LETAXABAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H26ClN3O5S
Molecular Weight	479.977
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H](CS(=O)(=O)C1=CC=C2C=C(Cl)C=CC2=C1)C(=O)N3CCC(CC3)N4CCCNC4=O

InChI

InChIKey=GEHAEMCVKDPMKO-HXUWFJFHSA-N

InChI=1S/C22H26ClN3O5S/c23-17-4-2-16-13-19(5-3-15(16)12-17)32(30,31)14-20(27)21(28)25-10-6-18(7-11-25)26-9-1-8-24-22(26)29/h2-5,12-13,18,20,27H,1,6-11,14H2,(H,24,29)/t20-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30568593 | https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C96541 | https://www.pharmacodia.com/yaodu/html/v1/chemicals/f67fe69d3660b4d35a731817b538b21d.html | https://adisinsight.springer.com/drugs/800027537

Letaxaban is an orally active, tetrahydropyrimidin-2(1H)-one derivative and inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Letaxaban may have anti-inflammatory potential in addition to its anti-thrombotic effects. Letaxaban had been in phase II clinical trials by Takeda for the treatment of venous thromboembolism (VTE). However, this research has been discontinued. Takeda had discontinued their phase II clinical trials for the treatment of acute coronary syndrome (ACS) since the results failed to meet the target efficacy and safety profile.

Approval Year

PubMed

Title	Date	PubMed
Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development.	2009	19071881
Factor Xa inhibitors--new anticoagulants for secondary haemostasis.	2009 Aug	19644596
New anticoagulants: focus on venous thromboembolism.	2009 Jul	19601856
Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats.	2010 Aug	20452654
Antithrombotic and anticoagulant profiles of TAK-442, a novel factor Xa inhibitor, in a rabbit model of venous thrombosis.	2010 Aug	20410831
A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery.	2010 Dec	20886185
Discovery of a tetrahydropyrimidin-2(1H)-one derivative (TAK-442) as a potent, selective, and orally active factor Xa inhibitor.	2010 May 13	20355714
Differential effects of TAK-442, a novel orally active direct factor Xa inhibitor, and ximelagatran, a thrombin inhibitor, on factor V-mediated feedback on coagulation cascade and bleeding.	2010 Sep	20664909
Effects of fondaparinux and a direct factor Xa inhibitor TAK-442 on platelet-associated prothrombinase in the balloon-injured artery of rats.	2011 Feb	21052010
Novel oral anticoagulants in the treatment of acute coronary syndromes: is there any room for new anticoagulants?	2012 Aug	22564121
Development and clinical applications of novel oral anticoagulants. Part II. Drugs under clinical investigation.	2012 Jun	22742650
Efficacy and toxicity of factor Xa inhibitors.	2013	23683607
Investigational anticoagulants for hematological conditions: a new generation of therapies.	2013 Oct	23876036
Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome.	2014 Jun	24671450
Role of novel and emerging oral anticoagulants for secondary prevention of acute coronary syndromes.	2014 Jun	24338703
Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors.	2016 Feb 4	26861270
TAK-442, a Direct Factor Xa Inhibitor, Inhibits Monocyte Chemoattractant Protein 1 Production in Endothelial Cells via Involvement of Protease-Activated Receptor 1.	2018	30568593
Anti-thrombotic effect of a factor Xa inhibitor TAK-442 in a rabbit model of arteriovenous shunt thrombosis stimulated with tissue factor.	2018 Oct 30	30376878

Patents

Sample Use Guides

In Vivo Use Guide

Doses of Letaxaban escalated from 10 mg BID, 20 mg twice-daily (BID), or 40 mg once-daily (QD) in stage 1; to 40 mg BID, 80 mg QD, or 80 mg BID in stage 2; and to 160 mg QD or 120 mg BID in stage 3.

Route of Administration: Oral

Name

Type

Language

LETAXABAN

Official Name

English

2(1H)-PYRIMIDINONE, 1-(1-((2S)-3-((6-CHLORO-2-NAPHTHALENYL)SULFONYL)-2-HYDROXY-1-OXOPROPYL)-4-PIPERIDINYL)TETRAHYDRO-

Systematic Name

English

1-(1-{(2S)-3-[(6-Chloronaphthalen-2-yl)sulfonyl]-2-hydroxypropanoyl}piperidin-4-yl)tetrahydropyrimidin-2(1H)-one

Systematic Name

English

PIPERIDINE, 1-((2S)-3-((6-CHLORO-2-NAPHTHALENYL)SULFONYL)-2-HYDROXY-1-OXOPROPYL)-4-(TETRAHYDRO-2-OXO-1(2H)-PYRIMIDINYL)-

Systematic Name

English

LETAXABAN [USAN]

Common Name

English

TAK442

Code

English

letaxaban [INN]

Common Name

English

Letaxaban [WHO-DD]

Common Name

English

TAK-442

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C29750