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Late Stage Fluorination and its Applications to Drug Discovery

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Deliverables

Batch to Flow for best catalytic fluorinations

The late stage fluorination methodology developed in batch by ESRs 1-2 will be extended to continuous-flow chemistry to improve the reaction conditions and facilitae the scale-up of fragments and leads from mg to g and kg scale.

Supervisory Board of the Network

Effective nomination of the Supervisory Board of FLUDD

Website and Newsletters

Website and Newsletters regularly updated and sustained including partner websites

Synthesis of 18F-radioligands to image enzyme GPCR and kinase targets (Neuro)

Selection of labeled 18F-molecules for the production of 18F-radioligands to image enzyme and GPCR targets within the Janssen Neuroscience portfolio. IMAp will be involved in the design of radioligands to support JANSSEN CNS drug discovery programs involving ESR3.

Synthesis of 18F-carbohydrate probe for TB

NIH and UOXFd have demonstrated that Mycobacterium tuberculosis (Mtb, the causative agent of TB) is specifically ‘labeled’ by trehalose-based probes in a manner that is dependent on an enzymatic mechanism unique to TB.

Catalytic fluorination via CH functionalization of cyclobutanes, bicycles, spirocycles, oxetanes, thietanes and azetidines

ESR1 will examine the subtle geometric, steric, and electronic effects at play in auxiliary guided C−H fluorination of cyclobutanes, oxetanes, thietanes and azetidines.

Production of TB 18F-probe under GMP conditions

Mycobacterium tuberculosis (Mtb, the causative agent of TB) is specifically ‘labeled’ by trehalose-based probes. ESR5 will work on a scalable enzymatic process free of endotoxins at a GMP standard.

Patents, research and review publications, assistance for creation of start-ups and incubation

Patents, research and review publications, assistance for creation of start-ups and incubation, help to the writing of research projects.

(Pre)clinical evaluation of TB 18F-probe

The progression of the TB probe developed by ESR5 to (pre)clinical evaluation will be orchestrated under WP3.

Metabolic studies and preclinical evaluation of priority 19/18F-molecules

OXF and JAN will generate a number of novel 19F- and 18F-fluorinated fragments and molecules, for which metabolic stability is unclear or unknown, and will require systematic investigation. All ESRs will be involved.

18F-Labeling of cyclobutanes, bicycles, spirocycles, oxetanes, thietanes, azetidines, thiazines and thiazoles

Novel methods developed by ESRs 1-2 will provide a range of novel 18F-molecules that will be tested for metabolic stability and preclinical evaluation (WP3).

Dissemination of main results throughout the consortium and outside (oral and poster presentations) (eg International conferences)

Dissemination of main results throughout the consortium and outside (oral and poster presentations).

Methods based on [18F][:CF2] carbene radiochemistry to label 18F-arylOCHF2 and 18F-arylSCHF2

The radiosynthesis of 18F-arylOCHF2 will be envisaged by OH insertion of directly available (hetero)arylOH with the in situ prepared 18F-labeled carbene [18F][:CF2].

Catalytic fluorocyclization of alkenes and alkynes towards thiazoles and thiazines

ESR2 - Fluorination will be extended to alkenes as illustrated with the construction of fluorine-containing thiazoles and thiazines.

Metabolic studies and preclinical evaluation of priority 19/18F-biomolecules

UOXF and JANb will generate a number of novel 19F- and 18F-fluorinated fragments and biomolecules, for which metabolic stability is unclear or unknown, and will require systematic investigation. All ESRs will be involved.

Site selective 18F-Labeling of proteins eg AnnexinV, MCP1/CCL5, BACE1, GSM, APP, Tau

ESR4 will collaborate with JANb to the development and translation of new reactions to jointly selected protein systems such as Annexin V, proleukin (IL-2), MCP1/CCL5, icosahedral virus-capsid proteins and fluoro-mAbs/ADCs.

Methods based on CH functionalization to 18F-label new 18F-chemotypes (eg (hetero)arylCHF2)

ESR3 will develop novel 18F-labeling methods towards, at first instance, (hetero)arylCHF2 and (hetero)arylOCHF2 in high specific activity.

Selection and synthesis of best fragment- lead candidates for medicinal chemistry

ESR1 and ESR2 will develop innovative methodology based on Csp3-H and alkene functionalization to access new fluorine-containing motifs, bioisosteres and molecules for applications in medicinal chemistry.

Methods for site selective 18F-labeling of proteins

New C–C and C–F bond forming methods under development by OXFd will allow the first exploration of this new form of protein mutagenesis, allowing the power of the F atom to be fully applied to control biology.

Defense of DPhil Thesis (Oxford)

Redaction and defense of Thesis for the awarding of the doctoral degree (Oxford).

FLUDD Schools

Formal annual FLUDD school with taught training component oral communications by all ESRs and plenary lecturers

Public Website, Press release, Outreach, Open days, Embassy

Public website design and maintenance including press release outreach activities open days embassy

ESR recruitment process

Effective recruitment of all ESRs according to the priniciple of transparency and non-discrimination

Improvement of employability

Improvement of employability through training in job search, career paths, management & entrepreneurship.

Workshops and (inter)national conferences

Monitoring the atendance of all ESRs to network-wide workshops and to external workshops and (inter)national conferences.

Publications

Easy Access to Aliphatic Sulfonamides using Sulfamoyl Chlorides Under Visible Light Activation

Author(s): Sandrine M. Hell, Claudio F. Meyer, Andrés A. Trabanco, Véronique Gouverneur
Published in: Journal of Visualized Experiments, Issue 161, 2020, ISSN 1940-087X
Publisher: MYJoVE Corporation
DOI: 10.3791/61384

Light-driven post-translational installation of reactive protein side chains

Author(s): B. Josephson, C. Fehl, P. G. Isenegger, S. Nadal, T. H. Wright, A. W. J. Poh, B. J. Bower, A. M. Giltrap, L. Chen, C. Batchelor-McAuley, G. Roper, O. Arisa, J. B. I. Sap, A. Kawamura, A. J. Baldwin, S. Mohammed, R. G. Compton, V. Gouverneur, B. G. Davis
Published in: Nature, Issue 585, 2020, Page(s) 530-537, ISSN 0028-0836
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-020-2733-7

Hydrodifluoromethylation of Alkenes with Difluoroacetic Acid

Author(s): Claudio F. Meyer, Sandrine M. Hell, Antonio Misale, Andres A Trabanco, Veronique Gouverneur
Published in: Angewandte Chemie International Edition, 2019, ISSN 1433-7851
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/anie.201903801

Hydrochlorofluoromethylation of unactivated alkenes with chlorofluoroacetic acid

Author(s): Claudio F. Meyer, Sandrine M. Hell, Jeroen B.I. Sap, Antonio Misale, Aldo Peschiulli, Daniel Oehlrich, Andrés A. Trabanco, Véronique Gouverneur
Published in: Tetrahedron, Issue 8 October 2019, 2019, Page(s) 130679, ISSN 0040-4020
Publisher: Pergamon Press Ltd.
DOI: 10.1016/j.tet.2019.130679

Silyl Radical-Mediated Activation of Sulfamoyl Chlorides Enables Direct Access to Aliphatic Sulfonamides from Alkenes

Author(s): Sandrine M. Hell, Claudio F. Meyer, Gabriele Laudadio, Antonio Misale, Michael C. Willis, Timothy Noël, Andrés A. Trabanco, Veronique Gouverneur
Published in: Journal of the American Chemical Society, 2019, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.9b13071

Hydrosulfonylation of Alkenes with Sulfonyl Chlorides under Visible Light Activation

Author(s): Sandrine Monique Hell, Claudio Flavio Meyer, Antonio Misale, Jeroen B. I. Sap, Kirsten K. Christensen, Michael C. Willis, Andrés A. Trabanco, Veronique Gouverneur
Published in: Angewandte Chemie International Edition, 2020, ISSN 1433-7851
Publisher: John Wiley & Sons Ltd.
DOI: 10.1002/anie.202004070

Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery

Author(s): Jeroen B. I. Sap, Natan J. W. Straathof, Thomas Knauber, Claudio F. Meyer, Maurice Médebielle, Laura Buglioni, Christophe Genicot, Andrés A. Trabanco, Timothy Noël, Christopher W. am Ende, Véronique Gouverneur
Published in: Journal of the American Chemical Society, Issue 142/20, 2020, Page(s) 9181-9187, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.0c03881

Hydrogen Bonding Phase-Transfer Catalysis with Ionic Reactants: Enantioselective Synthesis of γ-Fluoroamines

Author(s): Giulia Roagna, David M. H. Ascough, Francesco Ibba, Anna Chiara Vicini, Alberto Fontana, Kirsten E. Christensen, Aldo Peschiulli, Daniel Oehlrich, Antonio Misale, Andrés A. Trabanco, Robert S. Paton, Gabriele Pupo, Veronique Gouverneur
Published in: Journal of the American Chemical Society, 2020, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.0c05131

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