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Chen P , Zhang D , Li M , Wu Q , Lam YPY , Guo Y , Chen C , Bai N , Malhotra S , Li W , O'Connor PB , Fu H
Discovery of novel, potent, isosteviol-based antithrombotic agents
Eur J Med Chem. 2019 Dec 1;183 :111722
PMID: 31563807 URL: https://www.ncbi.nlm.nih.gov/pubmed/31563807
AbstractThrombosis is a pathological coagulation process and can lead to many serious thrombotic diseases. Here, we report a novel potent antithrombotic compound (6k) based on isosteviol with anticoagulant and antiplatelet activities. 6k selectively inhibited FXa (Ki=0.015muM) against a panel of serine proteases and showed excellent anticoagulant activity (significant prolongation of ex vivo PT and aPTT over the vehicle, p<0.01). 6k also significantly inhibited ADP-induced platelet aggregation in rats relative to the vehicle (p<0.01). Furthermore, 6k exhibited potent ex vivo and in vivo antithrombotic activity in rats relative to the vehicle (p<0.01 and p<0.0001, respectively). Novel structure 6k, with potent antithrombotic activity, is expected to lead a promising approach for the development of antithrombotic agents.
Notes1768-3254 Chen, Peng Zhang, Dianwen Li, Meng Wu, Qiong Lam, Yuko P Y Guo, Yan Chen, Chen Bai, Nan Malhotra, Shipra Li, Wei O'Connor, Peter B Fu, Hongzheng Journal Article France Eur J Med Chem. 2019 Dec 1;183:111722. doi: 10.1016/j.ejmech.2019.111722. Epub 2019 Sep 19.