162694-63-5Relevant articles and documents
The fourth molybdenum containing enzyme mARC: Cloning and involvement in the activation of N-hydroxylated prodrugs
Gruenewald, Sanja,Wahl, Bettina,Bittner, Florian,Hungeling, Helen,Kanzow, Stephanie,Kotthaus, Joscha,Schwering, Ulrike,Mendel, Ralf R.,Clement, Bernd
scheme or table, p. 8173 - 8177 (2009/12/07)
The recently discovered mammalian molybdoprotein mARC1 is capable of reducing N-hydroxylated compounds. Upon reconstitution with cytochrome b 5 and b5 reductase, benzamidoxime, pentamidine, and diminazene amidoximes, N-hydroxymelagatran, guanoxabenz, and N-hydroxydebrisoquine are efficiently reduced. These substances are amidoxime/N-hydroxyguanidine prodrugs, leading to improved bioavailability compared to the active amidines/guanidines. Thus, the recombinant enzyme allows prediction about in vivo reduction of N-hydroxylated prodrugs. Furthermore, the prodrug principle is not dependent on cytochrome P450 enzymes.
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
