The consistent increases in platelet reactivity observed in response to a range of agonists provides a plausible underlying mechanism to explain the reversible increased rates of MI observed in abacavir-treated patients.

Between-group differences in platelet responses to all agonists suggest multiple underlying defects in platelet function in HIV infection. Further research is required to determine the contribution of antiretroviral therapy and relationships between platelet function and the increased cardiovascular disease observed in HIV-infected populations.

To cite this article: Peace AJ, Tedesco AF, Foley DP, Dicker P, Berndt MC, Kenny D. Dual antiplatelet therapy unmasks distinct platelet reactivity in patients with coronary artery disease.

The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkylation. Subsequent palladium-catalyzed intramolecular direct arylation efficiently builds the central seven-membered ring. The target was prepared in 12 linear steps with five isolations in an overall yield of 8%.

Patients with active IA demonstrate enhanced platelet reactivity, unique to the ADP pathway. This potential pro-thrombotic bias may contribute to their increased cardiovascular risk.