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Updated: Jul 11, 2026

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
Published on: May 24, 2024
Heterotricyclic himbacine analogs as potent, orally active thrombin receptor (protease activated receptor-1)
Mariappan V Chelliah1, Samuel Chackalamannil, Yan Xia
1Central Nervous System and Cardiovascular Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. mariappan.chelliah@spcorp.com
Abstract:
Pursuing our earlier efforts in the himbacine-based thrombin receptor antagonist area, we have synthesized a series of compounds that incorporate heteroatoms in the C-ring of the tricyclic motif. This effort has resulted in the identification of several potent heterocyclic analogs with excellent affinity for the thrombin receptor. Several of these compounds demonstrated robust inhibition of platelet aggregation in an ex vivo model in cynomolgus monkeys following oral administration. A detailed profile of 28b, a benchmark compound in this series, with a Ki of 4.3 nM, is presented.
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