Ximelagatran/Melagatran

Evans, Hannah C; Perry, Caroline M.; Faulds, Diana

doi:10.2165/00003495-200464060-00010

Cited by 25 publications

(3 citation statements)

References 44 publications

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“…Ximelagatran was then evaluated in large clinical trials for stroke prevention in atrial fibrillation as well as for VTE treatment and prevention and proved to be as effective as the comparator (either VKA or LMWH) with a similar rate of bleeding. [49][50][51][52][53] In 2004, ximelagatran was briefly approved for VTE prophylaxis after orthopaedic surgery in Europe but not in the United States, because of reports in the trials of rare but serious hepatic toxicity. 54,55 In 2006, ximelagatran was withdrawn from clinical use in Europe.…”

Section: Direct Oral Anticoagulantsmentioning

confidence: 99%

Clinical Studies with Anticoagulants that Have Changed Clinical Practice

Hirsh

Vries

Eikelboom

et al. 2023

Semin Thromb Hemost

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Anticoagulant therapy is the cornerstone of treatment and prevention of arterial and venous thromboembolism. Taking a historical perspective, starting in the 1960s, and progressing through to 2022, we discuss key clinical trials of anticoagulants that have changed clinical practice, and examine obstacles encountered in bringing these anticoagulants to the clinic. The design of some of the early studies that shaped clinical practice was poor by current standards, but their results were influential because nothing better was available. Both heparin and vitamin K antagonists had been in clinical use for several decades before well-designed trials in the 1980s optimized their dosing and enhanced their safety and efficacy. Low-molecular-weight heparin then replaced unfractionated heparin because it had a more predictable dose–response and a longer half-life, thereby allowing it to be used conveniently in out-of-hospital settings. More recently, direct oral anticoagulants became the oral anticoagulants of choice for most indications because they were shown to be at least as safe and effective as vitamin K antagonists when used in fixed doses without the need for laboratory monitoring. The design of the trials that led to the approval of the direct oral anticoagulants was excellent, but further studies are required to optimize their dosing in selected patients who were underrepresented in these trials.

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Section: Direct Oral Anticoagulantsmentioning

confidence: 99%

Clinical Studies with Anticoagulants that Have Changed Clinical Practice

Hirsh

Vries

Eikelboom

et al. 2023

Semin Thromb Hemost

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“…Ximelagatran, a prodrug of melagatran, is the first oral DTI, which represents a new era of anticoagulation for the prevention and treatment of VTE. Although it was withdrawn from the market due to a risk of significant hepatotoxicity, ximelagatran demonstrated improved antithrombotic efficacy when compared with traditional anticoagulation therapies ( Evans et al ., 2004 ). A few years later, dabigatran etexilate, the second oral DTI, was developed with some improvements such as no risk of hepatotoxicity and low potential for food or drug interactions.…”

Section: New Anticoagulantsmentioning

confidence: 99%

New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism

Kim

Lim

Gwak

2017

Biomolecules & Therapeutics

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Anticoagulant drugs, like vitamin K antagonists and heparin, have been the mainstay for the treatment and prevention of venous thromboembolic disease for many years. Although effective if appropriately used, traditional anticoagulants have several limitations such as unpredictable pharmacologic and pharmacokinetic responses and various adverse effects including serious bleeding complications. New oral anticoagulants have recently emerged as an alternative because of their rapid onset/offset of action, predictable linear dose-response relationships and fewer drug interactions. However, they are still associated with problems such as bleeding, lack of reversal agents and standard laboratory monitoring. In an attempt to overcome these drawbacks, key steps of the hemostatic pathway are investigated as targets for anticoagulation. Here we reviewed the traditional and new anticoagulants with respect to their targets in the coagulation cascade, along with their therapeutic advantages and disadvantages. In addition, investigational anticoagulant drugs currently in the development stages were introduced.

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“…Chiral azetidine-2-carboxylic acid, the first known example of naturally occurring azetidines, [8] and their derivatives (potential products from reduction of 2-azetine-carboxylates) are structural units of several natural products [9] and the thrombin inhibitor melagatran [10] (Figure 1). Va rious methods have been used for their preparation, [11] but all of them are multistep syntheses from chiral reactants that provide access only to mono-or disubstituted azetidine-2-carboxylic acids and their derivatives.Herein, we report arobust methodology for the highly enantioselective synthesis of 2-azetine-carboxylates catalyzed by copper(I) with chiral sabox ligand and their stereoselective hydrogenation to form as ingle stereoisomer of tetrasubstituted azetidine-2-carboxylate derivatives (Scheme 1c).…”

mentioning

confidence: 99%

Synthesis of Chiral Tetrasubstituted Azetidines from Donor–Acceptor Azetines via Asymmetric Copper(I)‐Catalyzed Imido‐Ylide [3+1]‐Cycloaddition with Metallo‐Enolcarbenes

et al. 2019

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The all‐cis stereoisomers of tetrasubstituted azetidine‐2‐carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl‐protected Z‐γ‐substituted enoldiazoacetates and imido‐sulfur ylides by asymmetric [3+1]‐cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p‐methoxybenzyl azetine‐2‐carboxylates occurs with both hydrogen addition to the C=C bond and hydrogenolysis of the ester.

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Ximelagatran/Melagatran

Cited by 25 publications

References 44 publications

Clinical Studies with Anticoagulants that Have Changed Clinical Practice

Clinical Studies with Anticoagulants that Have Changed Clinical Practice

New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism

Synthesis of Chiral Tetrasubstituted Azetidines from Donor–Acceptor Azetines via Asymmetric Copper(I)‐Catalyzed Imido‐Ylide [3+1]‐Cycloaddition with Metallo‐Enolcarbenes

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