{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dunker C"],"funding":["Deutsche Forschungsgemeinschaft (DFG)","Deutsche Forschungsgemeinschaft"],"pagination":["1340"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9696832"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(11)"],"pubmed_abstract":["New antithrombotic drugs are needed to combat thrombosis, a dangerous pathology that causes myocardial infarction and ischemic stroke. In this respect, thrombin (FIIa) represents an important drug target. We herein report the synthesis and biological activity of a series of 1<i>H</i>-pyrazol-5-amine-based thrombin inhibitors with a serine-trapping mechanism of action. Among synthesized compounds, flexible acylated 1<i>H</i>-pyrazol-5-amines <b>24e</b>, <b>34a</b>, and <b>34b</b> were identified as potent 16-80 nM thrombin inhibitors, which showed practically no off-targeting effect against other physiologically relevant serine proteases. To prove that synthesized compounds are covalent thrombin inhibitors, the most potent derivative <b>24e</b> (FIIa IC<sub>50</sub> = 16 nM) was studied in "],"journal":["Pharmaceuticals (Basel, Switzerland)"],"pubmed_title":["Pyrazole-Based Thrombin Inhibitors with a Serine-Trapping Mechanism of Action: Synthesis and Biological Activity."],"pmcid":["PMC9696832"],"funding_grant_id":["KA 5558/1-1","DVK: KA 5558/1-1"],"pubmed_authors":["Daniliuc CG","Imberg L","Siutkina AI","Karst U","Erbacher C","Kalinin DV","Dunker C"],"additional_accession":[]},"is_claimable":false,"name":"Pyrazole-Based Thrombin Inhibitors with a Serine-Trapping Mechanism of Action: Synthesis and Biological Activity.","description":"New antithrombotic drugs are needed to combat thrombosis, a dangerous pathology that causes myocardial infarction and ischemic stroke. In this respect, thrombin (FIIa) represents an important drug target. We herein report the synthesis and biological activity of a series of 1<i>H</i>-pyrazol-5-amine-based thrombin inhibitors with a serine-trapping mechanism of action. Among synthesized compounds, flexible acylated 1<i>H</i>-pyrazol-5-amines <b>24e</b>, <b>34a</b>, and <b>34b</b> were identified as potent 16-80 nM thrombin inhibitors, which showed practically no off-targeting effect against other physiologically relevant serine proteases. To prove that synthesized compounds are covalent thrombin inhibitors, the most potent derivative <b>24e</b> (FIIa IC<sub>50</sub> = 16 nM) was studied in ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2026-05-08T03:08:51.295Z","creation":"2024-11-15T15:39:15.624Z"},"accession":"S-EPMC9696832","cross_references":{"pubmed":["36355511"],"doi":["10.3390/ph15111340"]}}