. The assay was performed in Hank’s balanced salt solution 25 mM HEPES containing 5000 nM Forskolin (Ki is an average of at least two independent titrations). c IC50s are an average of at least two independent titrations. d Whole blood eosinophil shape change assay.