| Literature DB >> 16161991 |
Samuel Chackalamannil1, Yan Xia, William J Greenlee, Martin Clasby, Darìo Doller, Hsingan Tsai, Theodros Asberom, Michael Czarniecki, Ho-Sam Ahn, George Boykow, Carolyn Foster, Jacqueline Agans-Fantuzzi, Matthew Bryant, Janice Lau, Madhu Chintala.
Abstract
Structurally novel thrombin receptor (protease activated receptor 1, PAR-1) antagonists based on the natural product himbacine are described. The prototypical PAR-1 antagonist 55 showed a Ki of 2.7 nM in the binding assay, making it the most potent PAR-1 antagonist reported. 55 was highly active in several functional assays, showed excellent oral bioavailability in rat and monkey models, and showed complete inhibition of agonist-induced ex vivo platelet aggregation in cynomolgus monkeys after oral administration.Entities:
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Year: 2005 PMID： 16161991 DOI： 10.1021/jm0502236
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446