Synthesis of a Novel Series of Amino Acid Prodrugs Based on Thienopyridine Scaffolds and Evaluation of Their Antiplatelet Activity

Figure 1. The representative chemical structures of drugs of ADP receptor antagonist.

Figure 2. Simplified biosynthetic mechanism of the active units of thienopyridines and prodrug design.

Scheme 1. Synthetic route of compounds 5a–5p. Reagents and conditions: (i) K2CO3, CH3CN, r.t. overnight (60–65% yield); (ii) N-Boc-l-amino acid, EDCI, DMAP, DCM, 0 °C-r.t., 4 h (71–86% yield); (iii) hydrochloric ethyl acetate, r.t., 5 h (84–93% yield).

Figure 3. Inhibition ratios of all compounds at doses of 3 mg/kg and 1 mg/kg.

Figure 4. The platelet aggregation of 5c, 5k, clopidogrel and prasugrel at different doses. ** p < 0.01 vs. vehicle. Data are the mean ± SD, n = 5).

Figure 5. The bleeding time of 5c and 5k at different doses. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. vehicle. Data are the mean ± SD, n = 5).