Dockendorff, Chris; Aisiku, Omozuanvbo; VerPlank, Lynn; Dilks, James R.; Smith, Daniel A.; Gunnink, Susanna F.; Dowal, Louisa; Negri, Joseph; Palmer, Michelle; MacPherson, Lawrence; Schreiber, Stuart L.; Flaumenhaft, Robert published the artcile< Discovery of 1,3-Diaminobenzenes as Selective Inhibitors of Platelet Activation at the PAR1 Receptor>, Category: chlorides-buliding-blocks, the main research area is preparation of antithrombotic agent platelet activation inhibition PAR1.
A high-throughput screen of the NIH-MLSMR compound collection, along with a series of secondary assays to identify potential targets of hit compounds, previously identified a 1,3-diaminobenzene scaffold that targets protease-activated receptor 1 (PAR1). We now report addnl. structure-activity relationship (SAR) studies that delineate the requirements for activity at PAR1 and identify plasma-stable analogs with nanomolar inhibition of PAR1-mediated platelet activation. Compound 4 was declared as a probe (ML161) with the NIH Mol. Libraries Program. This compound inhibited platelet aggregation induced by a PAR1 peptide agonist or by thrombin but not by several other platelet agonists. Initial studies suggest that ML161 is an allosteric inhibitor of PAR1. These findings may be important for the discovery of antithrombotics with an improved safety profile.
ACS Medicinal Chemistry Letters published new progress about Anticoagulants. 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Category: chlorides-buliding-blocks.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics