Ximelagatran

Ximelagatran

Clinical data
Trade names	Exanta
Pregnancy category	Uncategorized
Routes of administration	Oral (tablets)
ATC code	B01AE05 (WHO)
Legal status
Legal status	Withdrawn from market
Pharmacokinetic data
Bioavailability	20%
Metabolism	to melagatran
Biological half-life	3–5 hours
Excretion	Renal (80%)
Identifiers
IUPAC name ethyl 2-[[(1R)-1-cyclohexyl-2- [(2S)-2-[[4-(N'-hydroxycarbamimidoyl) phenyl]methylcarbamoyl]azetidin-1-yl]- 2-oxo-ethyl]amino]acetate
CAS Number	192939-46-1 N
PubChem CID	9574101
IUPHAR/BPS	6381
DrugBank	DB04898 Y
ChemSpider	7848559 Y
UNII	49HFB70472
KEGG	D01981 Y
ChEMBL	CHEMBL522038 Y
Chemical and physical data
Formula	C24H35N5O5
Molar mass	473.57 g·mol−1 (429 g/mol after conversion)
3D model (Jmol)	Interactive image
SMILES O=C(NCc1ccc(C(=N\O)\N)cc1)[C@H]3N(C(=O)[C@H](NCC(=O)OCC)C2CCCCC2)CC3
InChI InChI=1S/C24H35N5O5/c1-2-34-20(30)15-26-21(17-6-4-3-5-7-17)24(32)29-13-12-19(29)23(31)27-14-16-8-10-18(11-9-16)22(25)28-33/h8-11,17,19,21,26,33H,2-7,12-15H2,1H3,(H2,25,28)(H,27,31)/t19-,21+/m0/s1 Y Key:ZXIBCJHYVWYIKI-PZJWPPBQSA-N Y
NY (what is this?)

Ximelagatran (Exanta or Exarta, H 376/95) is an anticoagulant that has been investigated extensively as a replacement for warfarin that would overcome the problematic dietary, drug interaction, and monitoring issues associated with warfarin therapy. In 2006, its manufacturer AstraZeneca announced that it would withdraw pending applications for marketing approval after reports of hepatotoxicity (liver damage) during trials, and discontinue its distribution in countries where the drug had been approved (Germany, Portugal, Sweden, Finland, Norway, Iceland, Austria, Denmark, France, Switzerland, Argentina and Brazil).

Ximelagatran, a direct thrombin inhibitor, was the first member of this class that can be taken orally. It acts solely by inhibiting the actions of thrombin. It is taken orally twice daily, and rapidly absorbed by the small intestine. Ximelagatran is a prodrug, being converted in vivo to the active agent melagatran. This conversion takes place in the liver and many other tissues through dealkylation and dehydroxylation (replacing the ethyl and hydroxyl groups with hydrogen).

Ximelagatran was expected to replace warfarin and sometimes aspirin and heparin in many therapeutic settings, including deep venous thrombosis, prevention of secondary venous thromboembolism and complications of atrial fibrillation such as stroke. The efficacy of ximelagatran for these indications had been well documented, except for non valvular atrial fibrillation.