NAPSAGATRAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H34N6O6S.H2O
Molecular Weight	576.665
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.NC(=N)N1CCC[C@@H](CNC(=O)C[C@H](NS(=O)(=O)C2=CC=C3C=CC=CC3=C2)C(=O)N(CC(O)=O)C4CC4)C1

InChI

InChIKey=TYAMPCPJIDBUQW-ZLLYMXMVSA-N

InChI=1S/C26H34N6O6S.H2O/c27-26(28)31-11-3-4-17(15-31)14-29-23(33)13-22(25(36)32(16-24(34)35)20-8-9-20)30-39(37,38)21-10-7-18-5-1-2-6-19(18)12-21;/h1-2,5-7,10,12,17,20,22,30H,3-4,8-9,11,13-16H2,(H3,27,28)(H,29,33)(H,34,35);1H2/t17-,22-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800004026 | https://www.ncbi.nlm.nih.gov/pubmed/7578898 | https://www.ncbi.nlm.nih.gov/pubmed/7893925

Napsagatran [RO 466240], a reversible and highly selective thrombin inhibitor, was in development with Roche for use in myocardial infarction and thrombosis. Napsagatran efficiently inhibits and delays thrombin generation in human coagulating plasma. This reduced thrombin generation might be caused by inhibition of thrombin-mediated feedback reactions during blood coagulation. Ro 46-6240 inhibited clot-bound thrombin three times more potently than fluid-phase thrombin (IC50 19 vs 56 ng/ml) while hirudin was two times (IC50 8 vs 3 ng/ml) and heparin six times (IC50 1,205 vs 200 ng/ml) less active against clot-bound thrombin compared with fluid-phase thrombin.

Originator

Approval Year

PubMed

Title	Date	PubMed
Effects of napsagatran (Ro 46-6240), a new synthetic thrombin inhibitor and of heparin in a canine model of coronary artery thrombosis: comparison with an ex vivo annular perfusion chamber model.	1996 Apr	8613969
Interspecies pharmacokinetic comparisons and allometric scaling of napsagatran, a low molecular weight thrombin inhibitor.	1999 Jan	10197423
The effect of warfarin on the pharmacokinetics and pharmacodynamics of napsagatran in healthy male volunteers.	2001 Apr	11372586

Patents

Sample Use Guides

In Vivo Use Guide

One hundred and ten patients with acute proximal deep-vein thrombosis were randomized in a sequential dose-finding design, to receive continuous intravenous infusion of napsagatran, a novel synthetic thrombin-inhibitor, at a fixed dose of 5 mg/h (n = 37) or 9 mg/h (n = 26), or APTT-adjusted unfractionated heparin (n = 47).

Route of Administration: Intravenous

In Vitro Use Guide

Napsagatran [RO 466240] was nearly as potent as r-hirudin for inhibiting extrinsic thrombin generation (IC50 418 vs 229 nM) and intrinsic thrombin generation (IC50 463 vs 343 nM) despite a much lower affinity of Ro 466240 for thrombin (Ki apparent: 0.3 nM) in a purified buffer system.

Name

Type

Language

NAPSAGATRAN

Official Name

English

NAPSAGATRAN [USAN]

Common Name

English

RO 46-6240/010

Code

English

RO-46-6240/010

Code

English

GLYCINE, N-(N-((1-(AMINOIMINOMETHYL)-3-PIPERIDINYL)METHYL)-N(SUP 2)-(2-NAPHTHALENYLSULFONYL)-L-ASPARAGINYL)-N-CYCLOPROPYL-, MONOHYDRATE, (S)-

Common Name

English

RO-46-6240

Code

English

N-(N(SUP 4)-(((3S-1-AMIDINO-3-PIPERIDYL)METHYL)-N(SUP 2)-(2-NAPHTHYLSULFONYL)-L-ASPARAGINYL)-N-CYCLOPROPYLGLYCINE MONOHYDRATE

Common Name

English

RO-466240010

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C263