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Updated: May 24, 2026

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Published on: May 24, 2024
Discovery of nor-seco himbacine analogs as thrombin receptor antagonists
Mariappan V Chelliah1, Samuel Chackalamannil, Yan Xia
1Central Nervous System and Cardiovascular Chemical Research, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. Joseph.Warmus@Pfizer.com
Abstract:
Discovery of a novel nor-seco himbacine analog as potent thrombin receptor (PAR-1) antagonist is described. Despite low plasma level, these new analogs showed excellent ex vivo efficacy in the monkey platelet aggregation assay. A potent hydroxy metabolite generated in vivo was identified as the agent responsible for the ex vivo efficacy. Following this discovery, the metabolite series was optimized to obtain analogs that showed very good ex vivo efficacy along with excellent pharmacokinetic profile in c. monkey.
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