title: Synthesis of ximelagatran, melagatran, hydroxymelagatran, and ethylmelagatran in H-3 labeled form.
abstract: In support of a study designed to better understand the liver toxicity of ximelagatran, ximelagatran, and melagatran, hydroxymelagatran and ethylmelagatran were prepared in tritium labeled form. Incorporation of tritium was achieved by hydrogen isotope exchange using Crabtree's catalyst and later with N-heterocyclic containing Ir catalyst. The tritiated product was then converted into the four target compounds to afford them in high purity and specific activity.
authors.affiliation: Isotope Chemistry, DMPK, AstraZeneca Pharmaceuticals LP, 43183 Mölndal, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Simonsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Stenhagen
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ericsson
authors.forename: Charles S
authors.initials: CS
authors.lastname: Elmore
mesh_terms: D000578:Amidines / Q000138:chemical synthesis*; D000991:Antithrombins / Q000138:chemical synthesis*; D001384:Azetidines / Q000138:chemical synthesis*; D001596:Benzylamines / Q000138:chemical synthesis*; D007553:Isotope Labeling; D014316:Tritium / Q000737:chemistry*
chemical_list: D000578:Amidines; D000991:Antithrombins; D001384:Azetidines; D001596:Benzylamines; C479417:N-hydroxymelagatran; C479418:ethyl melagatran; D014316:Tritium; C109573:melagatran; C426686:ximelagatran
keywords: Hydrogen-isotope exchange; N-heterocyclic carbene; ethylmelagatran; hydroxymelagatran; melagatran; ximelagatran