Minor Structural Modifications Convert the Dual TP/CRTH2 Antagonist Ramatroban into a Highly Selective and Potent CRTH2 Antagonist

摘要

Ramatroban,a thromboxane A_2 receptor (TP) antagonist with clinical efficacy in asthma and allergic rhinitis,was recently shown to also antagonize the prostaglandin D_2 receptor CRTH2.Here we report that minor structural changes to ramatroban result in a compound (13) with complete lack of activity on TP but sub-nanomolar potency toward CRTH2.This is the first selective CRTH2 antagonist described to date,and should prove highly valuable in further elucidating the biological significance of CRTH2.