ethyl 2-{[(1R)-1-cyclohexyl-2-[(2S)-2-[({4-[(Z)-N'-hydroxycarbamimidoyl]phenyl}methyl)carbamoyl]azetidin-1-yl]-2-oxoethyl]amino}acetate

• ChemBase ID: 4399
• Molecular Formular: C24H35N5O5
• Molecular Mass: 473.5652
• Monoisotopic Mass: 473.26381925
• SMILES: O=C(N1[C@@H](CC1)C(=O)NCc1ccc(cc1)/C(=N/O)/N)[C@H](NCC(=O)OCC)C1CCCCC1
• Canonical SMILES: CCOC(=O)CN[C@@H](C(=O)N1CC[C@H]1C(=O)NCc1ccc(cc1)/C(=N/O)/N)C1CCCCC1
• 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
• InChIKey: ZXIBCJHYVWYIKI-PZJWPPBQSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: ethyl 2-{[(1R)-1-cyclohexyl-2-[(2S)-2-[({4-[(Z)-N'-hydroxycarbamimidoyl]phenyl}methyl)carbamoyl]azetidin-1-yl]-2-oxoethyl]amino}acetate
• IUPAC Traditional name: ximelagatran
• Brand Name: Exanta; Exarta
• Synonyms: H 376/95; ximelagatran; Ximelagatran

Database IDs

• CAS Number: 192939-46-1
• PubChem SID: 46509040; 160967831
• PubChem CID: 9574101

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.638632
• H Acceptors: 7
• H Donor: 4
• LogD (pH = 5.5): 0.5353352
• LogD (pH = 7.4): 0.8611465
• Log P: 0.8693069
• Molar Refractivity: 126.5662 cm^3
• Polarizability: 49.31325 Å^3
• Polar Surface Area: 146.35 Å^2
• Rotatable Bonds: 11
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.35
• LOG S: -3.75
• Solubility (Water): 8.45e-02 g/l

DETAILS

DrugBank - DB04898

• Drug Groups: approved; withdrawn; investigational
• Description: 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 not attempt to market ximelagatran after reports of hepatotoxicity (liver damage) during trials, and to discontinue its distribution in countries where the drug had been approved.
• Indication: For the treatment of acute deep vein thrombosis.
• Toxicity: Hepatotoxicity (liver damage) was reported during trials.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. 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).
• Absorption: Rapidly absorbed by the small intestine with an oral bioavailability of 20%.
• Half Life: 3-5 hours
• References: Eriksson H, Wahlander K, Gustafsson D, Welin LT, Frison L, Schulman S: A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I. J Thromb Haemost. 2003 Jan;1(1):41-7. [Pubmed] ; Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I19-26. [Pubmed] ; Francis CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, Peters GR, Roth AW, McElhattan J, Colwell CW Jr: Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med. 2003 Oct 30;349(18):1703-12. [Pubmed] ; Bergqvist D, Solhaug JH, Holmdahl L, Eriksson UG, Andersson M, Boberg B, Ogren M: Pharmacokinetics, preliminary efficacy and safety of subcutaneous melagatran and oral ximelagatran : a multicentre study of thromboprophylaxis in elective abdominal surgery. Clin Drug Investig. 2004;24(3):127-36. [Pubmed] ; Koscielny J, Kiesewetter H, Jorg I, Harenberg J: Ximelagatran for treatment and prophylaxis of recurrent events in deep vein thrombosis. Clin Appl Thromb Hemost. 2007 Jul;13(3):299-307. [Pubmed]
• External Links: Wikipedia

REFERENCES

• Eriksson H, Wahlander K, Gustafsson D, Welin LT, Frison L, Schulman S: A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I. J Thromb Haemost. 2003 Jan;1(1):41-7. Pubmed
• Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I19-26. Pubmed
• Francis CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, Peters GR, Roth AW, McElhattan J, Colwell CW Jr: Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med. 2003 Oct 30;349(18):1703-12. Pubmed
• Bergqvist D, Solhaug JH, Holmdahl L, Eriksson UG, Andersson M, Boberg B, Ogren M: Pharmacokinetics, preliminary efficacy and safety of subcutaneous melagatran and oral ximelagatran : a multicentre study of thromboprophylaxis in elective abdominal surgery. Clin Drug Investig. 2004;24(3):127-36. Pubmed
• Koscielny J, Kiesewetter H, Jorg I, Harenberg J: Ximelagatran for treatment and prophylaxis of recurrent events in deep vein thrombosis. Clin Appl Thromb Hemost. 2007 Jul;13(3):299-307. Pubmed