193965-54-7Relevant academic research and scientific papers
Antithrombotic agents
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Page column 23, (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.
Thrombin inhibitors
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, (2008/06/13)
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 defined compounds of formula I as thrombin inhibitors.
Antithrombotic Agents
-
, (2008/06/13)
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.
Antithrombotic agents
-
, (2008/06/13)
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.
Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 4. SAR studies on the conformationally restricted C3-side chain of hydroxybenzo[b]thiophenes
Takeuchi, Kumiko,Kohn, Todd J.,Sall, Daniel J.,Denney, Michael L.,McCowan, Jefferson R.,Smith, Gerry F.,Gifford-Moore, Donetta S.
, p. 759 - 764 (2007/10/03)
A novel series of benzo[b]thiophene diamine thrombin inhibitors with a conformationally restricted C3-side chain 3 was investigated. The constrained C3-side chain by a cyclohexyl ring contributed to not only an additive but also a synergistic effect on the thrombin inhibitory activity. The SAR studies resulted in the discovery of a potent thrombin inhibitor 27 that was over 750-fold more potent than the initial lead compound 1.
