Enantiomeric characterization and structure elucidation of Otamixaban

Shen, Jian; Yang, Jiping; Heyse, Winfried; Schweitzer, Harald; Nagel, Norbert; Andert, Doris; Zhu, Chengyue; Morrison, Vincent; Nemeth, Gregory A.; Chen, Teng‐Man; Zhao, Zhicheng; Ayers, Timothy A.; Choi, Yong‐Mi

doi:10.1016/j.jpha.2013.10.001

Cited by 6 publications

(4 citation statements)

References 17 publications

(25 reference statements)

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“…Otamixaban is a potent FXa inhibitor that was developed by Shen et al 51 Steg et al performed a double-blind, activecontrolled superiority trial including over 13,000 patients with non-ST elevation acute coronary syndrome, undergoing early invasive revascularization. 52 Patients were randomized to receive 60 IU/kg UFH in bolusfollowed by 12 IU/kg/hour infusion (plus eptifibatide in those undergoing percutaneous coronary intervention) or 0.080 mg/kg intravenous bolus of otamixaban followed by 0.140 mg/kg per hour otamixaban infusion.…”

Section: Direct Oral Anticoagulants Discontinuedmentioning

confidence: 99%

Current and Emerging Direct Oral Anticoagulants: State-of-the-Art

Lippi

Gosselin

Favaloro

2019

Semin Thromb Hemost

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Anticoagulant drugs comprise a specific subcategory of antithrombotic agents that act to inhibit blood coagulation at various stages, reducing clot development and ultimately lowering the risk of developing new-onset or recurrent thrombosis. Although the long history of anticoagulant drugs has been characteristically shaped by coumarin and heparin derivatives, a new generation of direct oral anticoagulants (DOACs), which specifically inhibit thrombin or activated factor X, combine many advantages of their progenitor drugs, and hence are prepotently revolutionizing the landscape of antithrombotic therapy. Several drugs (apixaban [BMS-562247], dabigatran [BIBR953], edoxaban [DU-1766], rivaroxaban [BAY 59–7939]) have already received widespread approval by national or supranational medicinal agencies. This narrative article provides a state-of-the-art for these and for several other DOACs at different stages of clinical evaluation (betrixaban, darexaban, eribaxaban, letaxaban, nokxaban), and certain others whose development has been discontinued (AZD-0837, fidexaban, LY517717, odiparcil, otamixaban, TTP889, and ximelagatran). What clearly emerges from our analysis is that DOACs sharing very similar mechanisms of action are still characterized by different efficacy and safety profiles. This not only depends on biochemical, biological, and pharmacokinetic characteristics, but also on lack of standardization between different clinical trials in terms of targeted disease, patient recruitment, sample size, duration and endpoints, as well as lack of harmonization around procedures used for drug licensing. These factors contribute to challenging the minds of physicians, who may find difficulty navigating their way through multiple indications, different pharmacological profiles, various side effects, and specific drug-to-drug interactions. Such considerations also burden laboratory professionals, who may face organizational and economic challenges in developing and/or implementing multiple assays to assess the pharmacodynamics (effect on coagulation) or pharmacokinetics (drug levels) of DOACs.

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Section: Direct Oral Anticoagulants Discontinuedmentioning

confidence: 99%

Current and Emerging Direct Oral Anticoagulants: State-of-the-Art

Lippi

Gosselin

Favaloro

2019

Semin Thromb Hemost

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“…Most of the reported chiroptical spectral analyses for chiral drugs were accomplished via visual spectral analyses. A table summarizing the chiral drugs whose ACs were investigated [34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90] using chiroptical spectroscopic methods are summarized in Table 1. Occasional reviews have also highlighted some of these chiral drugs [42,65,91,92].…”

Section: Chiroptical Spectroscopic Toolsmentioning

confidence: 99%

Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy

Polavarapu

2016

Molecules

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Chiroptical spectroscopy has emerged as a promising tool for the determination of absolute configurations and predominant conformations of chiral molecules in academic laboratories. This promise has led to the adaption of chiroptical spectroscopic methods as valuable tools in chiral drug discovery research programs of the pharmaceutical industry. Most major pharmaceutical companies have invested in in-house chiroptical spectroscopy applications and reported successful outcomes. In the context of continuously increasing applications of chiroptical spectroscopy for chiral molecular structure determination, a review of recent developments and applications for chiral drugs is presented in this manuscript.

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“…Identifying between d and l enantiomers and their purity are of important scientific interest. Widely used analytical techniques to differentiate between enantiomers are optical rotation, circular dichroism (CD), and high-performance liquid chromatography. − Less common methods are capillary electrophoresis, microwave and fluorescence spectroscopy, nuclear magnetic resonance, and Raman optical activity. − All of the above are solution-based methods that demand a nonchiral solvent and a clear solution. In addition, upon dissolving, the chemical reaction between the solvent and the solute must be ruled out.…”

Section: Introductionmentioning

confidence: 99%

Identification of Enantiomers Using Low-Frequency Raman Spectroscopy

2022

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Distinguishing between D and L enantiomers is of important scientific interest, especially for the pharmaceutical industry. Enantiomeric differentiation in the solid form is repeatedly presented as a challenge in the research community. Raman spectroscopy is a nondestructive tool, widely used for the characterization of different materials by probing their vibrational modes. The low-frequency region of the Raman spectrum reveals lattice-level interactions and global fluctuations in the molecule. Lower frequencies correspond to vibrations arising from weaker bonds and long-range interactions and hence are very susceptible to polarization changes. This work presents low-frequency Raman (LFR) spectroscopy as a facile technique to identify enantiomers. The optical setup of conventional Raman spectroscopy is engineered such that the excitation and collection geometries use an asymmetrical focal cone. In addition, a half-wave retarder is added to the excitation path and a Glan−Taylor polarizer is added to the collection path, and these modifications allow us to select the polarization plane for both excitation and collection geometries. The asymmetry in the foci when using a polarized beam for excitation provides different intensities of the collected signal for each polarization plane. In a calibrated system, one can define the chirality of an analyte by comparing the intensity of the LFR signal along orthogonal sets of polarization planes. For nonchiral molecules, the spectral intensity is always higher in the co-polarized plane when compared to the orthogonally depolarized plane, as expected. This contrast in the intensity of Raman spectra serves as a distinct tool for identifying enantiomers.

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Enantiomeric characterization and structure elucidation of Otamixaban

Cited by 6 publications

References 17 publications

Current and Emerging Direct Oral Anticoagulants: State-of-the-Art

Current and Emerging Direct Oral Anticoagulants: State-of-the-Art

Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy

Identification of Enantiomers Using Low-Frequency Raman Spectroscopy

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