CAS 192939-46-1|ethyl 2-{[(1R)-1-cyclohexyl-2-[(2S)-2-[({4-[(Z)-N'-hydroxycarbamimidoyl]phenyl}methyl)carbamoyl]azetidin-1-yl]-2-oxoethyl]amino}acetate|H 376/95|Exanta|Ximelagatran|ximelagatran|xime...

General Information

Structure

Molecular Formula

C₂₄H₃₅N₅O₅

Molecular Mass

473.5652

Exact Mass

473.26381925

Charge

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

Canonic Smiles

CCOC(=O)CN[C@@H](C(=O)N1CC[C@H]1C(=O)NCc1ccc(cc1)/C(=N/O)/N)C1CCCCC1

Isomeric Smiles

O=C(N1[C@@H](CC1)C(=O)NCc1ccc(cc1)/C(=N/O)/N)[C@H](NCC(=O)OCC)C1CCCCC1

Calculated Properties

JChem

LogD (pH = 7.4)

0.84

LogD (pH = 5.5)

0.53

Log P

0.87

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

8.70

Polar Surface Area

146.35

Polarizability

52.43

Molar Refractivity

126.57

LOG S

-4.95

Data Source

Academic Data

Data Source

Names and Identifiers

IUPAC name

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

Synonyms

H 376/95XimelagatranximelagatranExantaH 376/95Exartaximelagatran (oxime form)ximelagatranH 37695ethyl 2-[[(1R)-1-cyclohexyl-2- [(2S)-2-[[4-(N'-hydroxycarbamimidoyl) phenyl]methylcarbamoyl]azetidin-1-yl]- 2-oxo-ethyl]amino]acetateH 376-95

Brand Name

ExantaExarta

IUPAC Traditional name

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

International Nonproprietary Name (INN)

ximelagatranumximelagatran

Names and Identifiers

Registration numbers

PubChem CID

9574101

PubChem SID

16096783146509040160645186

CAS Number

192939-46-1

PubMed Citation Links

167678161548795928338626161239121284659517636192165116072002026916106594160841461731946919028773

SureChEMBL Database

SCHEMBL4845SCHEMBL19065093SCHEMBL15908919

ACToR Database

192939-46-1

KEGG DRUG Database

D01981

MetaboLights Database

MTBLS1693MTBLS2871MTBLS591

CHEBI ID

CHEBI:65172

DrugBank ID

DB04898

CHEMBL

CHEMBL522038

BRENDA Ligand Database

16747175362

GeneOntology Database

Reaxys Registry

Wikipedia Title

BKMS React Database

Drug Central Database

2,852

BindingDB Database

50505290

CompTox Database

DTXSID5049075

Registration numbers

Properties

No Data Available

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Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule 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]

ChEBI

CHEBI:65172

A member of the class of azetidines that is melagatran in which the carboxylic acid group has been converted to the corresponding ethyl ester and in which the amidine group has been converted into the corresponding amidoxime. A prodrug for melagatran, ximelagatran was the first orally available direct thrombin inhibitor to be brought to market as an anticoagulant, but was withdrawn in 2006 following reports of it causing liver damage.

Molecule Details

References

PubChem Literature

From Data Sources

• Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I19-26. 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

References

Bioactivity

PubChem BioAssay

Bioactivity

Navigation

General Information

Calculated Properties

• RDKit

• JChem

Data Source

• Academic Data

Names and Identifiers

• IUPAC name

• Synonyms

• Brand Name

• IUPAC Traditional name

• International Nonproprietary Name (INN)

Names and Identifiers

Registration numbers

• PubChem CID

• PubChem SID

• CAS Number

• PubMed Citation Links

• SureChEMBL Database

• ACToR Database

• KEGG DRUG Database

• MetaboLights Database

• CHEBI ID

• DrugBank ID

• CHEMBL

• BRENDA Ligand Database

• GeneOntology Database

• Reaxys Registry

• Wikipedia Title

• BKMS React Database

• Drug Central Database

• BindingDB Database

• CompTox Database

• DrugBank

• ChEBI

References

• PubChem Literature

• From Data Sources

Bioactivity

• PubChem BioAssay

IUPAC name

Synonyms

Brand Name

ExantaExarta

IUPAC Traditional name

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

International Nonproprietary Name (INN)

ximelagatranumximelagatran

CAS Number

192939-46-1

ACToR Database

192939-46-1

KEGG DRUG Database

D01981

MetaboLights Database

MTBLS1693MTBLS2871MTBLS591

CHEBI ID

CHEBI:65172

BRENDA Ligand Database

16747175362

GeneOntology Database

Reaxys Registry

Wikipedia Title

BKMS React Database

Drug Central Database

BindingDB Database

CompTox Database

DB04898

Drug Groups

approved; withdrawn; investigational

Description

Indication

For the treatment of acute deep vein thrombosis.

Toxicity

Hepatotoxicity (liver damage) was reported during trials.

Affected Organisms

Humans and other mammals

Biotransformation

Absorption

Rapidly absorbed by the small intestine with an oral bioavailability of 20%.

Half Life

3-5 hours

References

• Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I19-26. [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]

ChEBI

CHEBI:65172

From Data Sources

• Weitz JI: New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31;110(9 Suppl 1):I19-26. 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

Molecule

ID:4399