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Papers by Philippe Belmont
New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine p... more New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine phosphorylase (TP). Inspired by the pharmacophoric pyrimidinedione core of the natural substrate, four series have been designed in order to interact with large empty pockets of the active site: pyrimidoquinoline-2,4-diones (series A), pyrimidinedione linked to a pyrroloquinoline-1,3-diones (series B and C), the polycyclic heterocycle has been replaced by a pyrimidopyridopyrrolidinetetraone (series D). In each series, the tricyclic nitrogen heterocyclic moiety has been synthesised by a one-pot multicomponent reaction. Compared to 7-DX used as control, 2d, 2l, 2p (series A), 28a (series D), and the open intermediate 30 showed modest to good activities. A kinetic study confirmed that the most active compounds 2d, 2p are competitive inhibitors. Molecular docking analysis confirmed the interaction of these new compounds at the active binding site of TP and highlighted a plausible specific interaction in a pocket that had not yet been explored.
Chemical Communications
N-containing heterocycles are important scaffolds due to their ubiquitous presence in bioactive c... more N-containing heterocycles are important scaffolds due to their ubiquitous presence in bioactive compounds. Their synthesis has been considered as an important research field. In this work we report the access...
Organic & Biomolecular Chemistry, 2021
A combination of AcOH and Ag catalyst induced an efficient tandem reaction to form 1,2-dihydroiso... more A combination of AcOH and Ag catalyst induced an efficient tandem reaction to form 1,2-dihydroisoquinoline derivatives. Highly functionalized multiheterocyclic scaffolds are accessible straightforwardly using readily available starting materials.
The Journal of Organic Chemistry, 2021
Rearrangement reactions in organic chemistry are attractive strategies to build efficiently compl... more Rearrangement reactions in organic chemistry are attractive strategies to build efficiently complex scaffolds, in just one step, from simple starting materials. Among them, aryl migrations are certainly one of the most useful and straightforward rearrangement for building attractive carbon-carbon bonds. Of note, anionic aryl migration reactions have been largely described compared to their radical counterparts. Recently, visible-light catalysis has proven its efficiency to generate such radical rearrangements due to the concomitant loss of a particle (often CO2 or SO2), which is the driving-force of the reaction. Here, we disclose a Smiles-type rearrangement, triggered by a phosphorus-containing unit (arylphosphoramidate), therefore called "phospho-Smiles" rearrangement, allowing a Csp2-Csp2 bond formation thanks to a 1,4-aryl migration reaction. In addition, combining this approach with a radical hydroamination/amination reaction produces an amination/phospho-Smiles cascade particularly attractive, for instance, to investigate the synthesis of the phthalazine core, a scarcely described scaffold of interest for medicinal chemistry projects.
Organic letters, Jan 5, 2014
A Ag-catalyzed versatile and efficient access to 1H,1-arylisochromenes is reported. Starting from... more A Ag-catalyzed versatile and efficient access to 1H,1-arylisochromenes is reported. Starting from ortho-alkynylbenzaldehydes bearing various substitution patterns on the benzaldehyde and alkynyl units, the use of silver triflate (10 mol %) allowed a domino hydroarylation/cycloisomerization reaction process, leading to aryl-functionalized 1H-isochromene (>10 compounds, 80-98% yields). Notably, the reaction conditions were also compatible with benzaldehydes bearing an aliphatic-substituted alkynyl moiety with modest to good yields (34-88%, 10 compounds).
Tetrahedron Letters, 2004
Acridine derivatives Acridine derivatives R 0430 New Methodology for Acridine Synthesis Using a R... more Acridine derivatives Acridine derivatives R 0430 New Methodology for Acridine Synthesis Using a Rhodium-Catalyzed Benzannulation.-A novel strategy for the synthesis of 1,3-disubstituted and 1,3,7-trisubstituted acridines (VI) involves the Rh-catalyzed benzannulation of alkynylquinolines (V) as the key step.-(BELMONT*,
New Journal of Chemistry, 2006
Chemical Communications, 2011
General procedure for the AgOTf-catalyzed cyclization/acetalization tandem reaction. Silver trifl... more General procedure for the AgOTf-catalyzed cyclization/acetalization tandem reaction. Silver triflate (5 mol%) was added in one portion to a solution of 2-alkynyl-3carbaldehyde quinoline (0.1 mmol) in N,N-diethylaminoethanol (2 mL, 0.05M) under argon. The mixture was stirred at r.t. until completion of the reaction (TLC monitoring) and filtered through celite. The celite pad was abundantly washed with dichloromethane (20 mL) and the filtrate was washed with sat. aq. solution of NaHCO 3 (×3) and brine. The organic layer was then dried over Na 2 SO 4 , filtered and concentrated under reduced pressure. Flash chromatography on silica gel (c-Hexane / EtOAc (1%Et 3 N); 9 : 1 to 0 : 1) afforded the desired furoquinoline. General procedure for the Ag 2 O-catalyzed cyclization/acetalization tandem reaction.
Anti-Cancer Agents in Medicinal Chemistry, 2007
Acridine derivatives are interesting chemotherapeutic agents that were first used as antibacteria... more Acridine derivatives are interesting chemotherapeutic agents that were first used as antibacterial and antiparasite agents. In this review we wish to concentrate our attention on the anticancer properties of acridines used in clinics since the 1970s. Based on recent results, an outlook on antitumour acridine chemotherapy will be proposed. The biological activity of acridines is mainly attributed to the planarity of these aromatic structures, which can intercalate within the double-stranded DNA structure, thus interfering with the cellular machinery. Recent understanding of the mode of action of acridines leads to continuous and exciting research in this heterocyclic family. Indeed, biological targets such as topoisomerases I and II, telomerase/telomere and protein kinases emerge and allow the design of novel acridine-based patterns. This review further pinpoints the latest progress in the development of anticancer agents based on naturally occurring and synthetic acridines (e.g. acr...
Advanced Synthesis & Catalysis
European Journal of Organic Chemistry
The Journal of Organic Chemistry
Angewandte Chemie International Edition
The hippocampus also has a brood pouch to raise its babies-in a similar way the ligand protects t... more The hippocampus also has a brood pouch to raise its babies-in a similar way the ligand protects the gold center.
ChemInform
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine p... more New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine phosphorylase (TP). Inspired by the pharmacophoric pyrimidinedione core of the natural substrate, four series have been designed in order to interact with large empty pockets of the active site: pyrimidoquinoline-2,4-diones (series A), pyrimidinedione linked to a pyrroloquinoline-1,3-diones (series B and C), the polycyclic heterocycle has been replaced by a pyrimidopyridopyrrolidinetetraone (series D). In each series, the tricyclic nitrogen heterocyclic moiety has been synthesised by a one-pot multicomponent reaction. Compared to 7-DX used as control, 2d, 2l, 2p (series A), 28a (series D), and the open intermediate 30 showed modest to good activities. A kinetic study confirmed that the most active compounds 2d, 2p are competitive inhibitors. Molecular docking analysis confirmed the interaction of these new compounds at the active binding site of TP and highlighted a plausible specific interaction in a pocket that had not yet been explored.
Chemical Communications
N-containing heterocycles are important scaffolds due to their ubiquitous presence in bioactive c... more N-containing heterocycles are important scaffolds due to their ubiquitous presence in bioactive compounds. Their synthesis has been considered as an important research field. In this work we report the access...
Organic & Biomolecular Chemistry, 2021
A combination of AcOH and Ag catalyst induced an efficient tandem reaction to form 1,2-dihydroiso... more A combination of AcOH and Ag catalyst induced an efficient tandem reaction to form 1,2-dihydroisoquinoline derivatives. Highly functionalized multiheterocyclic scaffolds are accessible straightforwardly using readily available starting materials.
The Journal of Organic Chemistry, 2021
Rearrangement reactions in organic chemistry are attractive strategies to build efficiently compl... more Rearrangement reactions in organic chemistry are attractive strategies to build efficiently complex scaffolds, in just one step, from simple starting materials. Among them, aryl migrations are certainly one of the most useful and straightforward rearrangement for building attractive carbon-carbon bonds. Of note, anionic aryl migration reactions have been largely described compared to their radical counterparts. Recently, visible-light catalysis has proven its efficiency to generate such radical rearrangements due to the concomitant loss of a particle (often CO2 or SO2), which is the driving-force of the reaction. Here, we disclose a Smiles-type rearrangement, triggered by a phosphorus-containing unit (arylphosphoramidate), therefore called "phospho-Smiles" rearrangement, allowing a Csp2-Csp2 bond formation thanks to a 1,4-aryl migration reaction. In addition, combining this approach with a radical hydroamination/amination reaction produces an amination/phospho-Smiles cascade particularly attractive, for instance, to investigate the synthesis of the phthalazine core, a scarcely described scaffold of interest for medicinal chemistry projects.
Organic letters, Jan 5, 2014
A Ag-catalyzed versatile and efficient access to 1H,1-arylisochromenes is reported. Starting from... more A Ag-catalyzed versatile and efficient access to 1H,1-arylisochromenes is reported. Starting from ortho-alkynylbenzaldehydes bearing various substitution patterns on the benzaldehyde and alkynyl units, the use of silver triflate (10 mol %) allowed a domino hydroarylation/cycloisomerization reaction process, leading to aryl-functionalized 1H-isochromene (>10 compounds, 80-98% yields). Notably, the reaction conditions were also compatible with benzaldehydes bearing an aliphatic-substituted alkynyl moiety with modest to good yields (34-88%, 10 compounds).
Tetrahedron Letters, 2004
Acridine derivatives Acridine derivatives R 0430 New Methodology for Acridine Synthesis Using a R... more Acridine derivatives Acridine derivatives R 0430 New Methodology for Acridine Synthesis Using a Rhodium-Catalyzed Benzannulation.-A novel strategy for the synthesis of 1,3-disubstituted and 1,3,7-trisubstituted acridines (VI) involves the Rh-catalyzed benzannulation of alkynylquinolines (V) as the key step.-(BELMONT*,
New Journal of Chemistry, 2006
Chemical Communications, 2011
General procedure for the AgOTf-catalyzed cyclization/acetalization tandem reaction. Silver trifl... more General procedure for the AgOTf-catalyzed cyclization/acetalization tandem reaction. Silver triflate (5 mol%) was added in one portion to a solution of 2-alkynyl-3carbaldehyde quinoline (0.1 mmol) in N,N-diethylaminoethanol (2 mL, 0.05M) under argon. The mixture was stirred at r.t. until completion of the reaction (TLC monitoring) and filtered through celite. The celite pad was abundantly washed with dichloromethane (20 mL) and the filtrate was washed with sat. aq. solution of NaHCO 3 (×3) and brine. The organic layer was then dried over Na 2 SO 4 , filtered and concentrated under reduced pressure. Flash chromatography on silica gel (c-Hexane / EtOAc (1%Et 3 N); 9 : 1 to 0 : 1) afforded the desired furoquinoline. General procedure for the Ag 2 O-catalyzed cyclization/acetalization tandem reaction.
Anti-Cancer Agents in Medicinal Chemistry, 2007
Acridine derivatives are interesting chemotherapeutic agents that were first used as antibacteria... more Acridine derivatives are interesting chemotherapeutic agents that were first used as antibacterial and antiparasite agents. In this review we wish to concentrate our attention on the anticancer properties of acridines used in clinics since the 1970s. Based on recent results, an outlook on antitumour acridine chemotherapy will be proposed. The biological activity of acridines is mainly attributed to the planarity of these aromatic structures, which can intercalate within the double-stranded DNA structure, thus interfering with the cellular machinery. Recent understanding of the mode of action of acridines leads to continuous and exciting research in this heterocyclic family. Indeed, biological targets such as topoisomerases I and II, telomerase/telomere and protein kinases emerge and allow the design of novel acridine-based patterns. This review further pinpoints the latest progress in the development of anticancer agents based on naturally occurring and synthetic acridines (e.g. acr...
Advanced Synthesis & Catalysis
European Journal of Organic Chemistry
The Journal of Organic Chemistry
Angewandte Chemie International Edition
The hippocampus also has a brood pouch to raise its babies-in a similar way the ligand protects t... more The hippocampus also has a brood pouch to raise its babies-in a similar way the ligand protects the gold center.
ChemInform
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.