Ximelagatran is a synthetic oral anticoagulant and prodrug of melagatran. It belongs to the direct thrombin inhibitor class and was developed as an orally administered anticoagulant. Ximelagatran is chemically different from traditional vitamin K antagonists because its anticoagulant activity is achieved through direct inhibition of thrombin rather than interference with vitamin K metabolism.
The molecular formula of Ximelagatran is C24H35N5O5, with a molecular weight of approximately 473.6 g/mol. Its CAS Number is 192939-46-1, and its FDA Global Substance Registration System UNII is 49HFB70472.
Ximelagatran is structurally related to melagatran. It can be described as a modified melagatran structure in which the carboxylic acid has been converted to an ethyl ester and the amidine functionality has been converted to an amidoxime. These structural modifications were designed to improve oral absorption and allow conversion to the active anticoagulant melagatran after administration.
The molecule contains an azetidine ring, cyclohexyl group, phenyl group, amide functionalities and an amidoxime group. Its molecular structure provides the functionality required for conversion to the active direct thrombin inhibitor.
Ximelagatran was developed as an oral prodrug of melagatran. Following administration, ximelagatran undergoes metabolic conversion to melagatran, which directly inhibits thrombin.
Thrombin is a key serine protease in the coagulation cascade. It converts fibrinogen to fibrin and contributes to amplification of coagulation. Direct inhibition of thrombin therefore reduces thrombin-mediated coagulation activity.
Because Ximelagatran was designed as an orally available direct thrombin inhibitor, it represented a different anticoagulation approach from warfarin and other vitamin K antagonists.
Ximelagatran is identified by the following principal chemical characteristics. PubChem lists the molecular formula as C24H35N5O5 and molecular weight as 473.6 g/mol. The calculated exact mass is approximately 473.2638 Da.
The compound has four hydrogen-bond donors and seven hydrogen-bond acceptors, with a calculated topological polar surface area of approximately 146 Ų.
Ximelagatran is described as a solid powder. Reported sources describe the material as white to beige or off-white powder and as hygroscopic. Reported melting-point values vary by source, with values around 65–75°C appearing in chemical databases and research-product information.
Because these values are not presented as a current pharmacopoeial release specification, they should be treated as physicochemical reference information rather than a universal pharmaceutical acceptance criterion.
Available chemical-property sources indicate that Ximelagatran has measurable but relatively limited aqueous solubility. HMDB reports a calculated/recorded water-solubility value of approximately 0.084 g/L, equivalent to approximately 84 mg/L.
Research-product information also describes Ximelagatran as soluble in methanol and chloroform, while another current chemical listing reports high solubility in DMSO and measurable solubility in methanol.
Ximelagatran has been extensively studied using chromatographic techniques because assay and related-substance determination are important for pharmaceutical analysis.
A peer-reviewed pharmaceutical-analysis study developed and validated a capillary electrophoresis method for determination of Ximelagatran assay and related substances in both drug substance and tablets. The study compared the method with an established gradient liquid-chromatography method and demonstrated suitable selectivity, accuracy, precision, linearity and robustness.
The published method was capable of separating Ximelagatran from known related substances and was reported to quantify potential related substances at approximately the 0.05% level.
A commercially available research reference material is listed with an assay of ≥98% by HPLC. This value is useful as an analytical reference, but it should not be represented as a current USP, BP or Ph. Eur. pharmaceutical-release specification because no current public pharmacopoeial monograph was identified.
For commercial API manufacturing, the actual release assay should therefore be established against the applicable validated manufacturer specification and analytical method.
Related-substance control is an important analytical attribute for Ximelagatran. Published pharmaceutical research specifically describes validated chromatographic and capillary-electrophoresis procedures for separating Ximelagatran from known related substances.
However, publicly accessible sources reviewed for this page do not provide a verified current pharmaceutical API acceptance limit for each individual impurity or for total impurities. Accordingly, numerical impurity limits have not been invented for the CMS specification.
Ximelagatran was developed as an oral anticoagulant and was marketed in Europe under the brand name Exanta. It was not approved in the United States. Regulatory evaluation identified significant concerns regarding severe liver injury during longer-term treatment.
FDA documents describe severe liver injury in long-term ximelagatran trials and report that the sponsor subsequently withdrew ximelagatran from worldwide marketing.
For this reason, the product page should describe Ximelagatran as a historical/discontinued anticoagulant API and research/reference compound, rather than presenting it as a currently approved marketed anticoagulant.
Manufacturing of Ximelagatran as a chemical API requires appropriate control of starting materials, intermediates, reaction conditions, purification and final product quality. Analytical characterization can include identity testing, chromatographic assay, related-substance analysis, residual-solvent testing, water determination and physical-property characterization.
For research and analytical applications, validated chromatographic procedures are particularly relevant because Ximelagatran has several structurally related compounds that require adequate chromatographic separation. Published work demonstrates both LC and capillary-electrophoresis approaches for this purpose.
Ximelagatran has been described as hygroscopic, so protection from excessive moisture is appropriate during storage and handling. A research-product source recommends storage at −20°C.
For pharmaceutical API applications, the final storage condition should follow the validated stability data and approved or manufacturer-specific packaging and storage specification.
Ximelagatran is a specialized direct-thrombin-inhibitor prodrug API with historical pharmaceutical significance. For pharmaceutical research, analytical development and API-related requirements, appropriate quality documentation, analytical characterization and regulatory-status assessment should accompany the material.
Swapnroop Drugs & Pharmaceuticals can present Ximelagatran as an API and pharmaceutical research compound with its chemical identity, analytical characteristics and available quality documentation clearly defined.
Ximelagatran is a synthetic oral prodrug of melagatran and belongs to the direct thrombin inhibitor class. It has the molecular formula C24H35N5O5, molecular weight 473.6 g/mol, and CAS Number 192939-46-1.
Published pharmaceutical-analysis literature confirms validated chromatographic approaches for Ximelagatran assay and related-substance determination.
Because Ximelagatran was withdrawn following significant liver-safety concerns, the product should be described accurately as a historical/discontinued pharmaceutical compound, not as a currently approved marketed anticoagulant.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | NLT 98.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.5% |
| Melting Point | 65–75°C |