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Updated: Apr 28, 2026

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Himbacine-derived thrombin receptor antagonists: c7-spirocyclic analogues of vorapaxar
Mariappan V Chelliah1, Keith Eagen1, Zhuyan Guo1
1Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033-1300, United States.
Abstract:
We have synthesized several C7-spirocyclic analogues of vorapaxar and evaluated their in vitro activities against PAR-1 receptor. Some of these analogues showed activities and rat plasma levels comparable to vorapaxar. Compound 5c from this series showed excellent PAR-1 activity (K i = 5.1 nM). We also present a model of these spirocyclic compounds docked to the PAR-1 receptor based on the X-ray crystal structure of vorapaxar bound to PAR-1 receptor. This model explains some of the structure-activity relationships in this series.
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