The identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists: From acid to non-acid.

We disclose herein our preliminary SAR study on the identification of substituted benzothiophene derivatives as PGE(2) subtype 4 receptor antagonists. A potent EP(4) antagonist 6a (K(i)=1.4nM with 10% HSA) was identified. Furthermore, we found that an acidic group was not essential for the EP(4) antagonizing activity in the series and neutral replacements were identified. This opens a new direction for future EP(4) antagonist design.