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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H31N5O4
Molecular Weight 429.5126
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MELAGATRAN

SMILES

NC(=N)C1=CC=C(CNC(=O)[C@@H]2CCN2C(=O)[C@H](NCC(O)=O)C3CCCCC3)C=C1

InChI

InChIKey=DKWNMCUOEDMMIN-PKOBYXMFSA-N
InChI=1S/C22H31N5O4/c23-20(24)16-8-6-14(7-9-16)12-26-21(30)17-10-11-27(17)22(31)19(25-13-18(28)29)15-4-2-1-3-5-15/h6-9,15,17,19,25H,1-5,10-13H2,(H3,23,24)(H,26,30)(H,28,29)/t17-,19+/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16076267 | https://www.ncbi.nlm.nih.gov/pubmed/16025234 | https://www.ncbi.nlm.nih.gov/pubmed/17347079

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 is a prodrug that is rapidly converted after oral administration to the active compound melagatran. Melagatran is able to inhibit thrombin activity directly and quickly. The melagatran molecule binds to the arginine side pocket of thrombin, inactivating the thrombin. Following oral administration of ximelagatran, oral bioavailability (measured as melagatran) is 18% to 25%. Peak melagatran levels after a ximelagatran dose of 48 mg twice daily are achieved within approximately 2 hours. Ximelagatran is rapidly and extensively converted to melagatran in the liver and other tissues. This conversion is achieved by ester hydrolysis and reduction via two intermediate metabolites, hydroxymelagatran, and ethylmelagatran. The predominant compound in plasma is the active drug, melagatran. The elimination half-life of melagatran after an oral dose of ximelagatran is 2.5 to 4.3 hours.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
74.0 nM [IC50]
17300.0 nM [IC50]
20.0 µM [IC50]
2.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
EXANTA

Approved Use

Unknown
Preventing
EXANTA

Approved Use

Unknown
Primary
EXANTA

Approved Use

Unknown
Primary
EXANTA

Approved Use

Unknown
Preventing
EXANTA

Approved Use

Unknown
Preventing
EXANTA

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes.
1998 Jan
Pharmacokinetics, preliminary efficacy and safety of subcutaneous melagatran and oral ximelagatran : a multicentre study of thromboprophylaxis in elective abdominal surgery.
2004
New antithrombotics in the prevention of thromboembolic disease.
2005 Aug
Treating patients with venous thromboembolism: initial strategies and long-term secondary prevention.
2005 Aug
Ximelagatran (Exanta): alternative to warfarin?
2005 Jan
Ximelagatran for stroke prevention in atrial fibrillation.
2005 Jul
Ximelagatran compared with warfarin for the prevention of systemic embolism and stroke. An imputed placebo analysis.
2005 Mar
Optimising stroke prevention in non-valvular atrial fibrillation.
2006 Oct
Ximelagatran for treatment and prophylaxis of recurrent events in deep vein thrombosis.
2007 Jul
[Antithrombotic therapy in atrial fibrillation with ximelagatran: can it be an alternative to warfarin?].
2007 Mar
Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischaemic events: observations from the ESTEEM Trial.
2007 Mar
Direct thrombin inhibition and stroke prevention in elderly patients with atrial fibrillation: experience from the SPORTIF III and V Trials.
2007 Nov
Patents

Sample Use Guides

Ximelagatran is dosed twice daily (7). In patients with chronic nonvalvular atrial fibrillation, oral ximelagatran 36 mg twice daily has been shown to be effective. For VTE prophylaxis, two approaches to dosing ximelagatran have been used: monotherapy and combination therapy. A daily dose of 24 mg and 36 mg has been studied in patients undergoing knee arthroplasty. The first dose is given on the morning after surgery or at least 12 hours after surgery, and treatment is continued for 7 to 12 days. In patients undergoing total knee or hip replacement surgery, the most effective therapy has been a single dose of subcutaneous melagatran 2 mg just before surgery (knife-to-skin) followed by melagatran 3 mg subcutaneously after surgery and then oral ximelagatran 24 mg twice daily for a total treatment duration of 8 to 11 days.
Route of Administration: Oral
In Vitro Use Guide
The potent inhibition of thrombin by melagatran was demonstrated by a low inhibition constant (Ki) for thrombin (0.002 micromol/l) and prolongation of clotting time to twice the control value in coagulation assays at low concentrations (0.010, 0.59 and 2.2 micromol/l for thrombin time, activated partial thromboplastin time and prothrombin time, respectively). Furthermore, thrombin-induced platelet aggregation was inhibited at the same concentration (IC50-value 0.002 micromol/l) as the Ki-value for thrombin. In two assays of global fibrinolysis, inhibition was observed at a concentration of 1.1 micromol/l in a euglobulin plasma fraction model, while no inhibition was observed at a concentration of < or = 10 micromol/l in a plasma model.
Name Type Language
MELAGATRAN
INN   MART.   MI   WHO-DD  
INN  
Official Name English
melagatran [INN]
Common Name English
Glycine, N-[(1R)-2-[(2S)-2-[[[[4-(aminoiminomethyl)phenyl]methyl]amino]carbonyl]-1-azetidinyl]-1-cyclohexyl-2-oxoethyl]-
Systematic Name English
Melagatran [WHO-DD]
Common Name English
MELAGATRAN [MART.]
Common Name English
MELAGATRAN [MI]
Common Name English
N-[(1R)-2-[(2S)-2-[[[[4-(Aminoiminomethyl)phenyl]methyl]amino]carbonyl]-1-azetidinyl]-1-cyclohexyl-2-oxoethyl]glycine
Systematic Name English
Classification Tree Code System Code
WHO-ATC B01AE04
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
WHO-VATC QB01AE04
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
NCI_THESAURUS C263
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
Code System Code Type Description
DRUG BANK
DB13616
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
MERCK INDEX
m7149
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY Merck Index
CHEBI
43966
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
CAS
159776-70-2
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
NCI_THESAURUS
C66077
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
EPA CompTox
DTXSID30166724
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
SMS_ID
100000081464
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
ChEMBL
CHEMBL266349
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
INN
7414
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
MESH
C109573
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
EVMPD
SUB08718MIG
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
FDA UNII
2A9QP32MD4
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY
PUBCHEM
183797
Created by admin on Fri Dec 15 16:30:52 GMT 2023 , Edited by admin on Fri Dec 15 16:30:52 GMT 2023
PRIMARY