The Future of (Radio)‐Labeled Compounds in Research and Development within the Life Science Industry

Derdau, Volker; Elmore, Charles S.; Hartung, Thomas; McKillican, Bruce; Mejuch, Tom; Rosenbaum, Claudia; Wiebe, Christine

doi:10.1002/anie.202306019

Cited by 9 publications

(9 citation statements)

References 163 publications

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“…Stable and radioactive isotopes play a fundamental role in life science . The insertion of a radioisotope into an organic compound generates a tracer, which can be closely tracked to unveil information, essential to establish safety profiles of pharmaceuticals and agrochemicals …”

Section: Introductionmentioning

confidence: 99%

Platform for Multiple Isotope Labeling via Carbon–Sulfur Bond Exchange

Mouhsine,

Norlöff,

Ghouilem

et al. 2024

J. Am. Chem. Soc.

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In this work, we explore a nickel-catalyzed reversible carbon−sulfur (C−S) bond activation strategy to achieve selective sulfur isotope exchange. Isotopes are at the foundation of applications in life science, such as nuclear imaging, and are essential tools for the determination of pharmacokinetic and dynamic profiles of new pharmaceuticals. However, the insertion of an isotope into an organic molecule remains challenging, and current technologies are element-specific. Despite the ubiquitous presence of sulfur in many biologically active molecules, sulfur isotope labeling is an underexplored field, and sulfur isotope exchange has been overlooked. This approach enables us to move beyond standardized element-specific procedures and was applied to multiple isotopes, including deuterium, carbon-13, sulfur-34, and radioactive carbon-14. These results provide a unique platform for multiple isotope labeling and are compatible with a wide range of substrates, including pharmaceuticals. In addition, this technology proved its potential as an isotopic encryption device for organic molecules.

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Section: Introductionmentioning

confidence: 99%

Platform for Multiple Isotope Labeling via Carbon–Sulfur Bond Exchange

Mouhsine,

Norlöff,

Ghouilem

et al. 2024

J. Am. Chem. Soc.

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“…The introduction of carbon isotopes ( 13 C and 14 C) into strategic positions of pharmaceutically active molecules is a crucial step for performing metabolic and pharmacokinetic studies (DMPK), the results of which ultimately determine their fate as potential drug candidates. 1,2 Similarly, in the search for new agrochemicals, their corresponding carbon isotopologues allow studies regarding metabolic profiling and the establishment of any possible human, soil, and groundwater contamination. [3][4][5] As such, it is imperative that efficient and accessible synthetic labelling technologies are at hand to facilitate late-stage installations of the isotope label into scaffolds of prospective drug entities.…”

Section: Introductionmentioning

confidence: 99%

Efficient palladium-catalyzed electrocarboxylation enables late-stage carbon isotope labelling

Skrydstrup,

Batista,

Ebenbauer

et al. 2024

Preprint

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Carbon isotope labelling of bioactive molecules is a critical step for accessing the pharmacokinetic and pharmacodynamic properties of new drug entities. Aryl carboxylic acids represent an important class of structural motifs commonly found in many pharmaceutically active molecules and are ideal target structures for the installation of a radioactive tag employing isotopically labelled CO2. However, direct isotope incorporation via the reported catalytic reductive carboxylation (CRC) of aryl electrophiles relies on excess CO2, which is incompatible with carbon-14 isotope incorporation. Furthermore, the application of some CRC reactions for late-stage carboxylation is limited because of the low tolerance of molecular complexity by the catalytic systems. Herein, we report the development of a practical and affordable electrochemical CRC setup based on palladium catalysis. This approach enables the use of near-stoichiometric 14CO2 generated from the primary carbon-14 source Ba14CO3, facilitating late-stage and single-step carbon-14 labelling of pharmaceuticals and representative precursors. Further studies provide more details in the mechanistic understanding of this process, allowing CRC to be performed in solvents alternative to DMF. The proposed isotope-labelling protocol holds significant promise for immediate impact on drug development programmes.

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“…Tritium-labeled compounds, serving as valuable radiotracers, play a crucial role in various stages of the drug discovery process by providing essential information about the biological fate of drug candidates. They are widely used in receptor binding, receptor occupancy, autoradiography, and the study of drug adsorption, distribution, metabolism, and excretion (ADME) . Incorporating tritium into organic molecules, especially pharmaceuticals at a late stage, has attracted considerable attention due to these myriad applications .…”

Section: Introductionmentioning

confidence: 99%

Directed Aromatic Deuteration and Tritiation of Pharmaceuticals by Heavy Alkali Metal Amide Catalysts

Du,

Li,

Christodoulou

et al. 2024

ACS Catal.

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The Future of (Radio)‐Labeled Compounds in Research and Development within the Life Science Industry

Cited by 9 publications

References 163 publications

Platform for Multiple Isotope Labeling via Carbon–Sulfur Bond Exchange

Platform for Multiple Isotope Labeling via Carbon–Sulfur Bond Exchange

Efficient palladium-catalyzed electrocarboxylation enables late-stage carbon isotope labelling

Directed Aromatic Deuteration and Tritiation of Pharmaceuticals by Heavy Alkali Metal Amide Catalysts

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