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Your search keyword '"Thomas Cailly"' showing total 17 results
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17 results on '"Thomas Cailly"'

1. Controlled Access to C 1 ‐Symmetrical Cyclotriveratrylenes (CTVs) by Using a Sequential Barluenga Boronic Coupling (BBC) Approach

Author

Emmanuelle Dubost, Frédéric Fabis, Clément Vigier, Thomas Cailly, Pierre Fossé, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
010405 organic chemistry, Chemistry, Supramolecular chemistry, Cyclotriveratrylene, General Chemistry, 010402 general chemistry, 01 natural sciences, Crown Compounds, 3. Good health, 0104 chemical sciences, Coupling (electronics), chemistry.chemical_compound, Computational chemistry, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021

2. Recent Advances in Synthetic Methods for Radioiodination

Author

Andrew Sutherland, Thomas Cailly, Holly McErlain, Victor Babin, Emmanuelle Dubost, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), and University of Glasgow

Subjects
Anions, 010405 organic chemistry, Chemistry, Organic Chemistry, Precursors, 010402 general chemistry, 01 natural sciences, Hydrocarbons, 0104 chemical sciences, Iodine Radioisotopes, Substitution reactions, Salts, Biochemical engineering, [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience; Organic compounds bearing radioisotopes of iodine are widely used for biological research, diagnostic imaging, and radiotherapy. Early reported synthetic methods for the incorporation of radioiodine have generally involved high temperature reactions or strongly oxidizing conditions. To overcome these limitations and to cope with the demand for novel radioiodinated probes, there has been a surge in the development of new synthetic methodology for radioiodination. This synopsis describes the key transformations developed recently.

Published
2020

3. Design of iodinated radioligands for SPECT imaging of central human 5-HT4R using a ligand lipophilicity efficiency approach

Author

Audrey Davis, Emmanuelle Dubost, Frédéric Fabis, Jean-Philippe Bouillon, Vincent Reboul, Benjamin B. Tournier, Gilbert Pigrée, Philippe Millet, Jean-François Lohier, Thomas Cailly, Victor Babin, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Geneva University Hospital (HUG), Installations de Mise en Oeuvre et de GEstion des Radioéléments [Caen] (IMOGERE), Laboratoire de chimie moléculaire et thioorganique (LCMT), Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
010405 organic chemistry, Chemistry, Organic Chemistry, 01 natural sciences, Biochemistry, Combinatorial chemistry, Serotonin SPECT imaging 5-HT4 Radio-iodination, 0104 chemical sciences, 3. Good health, ddc:616.89, 010404 medicinal & biomolecular chemistry, Lipophilic efficiency, In vivo, Spect imaging, Drug Discovery, [CHIM]Chemical Sciences, Molecular Biology, Binding affinities
Abstract

International audience; A series of iodinated ligands for the SPECT imaging of 5-HT4 receptors was designed starting from the previously reported hit MR-26132. We focused on the modulation of the piperidine-containing lateral chain by introducing hydrophilic groups in order to decrease the liphophilicity of the new ligands. All the synthesized compounds were tested for their binding affinities on 5-HT4Rs and based on the Ligand Lipophilicity Efficiency approach, compound 13 was further selected for radioiodination with iodine-125 and imaging experiments. Compound 13 showed its ability to displace the specific signal of the reference compound [125I]SB-207710 but no significant detection of [125I]13 was observed in vivo in SPECT experiments.

Published
2020

4. Improvements of C–H Radio-Iodination of N-Acylsulfonamides toward Implementation in Clinics

Author

Gilbert Pigrée, Thomas Cailly, Jean-Philippe Bouillon, Alexandra Hébert, Florian Benoist, Emmanuelle Dubost, Frédéric Fabis, Victor Babin, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Installations de Mise en Oeuvre et de GEstion des Radioéléments [Caen] (IMOGERE), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
010405 organic chemistry, Organic Chemistry, chemistry.chemical_element, Halogenation, 010402 general chemistry, palladium, 01 natural sciences, Combinatorial chemistry, Catalysis, 0104 chemical sciences, chemistry, iodination, C–H activation, radiochemistry, iodine­-125, [CHIM.RADIO]Chemical Sciences/Radiochemistry, Palladium
Abstract

International audience; An improved protocol to perform C–H radio-iodination is described. These new conditions allow rapid and clean formation of radio-iodinated N-acylsulfonamides using [125I]NIS and catalytic amounts of palladium acetate and para-toluenesulfonic acid. No pre-functionalized precursors are required and the products are obtained with radiochemical conversions (RCC) of 27–84%.

Published
2019

5. Palladium-Mediated Site-Selective C–H Radio-iodination

Author

Alain Manrique, Victor Babin, Emmanuelle Dubost, Frédéric Fabis, Céline Chollet, Jean-Philippe Bouillon, Alexandra Hébert, Thomas Cailly, Grégory Pieters, Florian Benoist, Pierre Barbey, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU), Service de Chimie Bio-Organique et de Marquage (SCBM), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Primary (chemistry), 010405 organic chemistry, Organic Chemistry, Halogenation, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Biochemistry, Medicinal chemistry, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Sodium iodide, Site selective, Physical and Theoretical Chemistry, [CHIM.RADIO]Chemical Sciences/Radiochemistry, Palladium
Abstract

International audience; The palladium-mediated C–H radio-iodination of arenes using sodium iodide as the primary isotopic source is reported and performed without chemical know-how in 30 min and applied to the synthesis of complex radio-iodinated compounds of biological interest.

Published
2018

6. Boron reagents for divergent radiochemistry

Author

Thomas C. Wilson, Véronique Gouverneur, Thomas Cailly, European Southern Observatory (ESO), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Chemistry Research Laboratory [Oxford, UK], and University of Oxford [Oxford]

Subjects
Tomography, Emission-Computed, Single-Photon, Radiochemistry, 010405 organic chemistry, chemistry.chemical_element, General Chemistry, 010402 general chemistry, 01 natural sciences, 3. Good health, 0104 chemical sciences, Human health, chemistry, Positron-Emission Tomography, Reagent, Spect imaging, Humans, Radiopharmaceuticals, Molecular imaging, Boron, [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience; Radiolabelled (bio)molecules have advanced many areas of science from fundamental biology to human health including applications in molecular imaging and more generally nuclear medicine. Today, the field of radiochemistry is rapidly expanding, a trend resulting from the increasing demand for labelled molecules necessary for diagnosis and to accelerate pharmaceutical drug development. More often, the synthesis of labelled (bio)molecules employs a pre-functionalised precursor to allow for the chemoselective installation of a particular radioisotope-containing substituent. Among the array of precursors available, boron reagents occupy a prominent place because they are easy to handle, numerous possibilities exist for their preparation, and their reactivity has been well studied especially in cross-coupling chemistry. In this review, we discuss the value of boron-based precursors for the radiolabelling of (bio)molecules with the radionuclides carbon-11, fluorine-18, iodine-123, iodine-125 and iodine-131, and we illustrate how these radiosynthetic advances have opened the radiochemical space available for areas such as PET and SPECT imaging.

Published
2018

7. Synthesis of substituted diazino[c]quinolin-5(6H)-ones, diazino[c]isoquinolin-6(5H)-ones, diazino[c]naphthyridin-6(5H)-ones and diazino[c]naphthyridin-5(6H)-ones

Author

Thomas Cailly, Jean-Philippe Bouillon, Frédéric Fabis, Nathalie Fresneau, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
[CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Organic Chemistry, Drug Discovery, Closure (topology), 010402 general chemistry, Ring (chemistry), 01 natural sciences, Biochemistry, Medicinal chemistry, 0104 chemical sciences
Abstract

International audience; Substituted diazino[c]quinolin-5(6H)-ones and -isoquinolin-6(5H)-ones, diazino[c]naphthyridin-6(5H)- and -5(6H)-ones were obtained using two synthetic routes: one-pot cross-coupling/cyclization and two-step cross-coupling/KOH-mediated anionic ring closure. The two strategies gave yields in the same order of magnitude and their choice depends on the availability of the starting material.

Published
2013

8. Iodoindazoles with Selective Magnesiation at Position 3: A Route to Highly Functionalized Indazoles

Author

Frédéric Fabis, Yohann Berhault, Thomas Cailly, Silvia Stiebing, Bao Vy Lam, Valérie Collot, Christine Fossey, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
heterocycles, 010405 organic chemistry, Metalation, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Regioselectivity, General Chemistry, metalation, magnesium, 010402 general chemistry, 01 natural sciences, Catalysis, 3. Good health, 0104 chemical sciences, regioselectivity, Electrophile, Halogen, synthetic methods, Organic chemistry
Abstract

International audience; A unique route to highly functionalized indazoles is described. A regioselective magnesiation at position 3 of 4-, 5-, 6- and 7-iodo-2-THP-indazoles (THP=tetrahydropyranyl) has been developed using TMPMgCl⋅LiCl (TMP=2,2,6,6-tetramethylpiperidyl). The obtained magnesiate can be trapped by different electrophiles to introduce a wide range of functional groups including halogens, thioalkyls, alcohols, aldehydes, ketones, amides, or esters at position 3. Once this position is functionalized, the iodine atoms can be further reacted through metal-halogen exchange or cross-coupling strategies. Finally, N-substitution reactions allow the synthesis of a variety of highly functionalized indazoles giving access to these valuable scaffolds through a simple and unique route

Published
2016

9. Radiosynthesis of SPECT tracers via a copper mediated 123 I iodination of (hetero)aryl boron reagents

Author

Thomas Cailly, Véronique Gouverneur, Sean Preshlock, Matthew Tredwell, Greg McSweeney, Thomas C. Wilson, Stefan Verhoog, European Southern Observatory (ESO), Chemistry Research Laboratory [Oxford, UK], University of Oxford [Oxford], Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Copper mediated, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Catalysis, chemistry.chemical_compound, Nucleophile, Materials Chemistry, Organic chemistry, Boron, 010405 organic chemistry, Aryl, Radiosynthesis, Metals and Alloys, Halogenation, Substrate (chemistry), General Chemistry, Combinatorial chemistry, 3. Good health, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, chemistry, Reagent, Ceramics and Composites, [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience; A general method for the copper mediated nucleophilic 123I-iodination of (hetero)aryl boronic esters and acids has been developed. The broad substrate scope of this radiosynthetic approach allows access to [123I]DPA-713, [123I]IMPY, [123I]MIBG and [123I]IPEB that are four commonly used SPECT radiotracers. Our results infer that aryl boronic reagents can now be employed as common precursors for both fluorine-18 and iodine-123 radiolabelling.

Published
2016

10. Enhanced copper-mediated 18 F-fluorination of aryl boronic esters provides eight radiotracers for PET applications

Author

Thomas Cailly, Alexander Hoepping, Véronique Gouverneur, Thomas C. Wilson, Jan Mollitor, Samuel Calderwood, Joël Mercier, Thomas Lee Collier, Michael Schedler, Mickael Huiban, Stefan Gruber, Marco Mueller, René Smits, Nicholas J. Taylor, Stefan Verhoog, Matthew Tredwell, Sean Preshlock, Christophe Genicot, Jan Passchier, Antje Hienzsch, Chemistry Research Laboratory [Oxford, UK], University of Oxford [Oxford], Hammersmith Hospital NHS Imperial College Healthcare, ABX advanced biochemical compounds GmbH (ABX GmbH), European Southern Observatory (ESO), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Organisch-Chemisches Institut der Westfälischen Wilhelms-Universität Münster, Westfälische Wilhelms-Universität Münster (WWU), ADVION, Erasmus University Medical Center [Rotterdam] (Erasmus MC), and UCB Pharma S.A.[Braine-l'Alleud]

Subjects
Fluorine Radioisotopes, Halogenation, Copper mediated, 010402 general chemistry, 01 natural sciences, Medicinal chemistry, Catalysis, chemistry.chemical_compound, Materials Chemistry, Organic chemistry, Radioactive Tracers, 010405 organic chemistry, Aryl, Metals and Alloys, Esters, General Chemistry, Boronic Acids, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, chemistry, Positron-Emission Tomography, Ceramics and Composites, [CHIM.RADIO]Chemical Sciences/Radiochemistry, Copper
Abstract

International audience; [18F]FMTEB, [18F]FPEB, [18F]flumazenil, [18F]DAA1106, [18F]MFBG, [18F]FDOPA, [18F]FMT and [18F]FDA are prepared from the corresponding arylboronic esters and [18F]KF/K222 in the presence of Cu(OTf)2py4. The method was successfully applied using three radiosynthetic platforms, and up to 26 GBq of non-carrier added starting activity of 18F-fluoride.

Published
2016

11. Synthesis and structure-affinity relationships of selective high-affinity 5-HT(4) receptor antagonists: application to the design of new potential single photon emission computed tomography tracers

Author

Fabienne Dulin, Noé Dumas, Céline Ballandonne, Christine Fossey, Thomas Cailly, Emmanuelle Dubost, Frédéric Fabis, Rosa Magnelli, Jana Sopkova de-Oliveira Santos, Sabrina Butt-Gueulle, Philippe Millet, Yves Charnay, Sylvain Rault, Daniel H. Caignard, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Embedded System Lab (ESL), Thales Research and Technology, and Hôpitaux Universitaires de Genève (HUG)

Subjects
Serotonin 5-HT4 Receptor Antagonists, Piperidines/pharmacology, Stereochemistry, chemistry.chemical_element, Serotonin 5-HT4 Receptor Antagonists/chemical synthesis/pharmacology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ligands, 010402 general chemistry, 01 natural sciences, Article, Dioxanes, Iodine Radioisotopes, Mice, Radioligand Assay, Structure-Activity Relationship, chemistry.chemical_compound, Piperidines, In vivo, Drug Discovery, medicine, Animals, Humans, Receptor, 5-HT receptor, Tomography, Emission-Computed, Single-Photon, Phenanthridine, medicine.diagnostic_test, Dioxanes/pharmacology, 010405 organic chemistry, Antagonist, 0104 chemical sciences, chemistry, Drug Design, Molecular Probes, Fluorine, Molecular Medicine, Receptors, Serotonin, 5-HT4, Receptors, Serotonin, 5-HT4/chemistry/metabolism, Radiopharmaceuticals, Selectivity, Emission computed tomography
Abstract

The work described herein aims at finding new potential ligands for the brain imaging of 5-HT(4) receptors (5-HT(4)Rs) using single-photon emission computed tomography (SPECT). Starting from the nonsubstituted phenanthridine compound 4a, exhibiting a K(i) value of 51 nM on the 5-HT(4)R, we explored the structure-affinity in this series. We found that substitution in position 4 of the tricycle with a fluorine atom gave the best result. Introduction of an additional nitrogen atom inside the tricyclic framework led to an increase of both the affinity and selectivity for 5-HT(4)R, suggesting the design of the antagonist 4v, exhibiting a high affinity of 0.04 nM. Several iodinated analogues were then synthesized as potential SPECT tracers. The iodinated compound 11d was able to displace the reference radioiodinated 5-HT(4)R antagonist (1-butylpiperidin-4-yl)methyl-8-amino-7-iodo[(123)I]-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate {[(123)I]1, [(123)I]SB 207710} both in vitro and in vivo in brain. Compound 11d was radiolabeled with [(125)I]iodine, providing a potential SPECT candidate for brain imaging of 5-HT(4)R.

Published
2012
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12. A general synthesis of diversely substituted indazoles and hetero-aromatic derivatives from O-halo-(het)arylaldehydes or -phenones

Author

Emmanuelle Dubost, Frédéric Fabis, Thibault Ferrary, Valérie Collot, Thomas Cailly, Silvia Stiebing, Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Indazole, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Organic Chemistry, chemistry.chemical_element, Heterocycles, 010402 general chemistry, 01 natural sciences, Biochemistry, Combinatorial chemistry, [ CHIM ] Chemical Sciences, 0104 chemical sciences, Catalysis, chemistry.chemical_compound, CyclizationIndazole, Drug Discovery, Cross-coupling, Palladium, Amination, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; A set of variously substituted indazoles and hetero-aromatic derivatives were synthesized from o-halo-(het)arylaldehydes using a palladium catalyzed amination followed by cyclization. Starting from phenones, this process was extended to give 3-substituted indazoles. Moreover, N-1-substituted-indazoles can be reached by this strategy using an optional selective N-1-alkylation step during the process. This methodology offers a general and easy route for the synthesis of regioselectively substituted indazoles.

Published
2014

13. Design of fluorinated 5-HT4R antagonists: Influence of the basicity and lipophilicity toward the 5-HT4R binding affinities

Author

Bruno Linclau, Frédéric Fabis, Zhong Wang, Thomas Cailly, Clement Q. Fontenelle, Christine Fossey, Lesnard, Aurélien, School of Chemistry, University of Southampton [Southampton], Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), School of Chemistry [Southampton, UK], University of Southampton, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Serotonin 5-HT4 Receptor Antagonists, Halogenation, Stereochemistry, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Clinical Biochemistry, Guinea Pigs, Pharmaceutical Science, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 01 natural sciences, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Piperidines, Drug Discovery, Animals, Humans, Receptor, Molecular Biology, 5-HT receptor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Binding affinities, 0303 health sciences, 010405 organic chemistry, Chemistry, Organic Chemistry, [ CHIM.THER ] Chemical Sciences/Medicinal Chemistry, 0104 chemical sciences, 3. Good health, Nitrogen atom, Drug Design, Lipophilicity, Molecular Medicine, Piperidine, Receptors, Serotonin, 5-HT4, Selectivity
Abstract

Analogues of potent 5-HT(4)R antagonists possessing a fluorinated N-alkyl chain have been synthesized in order to investigate the effect of the resulting change in basicity and lipophilicity on the affinity and selectivity profile. We demonstrate that for this series, the affinity is decreased with decreased basicity of the piperidine's nitrogen atom. In contrast, the resulting increase in lipophilicity has minimal impact on binding affinity and selectivity. 3,3,3-Trifluoropropyl and 4,4,4-trifluorobutyl derivatives 6d and 6e have shown to bind to the 5-HT(4)R while maintaining their pharmacological profile and selectivity toward other 5-HT receptors.

Published
2013

14. N-tosylcarboxamide as a transformable directing group for Pd-catalyzed C-H ortho-arylation

Author

Thomas Cailly, Christine Fossey, Frédéric Fabis, Florent Peron, Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Stereochemistry, Carboxylic Acids, 010402 general chemistry, 01 natural sciences, Biochemistry, Catalysis, Addition reactions, Tosyl Compounds, Group (periodic table), Organic reactions, Physical and Theoretical Chemistry, Materials, ComputingMilieux_MISCELLANEOUS, Reaction conditions, Molecular Structure, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Arylation, Hydrocarbons, 0104 chemical sciences, Intramolecular force, Divergent synthesis, Palladium
Abstract

International audience; The N-tosylcarboxamide group offers the possibility of directing the Pd-catalyzed C–H arylation of arenes providing a new entry to biarylcarboxamides. Moreover, its ability to react according to different reaction conditions including intramolecular reactions makes it a pivotal directing group for a divergent synthesis of biaryl-based compounds

Published
2012

15. One-pot synthesis of new aza- and diaza-aminopenanthrenes

Author

Patrick Dallemagne, Thomas Cailly, Rodrigue Yougnia, Christophe Rochais, Jana Sopkova‐de Oliveira Santos, Sylvain Rault, Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Phenanthroline, Fused ring system, One-pot synthesis, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Azaphenanthrene, 010402 general chemistry, Ring (chemistry), Dieckmann–Thorpe, 01 natural sciences, Biochemistry, Chemical synthesis, Benzoquinoline, chemistry.chemical_compound, Suzuki–Miyaura cross-coupling, Drug Discovery, Organic chemistry, Ring closure, ComputingMilieux_MISCELLANEOUS, 010405 organic chemistry, Chemistry, Organic Chemistry, Quinoline, [ CHIM.THER ] Chemical Sciences/Medicinal Chemistry, Combinatorial chemistry, 0104 chemical sciences, One pot reaction, Microwave irradiation
Abstract

International audience; The synthesis of a series of benzo(iso)quinoline and phenanthroline derivatives has been achieved using an efficient one-pot procedure. It proceeds through a Suzuki–Miyaura cross-coupling followed by a Dieckmann–Thorpe ring closure under microwave irradiation and provides easy access to building blocks not readily available through other methods

Published
2011

16. General method for the synthesis of substituted phenanthridin-6(5H)-ones using a KOH-mediated anionic ring closure as the key step

Author

Thomas Cailly, Emmanuelle Dubost, Frédéric Fabis, Rosa Magnelli, Sylvain Rault, Rémi Legay, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), and Cailly, Thomas

Subjects
Potassium hydroxide, General method, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Closure (topology), [CHIM.ORGA] Chemical Sciences/Organic chemistry, 010402 general chemistry, Ring (chemistry), 01 natural sciences, Biochemistry, Medicinal chemistry, Chemical synthesis, 0104 chemical sciences, chemistry.chemical_compound, Suzuki reaction, Drug Discovery, ComputingMilieux_MISCELLANEOUS
Abstract

Substituted phenanthridin-6(5H)-ones were obtained in a two-step procedure involving a Suzuki cross-coupling reaction followed by a KOH-mediated anionic ring closure. The influence of the nature and the position of the substituents on the cyclization step were studied. This methodology offers a general and practical route to diversely substituted phenanthridin-6(5H)-ones.

Published
2010

17. Two-step synthesis of substituted 3-aminoindazoles from 2-bromobenzonitriles

Author

Frédéric Fabis, Sylvain Rault, Valerie Lefebvre, Thomas Cailly, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
chemistry.chemical_classification, Indazoles, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Hydrazine, Two step, Hydrazone, 010402 general chemistry, 01 natural sciences, Combinatorial chemistry, 0104 chemical sciences, chemistry.chemical_compound, Benzophenones, Cyclization, Nitriles, Benzophenone, Sequence (medicine)
Abstract

International audience; A general two-step synthesis of substituted 3-aminoindazoles from 2-bromobenzonitriles involving a palladium-catalyzed arylation of benzophenone hydrazone followed by an acidic deprotection/cyclization sequence is described. This procedure offers a general and efficient alternative to the typical SNAr reaction of hydrazine with o-fluorobenzonitriles.

Published
2010

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