Synthesis and evaluation of novel fluorinated sulotroban-related sulfonamide derivatives as thromboxane A2 receptor antagonists

Article abstract of DOI:10.1016/0223-5234(96)88250-X

A series of sulotroban-related arylsulfonamide derivatives possessing a fluorinated phenoxyacetic acid moiety was synthesized and tested for TXA₂ antagonizing ability on U-46619-induced platelet aggregation of rabbit platelet-rich plasma. Introduction of one or more fluorine atoms to the phenoxyacetic acid moiety increased this activity. The most potent compound among these compounds was 10c, which was 40-fold more potent (IC₅₀ 3.4 x 10-⁷ M) than sulotroban. 10c exhibited high activity (ID₅₀ 0.14 mg/kg) against a D-46619-induced acute thrombocytopenia model in mice when orally administrated. These findings and those of radioligand binding assays with various ligands showed 10c to be a potent and selective systemic TXA₂ receptor antagonist.