162696-15-3Relevant articles and documents
Protein-Templated Formation of an Inhibitor of the Blood Coagulation Factor Xa through a Background-Free Amidation Reaction
Jaegle, Mike,Steinmetzer, Torsten,Rademann, J?rg
supporting information, p. 3718 - 3722 (2017/03/21)
Protein-templated reactions enable the target-guided formation of protein ligands from reactive fragments, ideally with no background reaction. Herein, we investigate the templated formation of amides. A nucleophilic fragment that binds to the coagulation factor Xa was incubated with the protein and thirteen differentially activated dipeptides. The protein induced a non-catalytic templated reaction for the phenyl and trifluoroethyl esters; the latter was shown to be a completely background-free reaction. Starting from two fragments with millimolar affinity, a 29 nm superadditive inhibitor of factor Xa was obtained. The fragment ligation reaction was detected with high sensitivity by an enzyme activity assay and by mass spectrometry. The reaction progress and autoinhibition of the templated reaction by the formed ligation product were determined, and the structure of the protein–inhibitor complex was elucidated.
Large scale preparation of protected 4-aminomethylbenzamidine. Application to the synthesis of the thrombin inhibitor, melagatran
Lila, Christine,Gloanec, Philippe,Cadet, Laurence,Herve, Yolande,Fournier, Jean,Leborgne, Fabrice,Verbeuren, Tony J.,De Nanteuil, Guillaume
, p. 4419 - 4429 (2007/10/03)
To allow the preparation of melagatran on a multigram scale, we have investigated several approaches for the synthesis of the key intermediate 4- aminomethylbenzamidine. The only industrially suitable pathway relies on the preparation of an N-hydroxyimino
