Identification of the minimum PAR4 inhibitor pharmacophore and optimization of a series of 2-methoxy-6-arylimidazo[2,1-b][1,3,4]thiadiazoles
Graphical abstract
Section snippets
Acknowledgments
We thank the NIH for funding (NS081669 and NS082198.) We also thank William K. Warren, Jr. and the William K. Warren Foundation who funded the William K. Warren, Jr. Chair in Medicine (to C.W.L.).
References and notes (15)
- et al.
J. Thromb. Haemost.
(2016) - et al.
Bioorg. Med. Chem. Lett.
(2014) - et al.
Cell. Commun. Signal.
(2013) - et al.
Mol. Pharm.
(2013) - et al.
J. Med. Chem.
(2016) - et al.
J. Med. Chem.
(2001) - et al.
PLOS One
(2013)
Cited by (7)
Discovery of 7, 4′-dimethoxy-3-hydroxyflavone as a protease-activated receptor 4 antagonist with antithrombotic activity and less bleeding tendency in mice
2022, Biochemical PharmacologyCitation Excerpt :However, the high lipophilicity (LogP > 5) and the instability in plasma may limit its in vivo efficacy and clinical application [45]. In the past decade, a number of small-molecule PAR4 antagonists with new chemical scaffolds have been reported, including indole [45–47] and imidazothiadiazole [48,49] analogues, but only few have been evaluated for antithrombotic effects in whole-blood systems or in animal models. Given that the only one licensed PAR1 antagonist, vorapaxar, is a synthetic derivative of the alkaloid himbacine [50], it is expectable that natural products could be a useful source for the discovery of novel PAR4 antagonists.
Protease activated receptor 4 (PAR4) antagonists: Research progress on small molecules in the field of antiplatelet agents
2021, European Journal of Medicinal ChemistryCitation Excerpt :And other compounds are in preclinical stage. In general, small-molecule PAR4 antagonists that have been reported include indazole [44–50], indole [51–58], imidazole [2,1-b][1,3,4]thiadiazole (IDT) [39,59–73], quinoline and quinoxaline [74–78] analogues. No PAR4 antagonist has been approved for marketing, which is a pity but also an opportunity to develop a ‘first-in-class’ PAR4 antagonist.
Discovery of Potent and Selective Quinoxaline-Based Protease-Activated Receptor 4 (PAR4) Antagonists for the Prevention of Arterial Thrombosis
2024, Journal of Medicinal ChemistryTherapeutic charisma of imidazo [2,1-b] [1,3,4]-thiadiazole analogues: a patent review
2023, Pharmaceutical Patent AnalystInhibitors of protease-activated receptor 4 (PAR4): a review of recent patents (2013–2021)
2022, Expert Opinion on Therapeutic Patents
- †
These authors contributed equally.