PAR4 antagonist7 (Compound 20f) is a selective PAR4 antagonist (IC50: 1.72 nM), effective in inhibiting platelet aggregation induced by PAR4 agonists. It exhibits good metabolic stability and has not shown any tendency to cause bleeding in mice.

PAR4 antagonist 7 inhibits the aggregation of washed platelets (WP) induced by the PAR4 agonist peptide (PAR4-AP) (75 μM), with an IC50 of 15.32 nM. It also suppresses the levels of human platelet-rich plasma (PRP) triggered by PAR4-AP (75 μM), attaining an IC50 value of 6.39 nM. Furthermore, PAR4 antagonist 7 inhibits the aggregation of human PRP platelets induced by AYPGKF-NH2 (75 μM) or thrombin (0.1 U/mL) and does not affect platelet aggregation stimulated by SFLLRN-NH2 (5 μM), collagen (10 mg/mL), ADP (10 μM), or U46619 (3 μM). Additionally, it demonstrates excellent metabolic stability in human liver microsomes with a half-life (T1/2) of 249.83 minutes.

PAR4 antagonist 7, administered at doses ranging from 2.5 to 10 mg/kg via oral gavage, did not exhibit any tendencies to cause bleeding in mice, thus demonstrating potential for mitigating bleeding risks.