The potency and selectivity of a previous series of low molecular weight thrombin inhibitors were improved through modifications of the P1 and P3 residues. Introduction of diphenyl substituted ...sulfonamides in the P3 moiety led to highly efficacious compounds. By correctly selecting the combination of P1 and P3 residues, high levels of potency, selectivity and in vivo efficacy were obtained.
Bicyclic piperazinone based thrombin inhibitors of general structure 2 were prepared and evaluated in vitro and in vivo. These inhibitors, having in common an electrophilic basic ...trans-cyclohexylamine P1 residue, displayed high thrombin affinity, high selectivity against trypsin and good in vivo efficacy in the rat arterial thrombosis model.
An efficient synthesis of constrained bicyclic peptidomimetics of (R)-Phe-Pro dipeptide is described. Such mimetics may provide an opportunity to develop inhibitors of thrombin possessing the desired ...pharmacological features.
A convenient synthesis of peptidomimetics of (R)-Phe-Pro dipeptide is described.
Peptidomimetic inhibitors of general structure
1 have been prepared. Optimization of the binding affinities of these compounds through variation of the P3 hydrophobic residue is described. Selected ...substituted bicylic lactams displayed interesting pharmacological profiles both in vitro and in vivo.
Design, synthesis, and SAR of low molecular weight peptidomimetic inhibitors of thrombin are described.
Inogatran is an effective and selective pseudopeptide inhibitor of thrombin that has been shown to be efficacious in a series of in vitro and in vivo models of thrombosis. Herein, we report an ...efficient and convergent chemical synthesis of Inogatran that is amenable to the preparation of multiple gram quantities.
Inogatran is an effective and selective pseudopeptide inhibitor of thrombin that has been shown to be efficacious in a series of in vitro and in vivo models of thrombosis. Herein, we report an efficient and convergent chemical synthesis of Inogatran that is amenable to the preparation of multiple gram quantities.
