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1. Synthesis of the calcilytic ligand NPS 2143

Author

Henrik Johansson, Thomas Cailly, Alex Rojas Bie Thomsen, Hans Bräuner-Osborne, and Daniel Sejer Pedersen

Subjects
epoxides, GPCR, NPS 2143, nucleophilic aromatic substitution, pyrylium chemistry, Science, Organic chemistry, QD241-441
Abstract

(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.

Published
2013
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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. 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

7. 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

8. 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

9. 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

10. Synthesis and evaluation of novel serotonin 4 receptor radiotracers for single photon emission computed tomography

Author

Christophe Rochais, Audrey Davis, Sophie Corvaisier, Thomas Cailly, Cédric Lecoutey, Céline Ballandonne, Frédéric Fabis, Benjamin B. Tournier, Patrick Dallemagne, Philippe Millet, Marc Since, Julien Lalut, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), and Hôpitaux Universitaires de Genève (HUG)

Subjects
0301 basic medicine, Serotonin, Benzamides/chemical synthesis/chemistry, Radioligand, Analytical chemistry, Molecular imaging, 5-HT4, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Chemistry Techniques, Synthetic, Single-photon emission computed tomography, Iodine Radioisotopes, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, ddc:616.89, 0302 clinical medicine, Receptors, Serotonin, 5-HT4/metabolism, Drug Discovery, medicine, Animals, Humans, Radioactive Tracers, Receptor, Benzamide, 5-HT receptor, Pharmacology, Tomography, Emission-Computed, Single-Photon, medicine.diagnostic_test, Ligand, Chemistry, Organic Chemistry, General Medicine, Ketones, Tomography, Emission-Computed, Single-Photon/methods, Rats, 030104 developmental biology, SPECT, Lipophilicity, Benzamides, Biophysics, Receptors, Serotonin, 5-HT4, Ketones/chemical synthesis/chemistry, 030217 neurology & neurosurgery
Abstract

International audience; Despite its implication in several physiological and pathological processes the serotonin subtype-4 receptor (5-HT4R) has seen limited effort for the development of radiolabeling agent especially concerning single photon emission computed tomography (SPECT). Bearing an ester function, the available ligands are rapidly susceptible to hydrolysis which limits their use in vivo. In this study the synthesis of iodinated benzamide and ketone analogs were described. Their affinity for the 5-HT4R and their lipophilicity were evaluated and the most promising derivatives were evaluated ex vivo for their binding to the receptor and for their ability to displace the reference ligand [125I]-SB207710.

Published
2016

11. Regioselective functionalization of 2-(2′-fluorophenyl)-3-cyanopyridine and its cyclization to benzo[h]-1,6-naphthyridines

Author

Thomas Cailly and Mikael Begtrup

Subjects
Potassium hydroxide, Lithium amide, Nitrile, medicine.drug_class, Potassium, Organic Chemistry, chemistry.chemical_element, Regioselectivity, Carboxamide, Biochemistry, Medicinal chemistry, chemistry.chemical_compound, chemistry, Drug Discovery, Pyridine, medicine, Lithium
Abstract

Benzo[h]-1,6-naphthyridines and 5-ones, selectively functionalized at C-2, C-3, C-5 and C-10, were obtained by alkyllithium-, lithium amide- or potassium hydroxide-induced anionic cyclization of 3-cyano-2-(2-fluorophenyl)pyridine, which was functionalized regioselectively at positions 4, 5, 6, and 6′.

Published
2010

12. Straightforward Access to Ethyl 3-Aminofuropyridine-2-carboxylates from 1-Chloro-2-cyano- or 1-Hydroxy-2-cyano-Substituted Pyridines

Author

Thomas Cailly, Stephane Lemaitre, Frédéric Fabis, and Sylvain Rault

Subjects
Chemistry, Organic Chemistry, Structural isomer, Medicinal chemistry, Catalysis
Abstract

The conditions of the synthesis of the four regioisomers of ethyl 3-aminofuropyridine-2-carboxylate are described and discussed in detail. The starting materials are either 1-chloro-2-cyanopyridines or 1 -cyano-2-hydroxypyridines.

Published
2007

13. The synthesis of three new heterocycles: the pyrido[4,3 or 3,4 or 2,3-c]-1,5-naphthyridines

Author

Hassan Oulyadi, Thomas Cailly, Rémi Legay, Sylvain Rault, and Frédéric Fabis

Subjects
Stereochemistry, Chemistry, Organic Chemistry, Drug Discovery, Closure (topology), Halogenation, General Medicine, Ring (chemistry), Biochemistry, Medicinal chemistry
Abstract

Pyrido[4,3 or 3,4 or 2,3- c ]-1,5-naphthyridines were obtained with good yields after chlorodehydroxylation and dehalogenation reactions starting from the parent pyridonaphthyridinones. These pyridonaphthyridinones were synthesized in a two-step procedure using a Suzuki cross-coupling reaction between 2-chloro-3-fluoropyridine and orthocyanopyridylboronic esters followed by a KOH-mediated anionic ring closure.

Published
2007

14. Design of a serotonin 4 receptor radiotracer with decreased lipophilicity for single photon emission computed tomography

Author

Céline Ballandonne, Frédéric Fabis, Noé Dumas, Philippe Millet, Aurélien Lesnard, Christine Fossey, Jean-Philippe Bouillon, Benjamin B. Tournier, Yves Charnay, Nathalie Fresneau, Thomas Cailly, 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), Hôpitaux Universitaires de Genève (HUG), 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, Stereochemistry, 5-HT, Molecular imaging, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Single-photon emission computed tomography, Ligands, Iodine Radioisotopes, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, ddc:616.89, 0302 clinical medicine, In vivo, Spect imaging, Drug Discovery, medicine, Humans, 5-HT receptor, 030304 developmental biology, Pharmacology, Tomography, Emission-Computed, Single-Photon, 0303 health sciences, Phenanthridine, medicine.diagnostic_test, Dose-Response Relationship, Drug, Molecular Structure, Organic Chemistry, Brain, General Medicine, 3. Good health, Phenanthridines, chemistry, Drug Design, SPECT, Lipophilicity, Biophysics, Receptors, Serotonin, 5-HT4, Radiopharmaceuticals, 030217 neurology & neurosurgery, Radiolabeling, Iodine
Abstract

International audience; With the aim to develop a suitable radiotracer for the brain imaging of the serotonin 4 receptor subtype (5-HT4R) using single photon emission computed tomography (SPECT), we synthesized and evaluated a library of di- and triazaphenanthridines with lipophilicity values which were in the range expected to favour brain penetration, and which demonstrated specific binding to the target of interest. Adding additional nitrogen atoms to previously described phenanthridine ligands exhibiting a high unspecific binding, we were able to design a radioiodinated compound [125I]14. This compound exhibited a binding affinity value of 0.094 nM toward human 5-HT4R and a high selectivity over other serotonin receptor subtypes (5-HTR). In vivo SPECT imaging studies and competition experiments demonstrated that the decreased lipophilicity (in comparison with our previously reported compounds 4 and 5) allowed a more specific labelling of the 5-HT4R brain-containing regions.

Published
2015

15. ChemInform Abstract: A General Synthesis of Diversely Substituted Indazoles and Hetero-Aromatic Derivatives from O-Halo-(het)arylaldehydes or -phenones

Author

Thomas Cailly, Valérie Collot, Emmanuelle Dubost, Frédéric Fabis, Thibault Ferrary, and Silvia Stiebing

Subjects
chemistry, chemistry.chemical_element, Organic chemistry, General Medicine, Amination, Catalysis, Palladium
Abstract

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
2015

16. A biotin-conjugated pyridine-based isatoic anhydride, a selective room temperature RNA-acylating agent for the nucleic acid separation

Author

Frédéric Fabis, Christine Fossey, Thomas Cailly, Sylvain Ursuegui, Alain Laurent, Arnaud Burr, S. Moutin, Ali Laayoun, Rodrigue Yougnia, and Cailly, Thomas

Subjects
Pyridines, Acylation, Biotin, Real-Time Polymerase Chain Reaction, Biochemistry, Mass Spectrometry, chemistry.chemical_compound, Oxazines, Pyridine, Organic chemistry, RNA, Messenger, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, Organic Chemistry, Extraction (chemistry), Temperature, HIV, RNA, Esters, DNA, [CHIM.ORGA] Chemical Sciences/Organic chemistry, chemistry, Biotinylation, Nucleic acid, RNA, Viral, Selectivity, Linker, Chromatography, Liquid
Abstract

Isatoic anhydride derivatives, including a biotin and a disulfide linker were specifically designed for nucleic acid separation. 2'-OH selective RNA acylation, capture of biotinylated RNA adducts by streptavidin-coated magnetic beads and disulfide chemical cleavage led to isolation of highly enriched RNA samples from an initial 9/1 DNA-RNA mixture. Starting from the parent compound N-methylisatoic anhydride A which was used at 65 °C, we improved the extraction process by designing a new generation of isatoic anhydrides that are able to react under smoother conditions. Among them, a pyridine-based isatoic anhydride derivative 15f was found to be reactive at room temperature, leading to enhance the efficiency and selectivity of the extraction process by significantly reducing DNA side extraction. The extracted and purified RNAs can then be detected by RT-PCR.

Published
2015

17. Synthesis ofortho-Cyanopyridylboronic Acids and Esters toward Cyano-Functionalized Bipyridines

Author

Jana Sopkova, Sylvain Rault, Stephane Lemaitre, Olivieira de Santos, Thomas Cailly, Frédéric Fabis, and Alexandre Bouillon

Subjects
inorganic chemicals, chemistry.chemical_compound, chemistry, Organic Chemistry, Pyridine, Halide, Organic chemistry, Reactivity (chemistry)
Abstract

This work describes the synthesis of ortho-cyanopyridylboronic acids and esters. Their reactivity with pyridine halides in the Suzuki cross-coupling reaction is evaluated and shows that the cyanopyridyl boronic esters appear to be more stable than their corresponding acids. These esters allowed us to synthesize new cyanobipyridine systems.

Published
2006

18. Synthesis and biological evaluation as AChE inhibitors of new indanones and thiaindanones related to donepezil

Author

Frédéric Fabis, Thomas Cailly, Guillaume Le Flem, Jana Sopkova-de Oliveira Santos, Patrick Dallemagne, Jean-Hugues Agondanou, Elodie Lescot, Silvia Stiebing, Vincent Lisowski, A.-M. Godard, Ziad Omran, François Dauphin, Michel Boulouard, and Sylvain Rault

Subjects
Models, Molecular, medicine.drug_class, Aché, Stereochemistry, Carboxamide, Crystallography, X-Ray, Chemical synthesis, Structure-Activity Relationship, chemistry.chemical_compound, Piperidines, mental disorders, Drug Discovery, medicine, Donepezil, Pharmacology, chemistry.chemical_classification, Molecular Structure, biology, Organic Chemistry, General Medicine, Acetylcholinesterase, language.human_language, In vitro, Enzyme, chemistry, Enzyme inhibitor, Drug Design, Indans, biology.protein, language, Cholinesterase Inhibitors, medicine.drug
Abstract

Sixty-four new indanones and thiaindanones related to donepezil were synthesized and evaluated in vitro as potential AChE inhibitors. Among them, 11 derivatives were found to inhibit the enzyme in the submicromolar range; the best compound revealed its inhibitory activity with an IC 50 in the same range (0.06 μM) than the reference compound, donepezil (IC 50 = 0.02 μM).

Published
2005

19. Room-Temperature ortho -Alkoxylation and -Halogenation of N -Tosylbenzamides by Using Palladium(II)-Catalyzed CH Activation

Author

Frédéric Fabis, Thomas Cailly, Jana Sopkova‐de Oliveira Santos, Florent Peron, 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
Reaction conditions, Halogenation, Molecular Structure, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, chemistry.chemical_element, Stereoisomerism, General Chemistry, Medicinal chemistry, Catalysis, Nucleophile, Organic chemistry, Alkoxylation, Stoichiometry, Palladium
Abstract

International audience; The N‐tosylcarboxamide group can direct the room‐temperature palladium‐catalyzed CH alkoxylation and halogenation of substituted arenes in a simple and mild procedure. The room‐temperature stoichiometric cyclopalladation of N‐tosylbenzamide was first studied, and the ability of the palladacycle to react with oxidants to form CX and CO bonds under mild conditions was demonstrated. The reaction conditions were then adapted to promote room‐temperature ortho‐alkoxylations and ortho‐halogenations of N‐tosylbenzamides using palladium as catalyst. The scope and limitation of both alkoxylations and halogenations was studied and the subsequent functional transformation of the N‐tosylcarboxamide group through nucleophilic additions was evaluated. This methodology offers a simple and mild route to diversely functionalized arenes.

Published
2014

20. 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

21. Biotin-conjugated N-methylisatoic anhydride: a chemical tool for nucleic acid separation by selective 2'-hydroxyl acylation of RNA

Author

Christine Fossey, Alain Laurent, N. Chivot, S. Moutin, Frédéric Fabis, Sylvain Ursuegui, Ali Laayoun, Arnaud Burr, Thomas Cailly, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Cailly, Thomas, Centre d'Etudes et de Recherche sur le Médicament de Normandie ( CERMN ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), and Lesnard, Aurélien

Subjects
Acylation, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Biotin, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Conjugated system, Cleavage (embryo), Catalysis, Anhydrides, chemistry.chemical_compound, Materials Chemistry, Hydroxides, Organic chemistry, ortho-Aminobenzoates, ComputingMilieux_MISCELLANEOUS, Elution, Metals and Alloys, RNA, [ CHIM.THER ] Chemical Sciences/Medicinal Chemistry, General Chemistry, DNA, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, chemistry, Ceramics and Composites, Nucleic acid, RNA, Viral, Streptavidin, Linker
Abstract

An isatoic anhydride derivative conjugated to a biotin and a disulfide linker was specifically designed for the separation of nucleic acids. Starting from a DNA–RNA mixture, a selective 2′-hydroxyl acylation of RNAs followed by capture with streptavidin-coated magnetic beads and cleavage of the disulfide led to elution of RNAs.

Published
2014

22. Synthesis of the calcilytic ligand NPS 2143

Author

Hans Bräuner-Osborne, Alex R.B. Thomsen, Thomas Cailly, Henrik Johansson, and Daniel Sejer Pedersen

Subjects
NPS-2143, pyrylium chemistry, Allosteric modulator, Chemistry, Stereochemistry, Organic Chemistry, nucleophilic aromatic substitution, Ligand (biochemistry), NPS 2143, Full Research Paper, Chiral column chromatography, lcsh:QD241-441, epoxides, GPCR, lcsh:Organic chemistry, Nucleophilic aromatic substitution, Calcilytic, lcsh:Q, Enantiomer, Enantiomeric excess, lcsh:Science
Abstract

(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.

Published
2013

23. 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

24. 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

25. Selective ortho-bromination of substituted benzaldoximes using Pd-catalyzed C-H activation : Application to the synthesis of substituted 2-bromobenzaldehydes

Author

Emmanuelle Dubost, Frédéric Fabis, Sylvain Rault, Christine Fossey, Thomas Cailly, 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), Normandie Université (NU)-Normandie Université (NU), and Lesnard, Aurélien

Subjects
Halogenation, Molecular Structure, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Combinatorial chemistry, Catalysis, [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, Benzaldehydes, Molecule, Palladium, ComputingMilieux_MISCELLANEOUS
Abstract

Substituted 2-bromobenzaldehydes were synthesized from benzaldehydes using a three-step sequence involving a selective palladium-catalyzed ortho-bromination as the key step. O-Methyloxime serves as a directing group in this reaction. A rapid deprotection of substituted 2-bromobenzaldoximes afforded substituted 2-bromobenzaldehydes with good overall yields.

Published
2011

26. 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

27. Synthesis and characterization of a iodine-125-labeled pyrrolo[1,2-a]thieno[3,2-e]pyrazine and evaluation as a potential 5-HT4R SPECT tracer

Author

Philippe Millet, Thomas Cailly, Yves Charnay, Stephane Lemaitre, Frédéric Fabis, Sylvain Rault, Noé Dumas, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Hôpitaux Universitaires de Genève (HUG), Embedded System Lab (ESL), Thales Research and Technology, and Cailly, Thomas

Subjects
Tomography, Emission-Computed, Single-Photon, Magnetic Resonance Spectroscopy, Pyrazine, Stereochemistry, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, chemistry.chemical_element, Thiophenes, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Iodine, Chemical synthesis, Iodine Radioisotopes/*chemistry/*diagnostic use, Iodine Radioisotopes, 03 medical and health sciences, chemistry.chemical_compound, ddc:616.89, 0302 clinical medicine, Drug Discovery, Pyrroles, Receptor, Pyrazines/*chemical synthesis/*diagnostic use, 5-HT receptor, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, 0303 health sciences, Organic Chemistry, Radiochemistry, General Medicine, Pyrroles/*chemical synthesis/*diagnostic use, Ligand (biochemistry), Thiophenes/*chemical synthesis/*diagnostic use, 3. Good health, chemistry, Pyrazines, 030217 neurology & neurosurgery, Preclinical imaging, Ex vivo
Abstract

In the aim to find new radiotracers for the in vivo imaging of 5-HT(4) receptors by ultra-high resolution quantitative SPECT, we have developed the synthesis of a radioiodinated 5-HT(4) ligand using an iododestannylation procedure. The [(125)I]-ligand was obtained in a high radiochemical yield. Preliminary autoradiographic and ex vivo studies failed to show a specific labeling of 5-HT(4) receptors.

Published
2010

28. ChemInform Abstract: 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, Rosa Magnelli, Sylvain Rault, Emmanuelle Dubost, Frédéric Fabis, and Rémi Legay

Subjects
General method, Chemistry, Closure (topology), Organic chemistry, General Medicine, Ring (chemistry), Medicinal chemistry
Abstract

The cyclization proceeds with both 2′-fluorobiphenyl-2-carbonitriles bearing electron-withdrawing and electron-donating groups.

Published
2010

29. 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

30. ChemInform Abstract: Regioselective Functionalization of 2-(2′-Fluorophenyl)-3-cyanopyridine and Its Cyclization to Benzo[h]-1,6-naphthyridines

Author

Thomas Cailly and Mikael Begtrup

Subjects
Substitution reaction, chemistry.chemical_compound, Lithium amide, Chemistry, Potassium, Pyridine, Organic chemistry, Halogenation, Regioselectivity, chemistry.chemical_element, Surface modification, General Medicine, Medicinal chemistry
Abstract

Benzo[h]-1,6-naphthyridines and 5-ones, selectively functionalized at C-2, C-3, C-5 and C-10, were obtained by alkyllithium-, lithium amide- or potassium hydroxide-induced anionic cyclization of 3-cyano-2-(2-fluorophenyl)pyridine, which was functionalized regioselectively at positions 4, 5, 6, and 6′.

Published
2010

31. 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

32. ChemInform Abstract: Straightforward Access to Ethyl 3-Aminofuropyridine-2-carboxylates from 1-Chloro-2-cyano- or 1-Hydroxy-2-cyano-Substituted Pyridines

Author

Sylvain Rault, Frédéric Fabis, Thomas Cailly, and Stephane Lemaitre

Subjects
Chemistry, Structural isomer, Organic chemistry, General Medicine
Abstract

The conditions of the synthesis of the four regioisomers of ethyl 3-aminofuropyridine-2-carboxylate are described and discussed in detail. The starting materials are either 1-chloro-2-cyanopyridines or 1 -cyano-2-hydroxypyridines.

Published
2008

33. A New, Direct, and Efficient Synthesis of Benzonaphthyridin-5-ones

Author

Thomas Cailly, Sylvain Rault, and Frédéric Fabis

Subjects
Potassium hydroxide, chemistry.chemical_compound, chemistry, Organic Chemistry, Drug Discovery, Microwave irradiation, Polymer chemistry, Closure (topology), Organic chemistry, General Medicine, Ring (chemistry), Biochemistry, Combinatorial chemistry
Abstract

Microwave-assisted Suzuki cross-coupling reaction of 2-fluorophenylboronic acid with all orthochlorocyanopyridine isomers allowed the rapid syntheses of key intermediates for anionic ring closure, which was performed using potassium hydroxide under microwave irradiation to give benzonaphthyridin-5-ones in high yields.

Published
2006

34. Synthesis of ortho-Cyanopyridylboronic Acids and Esters Toward Cyano-Functionalized Bipyridines

Author

Frédéric Fabis, Sylvain Rault, Olivieira de Santos, Stephane Lemaitre, Thomas Cailly, Alexandre Bouillon, and Jana Sopkova

Subjects
inorganic chemicals, chemistry.chemical_compound, Suzuki reaction, Chemistry, Pyridine, Organic chemistry, Halide, Reactivity (chemistry), General Medicine
Abstract

This work describes the synthesis of ortho-cyanopyridylboronic acids and esters. Their reactivity with pyridine halides in the Suzuki cross-coupling reaction is evaluated and shows that the cyanopyridyl boronic esters appear to be more stable than their corresponding acids. These esters allowed us to synthesize new cyanobipyridine systems.

Published
2006

35. Synthesis of ortho-Substituted Cyanopyridines Through Lithio Intermediate Trapping

Author

Sylvain Rault, Stephane Lemaitre, Thomas Cailly, Alexandre Bouillon, and Frédéric Fabis

Subjects
Group (periodic table), Chemistry, Organic Chemistry, Drug Discovery, Electrophile, Organic chemistry, Halogenation, Reactivity (chemistry), General Medicine, Trapping, Biochemistry, Medicinal chemistry
Abstract

Ortholithiation of 4-cyanopyridine using 2,2,6,6-tetramethylpiperidide (LiTMP) and trapping the lithio intermediate with electrophiles represents an efficient and straightforward access to ortho-substituted-4-cyanopyridines. The cyano group can be used as an ortho-directing group and allows the preparation of 3-halogeno-4-cyanopyridines. Reactivity of 2- and 3-cyanopyridines is also investigated and seems to give similar results.

Published
2005

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