Article
Chemistry, Organic
Ashly Rocha, Andre Lopes, Sofia Teixeira, M. Alice Carvalho
Summary: This study efficiently converts 3,4-dihydropyrimido[5,4-d]pyrimidines to new 4,8-disubstituted-pyrimido[5,4-d]pyrimidine derivatives by using piperidine and aldehydes in an acidic medium. The tandem reaction approach has a broad application, accommodating various aldehyde compounds, including phenyl, haloaryl, alkoxy-aryl, hydroxy-aryl, and heteroaryl aldehydes. 1H NMR experiments support the proposed reaction mechanism, which involves the formation of ionic reactive intermediates that explains the efficiency of this tandem approach.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Olena O. Pylypenko, Liudmyla K. Sviatenko, Kostyantin P. Shabelnyk, Sergiy I. Kovalenko, Sergiy I. Okovytyy
Summary: In this study, the mechanisms for the formation and hydrolysis of biologically active 2-substituted [1,2,4]triazolo[1,5-c]quinazolines were investigated using theoretical modeling. The results revealed that internal heterocyclization and Dimroth rearrangement are crucial steps in the formation and hydrolysis processes, respectively, and are catalyzed by water molecules. The influence of substituents on the activation barriers for these reactions is insignificant.
STRUCTURAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Seddigheh Sheikhi-Mohammareh, Ali Shiri, Joel Mague
Summary: A series of novel Se-containing tricyclic heterocycles have been synthesized through heteroannulation of a newly produced hydrazino derivative of selenazolo[4,5-d]pyrimidine with either orthoesters or carbon disulfide in pyridine followed by S-alkylation, providing new insight into the Dimroth rearrangement in both acidic and basic media for cyclocondensation of triazole on the selenazolopyrimidine framework leading to selenazolotriazolopyrimidines.
MOLECULAR DIVERSITY
(2022)
Article
Medicine, Research & Experimental
Rahul S. Bhansali, Malini Rammohan, Paul Lee, Anouchka P. Laurent, Qiang Wen, Praveen Suraneni, Bon Ham Yip, Yi-Chien Tsai, Silvia Jenni, Beat Bornhauser, Aurelie Siret, Corinne Fruit, Alexandra Pacheco-Benichou, Ethan Harris, Thierry Besson, Benjamin J. Thompson, Young Ah Goo, Nobuko Hijiya, Maria Vilenchik, Shai Izraeli, Jean-Pierre Bourquin, Sebastien Malinge, John D. Crispino
Summary: The study reveals that DYRK1A is overexpressed in and essential for B-ALL, with FOXO1 and STAT3 being critical substrates. Loss of DYRK1A-mediated FOXO1 and STAT3 signaling disrupts DNA damage and ROS regulation, leading to preferential cell death in leukemic B cells.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Chemistry, Physical
Alexandra Pacheco-Benichou, Eugenie Ivendengani, Ioannis K. Kostakis, Thierry Besson, Corinne Fruit
Summary: The copper-catalyzed Csp2-Csp2 bond forming reactions through C-H activation offer a useful strategy for the diversification of heterocyclic moieties. Specific phenylation of fused-pyrimidinones, including quinazolinone, has been achieved using this method, leading to the rapid access of various arylated N-containing polyheteroaromatics as potential bioactive compounds.
Article
Biochemistry & Molecular Biology
Joana F. Campos, Manon Cailler, Remi Claudel, Benjamin Prot, Thierry Besson, Sabine Berteina-Raboin
Summary: This study demonstrates the efficiency of three solvents, eucalyptol, cyclopentyl methyl ether, and 2-methyltetrahydrofuran, for the synthesis of O, S, N-heterocyclic compounds.
Article
Biochemistry & Molecular Biology
Jonathan Elie, Corinne Fruit, Thierry Besson
Summary: This paper describes a convenient sequential one-pot approach for the synthesis of a series of 14 pyrazolo[1,5-a][1,3,5]triazines, with advantages in terms of yields, reaction times, and convenient gram scale synthesis compared to traditional methods. The combination of efficient heating using dielectric microwave heating and sequential one-pot reactions eliminates the need for laborious work-up and purification of intermediate compounds, allowing for sustainable synthesis processes.
Review
Chemistry, Medicinal
Thierry Besson, Corinne Fruit
Summary: This review highlights recent synthetic advances in the late-stage C(sp2)-N and C(sp2)-C(sp2) bond-forming reactions under metal-free conditions using diaryliodonium salts as arylating reagents, and discusses their applications in the synthesis of new arylated bioactive heterocyclic compounds.
Article
Pharmacology & Pharmacy
C. Decombat, O. Duval, T. Besson, L. Bourel, M. Pudlo
Summary: The study aimed to define a competency repository in Medicinal Chemistry and provide teaching resources for pharmacy teachers. A comprehensive framework was developed based on a competency-based approach and expert reviews, highlighting the importance of Medicinal Chemistry in pharmacy studies and professional practices.
ANNALES PHARMACEUTIQUES FRANCAISES
(2022)
Article
Chemistry, Medicinal
Joana F. Campos, Thierry Besson, Sabine Berteina-Raboin
Summary: This review lists the structures composed of a pyridopyrimidine moiety that have shown therapeutic interest or have been approved for use as therapeutics. Synthetic protocols for preparing these pyridopyrimidine derivatives are considered. The review is organized into four sections, categorized by the type of pyridopyrimidine. For each compound, the biological activity and synthetic route are presented. The bibliographic research for each type of pyridopyrimidine was conducted using Reaxys and Scifinder.
Article
Chemistry, Organic
Olivier Hebert, Carole Dubouilh-Benard, Joana F. Campos, Sabine Berteina-Raboin, Corinne Fruit, Thierry Besson
Summary: A series of polyfunctionalized 4H-chromenes were synthesized via a microwave-assisted and catalyst-free three-component reaction for the potential precursors of heterocyclic systems with pharmaceutical interest. Raman spectroscopy was used to monitor the microwave-heated reactions, allowing for fast and efficient optimization of process parameters. The study revealed some limitations of this monitoring tool in terms of reaction medium homogeneity. Additionally, the use of bio-sourced and sustainable solvents was investigated, with ethanol found to be the most suitable for this synthesis.
SYNTHESIS-STUTTGART
(2022)
Meeting Abstract
Hematology
V. S. S. Abhinav Ayyadevara, Gerald Wertheim, John Chukinas, Joseph Patrick Loftus, Sung June Lee, Anil Kumar, Rahul S. Bhansali, Srividya Swaminathan, Thierry Besson, Junwei Shi, John D. Crispino, Sarah K. Tasian, Martin P. Carroll, Christian Hurtz
Article
Biochemistry & Molecular Biology
Nathan Broudic, Alexandra Pacheco-Benichou, Corinne Fruit, Thierry Besson
Summary: In this study, a catalytic system involving palladium and copper is reported for the cyclization of N-arylcyanothioformamides and the synthesis of 2-cyanobenzothiazoles. The C-H functionalization/intramolecular C-S bond formation reaction was achieved in the presence of air using 2.0 equiv of an inorganic additive (KI). The reaction led to sole product formation in good yields, allowing the synthesis of various substituted 2-cyanobenzothiazole derivatives that can be used as building blocks for the design of more complex heterocyclic or molecular labeling systems.
Article
Biochemistry & Molecular Biology
Mihaela-Liliana Tintas, Ludovic Peauger, Florent Alix, Cyril Papamicael, Thierry Besson, Jana Sopkova-de Oliveira Santos, Vincent Gembus, Vincent Levacher
Summary: The DYRK family of protein kinases, including DYRK1A and CLK1, are potential therapeutic targets for neurodegenerative diseases such as Alzheimer's disease. In this study, a new class of dihydroquinolines that inhibit hDYRK1A and hCLK1 in the nanomolar range are reported. The most potent inhibitor also exhibits antioxidant and radical scavenging properties, which are relevant in the context of Alzheimer's disease. Drug-likeness and molecular docking studies of these inhibitors are discussed.
Article
Chemistry, Organic
Thomas Delouche, Abdoul Gadiry-Diallo, Thierry Besson, Sensuke Ogoshi, Corinne Fruit
Summary: A practical and sustainable protocol for the synthesis of perfluoroalkylated quinazolin-4(3H)-ones from quinazolin-4(3H)-ones is described. Various substituted or fused-quinazolinones are compatible, yielding mono- and bis-perfluoroalkylated compounds in moderate yields. This photocatalyst-free and visible-light-mediated C-H perfluoroalkylation offers an environmentally friendly approach to novel functionalized quinazolinone scaffolds with potential for drug discovery. Control experiments confirm the involvement of a radical mechanism.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Organic
Nathan Broudic, Alexandra Pacheco-Benichou, Corinne Fruit, Thierry Besson
Summary: The synthesis of trifunctional isomeric benzothiazoles derived from nitroanthranilic acids and their corresponding anthranilonitrile analogues is studied, providing a convenient access to previously unreported 2-cyanobenzothiazoles. A hydrolysis-decarboxylation sequence is then performed in an acidic medium to expand the range of relevant building blocks for further synthetic applications of these poly-functional compounds.
SYNTHESIS-STUTTGART
(2023)
Article
Medicine, Research & Experimental
Kamaleldin E. Elagib, Ashton Brock, Cara M. Clementelli, Goar Mosoyan, Lorrie L. Delehanty, Ranjit K. Sahu, Alexandra Pacheco-Benichou, Corinne Fruit, Thierry Besson, Stephan W. Morris, Koji Eto, Chintan Jobaliya, Deborah L. French, Paul Gadue, Sandeep Singh, Xinrui Shi, Fujun Qin, Robert Cornelison, Hui Li, Camelia lancu-Rubin, Camelia Iancu-Rubin, Adam N. Goldfarb
Summary: Infantile megakaryocytes have limited morphogenesis and low platelet production capacity. Deficiency of MKL1 contributes to this phenotype. Inhibitors of DYRK1A enhance morphogenesis of megakaryocytes and may alleviate clinical problems associated with their limited thrombopoietic capacity.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Meeting Abstract
Radiology, Nuclear Medicine & Medical Imaging
Pauline Poutrel, Fabien Fillesoye, Meziane Ibazizene, Corinne Fruit, Thierry Besson, Cecile Perrio, Fabienne Gourand
NUCLEAR MEDICINE AND BIOLOGY
(2022)
