193966-49-3Relevant academic research and scientific papers
Antithrombotic agents
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Page column 44, (2010/01/31)
This application relates to novel compounds of formula (I) (and their pharmaceutically acceptable salts), as defined herein, processes and intermediates for their preparation, pharmaceutical formulations comprising the novel compounds of formula (I), and the use of the compounds of formula (I) as thrombin inhibitors.
Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 5. Potency, efficacy, and pharmacokinetic properties of modified C-3 side chain derivatives
Sall, Daniel J.,Bailey, Dianna L.,Bastian, Jolie A.,Buben, John A.,Chirgadze, Nickolay Y.,Clemens-Smith, Amy C.,Denney, Michael L.,Fisher, Matthew J.,Giera, Deborah D.,Gifford-Moore, Donetta S.,Harper, Richard W.,Johnson, Lea M.,Klimkowski, Valentine J.,Kohn, Todd J.,Lin, Ho-Shen,McCowan, Jefferson R.,Palkowitz, Alan D.,Richett, Michael E.,Smith, Gerald F.,Snyder, David W.,Takeuchi, Kumiko,Toth, John E.,Zhang, Minsheng
, p. 649 - 663 (2007/10/03)
A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit la led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271 x 106 L/mol, respectively) represent 2200- and 2900-fold increases in potency over the starting lead la. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of derivatives 28c and 31c were determined, and they compare favorably with the clinical agent H-R-1-[4aS,- 8aS]perhydroisoquinolyl-prolyl-arginyl aldehyde (D-Piq-Pro-Arg-H; 32). The more potent members of this series have been studied in an arterial/venous shunt (AV shunt) model of thrombosis and were found to be efficacious in reducing clot formation. However, their efficacy is currently limited by their rapid and extensive distribution following administration.
Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 3. Enhancing activity by imposing conformational restriction in the C-4'' side chain
Bastian, Jolie A.,Chirgadze, Nickolay,Denney, Michael L.,Gifford-Moore, Donetta S.,Sall, Daniel J.,Smith, Gerald F.,Wikel, James H.
, p. 363 - 368 (2007/10/03)
The preparation and biological evaluation of a series of benzo[b]thiophene diamine thrombin inhibitors possessing conformationally restricted C-4'' linkers are reported. Compared to the parent compounds 1a/b, the unsaturated derivatives 3a/b exhibited a m
