U1177 holds the regional screening library of 90500 chemical structures, aliquoted in single use copies stored at -20°C (10µL 10mM in DMSO). Original samples are stored in dry form in individual 2D barcoded tubes (MatrixTM).
We also have a library of 2000 compounds of the Pharmacopeia and a continuously growing library of fragments.
Data management is performed thanks to a web-based information system and used in multiple collaborative projects. The system is based on complementary databases interfaced with state of the art softwares:
Accelrys BioRegTM, ChemRegTM, ISIS base TM for compound identification and structures, MS Access TM and Oracle TM for data storage and addressing (alphanumeric data, vectors, images)
Data are entered and manipulated and using Accelrys Pipeline pilot TM, a user-friendly interface developed initially for drug discovery in the pharmaceutical industry.
We use iLabber TM as ELN.
For molecular modeling and 3D-structures viewing we use MOE TM and Pymol TM softwares.
Prevet, H., Moune, M., Tanina, A., Kemmer, C., Herledan, A., Frita, R., Wohlkönig, A., Bourotte, M., Villemagne, B., Leroux, F., Gitzinger, M., Baulard, A. R., Déprez, B., Wintjens, R., Willand, N., & Flipo, M. A fragment-based approach towards the discovery of N-substituted tropinones as inhibitors of Mycobacterium tuberculosis transcriptional regulator EthR2. Eur. J. Med. Chem.,2019, 167: 426-438.10.1016/j.ejmech.2019.02.023
Prevet, H., Flipo, M., Roussel, P., Deprez, B., & Willand, N. Microwave-assisted synthesis of functionalized spirohydantoins as 3-D privileged fragments for scouting the chemical space. Tetrahedron Letters,2016, 57(26): 2888-2894.doi:10.1016/j.tetlet.2016.05.065
Tran, N. C., Dhondt, H., Flipo, M., Deprez, B., & Willand, N. Synthesis of functionalized 2-isoxazolines as three-dimensional fragments for fragment-based drug discovery. Tetrahedron Letters,2015, 56(27): 4119-4123. doi:10.1016/j.tetlet.2015.05.035
Villemagne, B., Flipo, M., Blondiaux, N., Crauste, C., Malaquin, S., Leroux, F., Piveteau, C., Villeret, V., Brodin, P., Villoutreix, B. O., Sperandio, O., Soror, S. H., Wohlkonig, A., Wintjens, R., Deprez, B., Baulard, A. R., & Willand, N. Ligand efficiency driven design of new inhibitors of Mycobacterium tuberculosis transcriptional repressor EthR using fragment growing, merging and linking approaches. Journal of Medicinal Chemistry,2014 57(11): 4876-4888.10.1021/jm500422b
Flipo, M., Willand, N., Lecat-Guillet, N., Hounsou, C., Desroses, M., Leroux, F., Lens, Z., Villeret, V., Wohlkönig, A., Wintjens, R., Christophe, T., Jeon, H. K., Locht, C., Brodin, P., Baulard, A., & Deprez, B. Discovery of novel N-phenyl-phenoxyacetamide derivatives as EthR inhibitors and ethionamide boosters by combining High-Throughput Screening and Synthesis. Journal of Medicinal Chemistry,2012, 55(14): 6391–6402. doi:10.1021/jm300377g
Flipo, M., Beghyn, T., Charton, J., Leroux, V. A., Deprez, B. P., & Deprez-Poulain, R. F. A library of novel hydroxamic acids targeting the metallo-protease family: design, parallel synthesis and screening. Bioorganic and Medicinal Chemistry,2007, 15(1): 63-76. doi:10.1016/j.bmc.2006.10.010
Deprez-Poulain, R. F., Charton, J., Leroux, V., & Deprez, B. P. Convenient synthesis of 4H-1,2,4-triazole-3-thiols using di-2-pyridylthionocarbonate. Tetrahedron Letters,2007, 48(46): 8157-8162. doi:10.1016/j.tetlet.2007.09.094
Charton, J., Leroux, F., Delaroche, S., Landry, V., Deprez, B. P., & Deprez-Poulain, R. F. Synthesis of a Library of 200-Member Squaric Acid N-Hydroxylamide Amides. Bioorganic & Medicinal Chemistry Letters,2008, 18(18): 4968-4971. doi:10.1016/j.bmcl.2008.08.025
Cousaert, N., Willand, N., Gesquiere, J.-C., Tartar, A., Deprez, B., & Deprez-Poulain, R. Original loading and Suzuki conditions for the solid-phase synthesis of biphenyltetrazoles. Application to the first solid-phase synthesis of irbesartan. Tetrahedron Letters,2008, 49: 2743-2747. doi:10.1016/j.tetlet.2008.02.147
Charton, J., Cousaert, N., Bochu, C., Willand, N., Deprez, B., & Deprez-Poulain, R. A versatile solid-phase synthesis of 3-aryl-1,2,4-oxadiazolones and analogues. Tetrahedron Letters,2007, 48(8): 1479-1483. doi:10.1016/j.tetlet.2006.12.050
Malaquin, S., Jida, M., Courtin, J., Laconde, G., Willand, N., Deprez, B., & Deprez-Poulain, R. Water-based conditions for the microscale parallel synthesis of bicyclic lactams. Tetrahedron Letters,2013, 54(6): 562-567.doi:10.1016/j.tetlet.2012.11.082
Jida, M., Malaquin, S., Deprez-Poulain, R., Laconde, G., & Deprez, B. Synthesis of five- and six-membered lactams via solvent-free microwave Ugi reaction. Tetrahedron Letters,2010, 51(39): 5109-5111. doi:10.1016/j.tetlet.2010.07.021
Jida, M., Deprez-Poulain, R., Malaquin, S., Roussel, P., Agbossou-Niedercorn, F., Deprez, B., & Laconde, G. Solvent-free microwave-assisted Meyers’ lactamization. Green Chemistry,2010, 12: 961 - 964. doi:10.1039/B924111F
Camberlein, V., Bosc, D., Gealageas, R., Deprez-Poulain, R., & Deprez, B. New Methodology to Access 1,5-Disubstituted 1,2,3-triazoles 2nd Molecules Medicinal Chemistry Symposium, Barcelona, Spain, 15th-17th May,2019.
Dequirez, G., Bourotte, M., Porras de Francisco, E., Remuiñan, Blanco, M. J., Deprez, B., & Willand, N. Microwave-Assisted Suzuki-Miyaura Cross Coupling using Nickel as Catalyst to Rapidly Access to 3-Arylazetidine. ChemistrySelect,2017, 2(28): 8841-8846.10.1002/slct.201702101. 10.1002/slct.201702101
Probst, N. P., Deprez, B., & Willand, N. Palladium-free Sonogashira-type cross-coupling reaction of bromoisoxazolines or N-alkoxyimidoyl bromides and alkynes. Tetrahedron Letters,2016, 57(10): 1066-1070. doi:10.1016/j.tetlet.2016.01.070
Deprez-Poulain, R., Cousaert, N., Toto, P., Willand, N., & Deprez, B. Application of Ullmann and Ullmann-Finkelstein reactions for the synthesis of N-aryl-N-(1H-pyrazol-3-yl) acetamide or N-(1-aryl-1H-pyrazol-3-yl) acetamide derivatives and pharmacological evaluation. Eur J Med Chem, 2011, 46: 3867-3876. doi:10.1016/j.ejmech.2011.05.056
Toto, P., Gesquiere, J.-C., Cousaert, N., Deprez, B., & Willand, N. UFU (Ullmann-Finkelstein-Ullmann): a new multicomponent reaction. Tetrahedron Letters,2006, 47(28): 4973-4978. doi:10.1016/j.tetlet.2006.04.041
Toto, P., Gesquiere, J.-C., Deprez, B., & Willand, N. Synthesis of N-(iodophenyl)-amides via an unprecedented Ullmann-Finkelstein tandem reaction. Tetrahedron Letters,2006, 47(7): 1181-1186. doi:10.1016/j.tetlet.2005.12.022
Nicolas Cousaert, Patrick Toto, Nicolas Willand, and Benoît Déprez. Efficient, Protection-Free Suzuki-Miyaura Synthesis of ortho-biphenyltetrazoles. Tet Let, 2005, 46, 6529-6532. doi:10.1016/j.tetlet.2005.07.082
Bosc, D., Camberlein, V., Gealageas, R., Castillo-Aguilera, O., Deprez, B., & Deprez-Poulain, R. Kinetic Target-Guided Synthesis: reaching the age of maturity. J. Med. Chem.,2020: in press.10.1021/acs.jmedchem.9b01183
Bosc, D., Jakhlal, J., Deprez, B., & Deprez-Poulain, R. Kinetic target-guided synthesis in drug discovery and chemical biology: a comprehensive facts and figures survey. Future Medicinal Chemistry,2016: 8 (4), 381-404 . doi:10.4155/fmc-2015-0007 OPEN ACCESS
Deprez-Poulain, R., Nathalie, H., Bosc, D., Liang, W. G., Enee, E., Marechal, X., Julie, C., Totobenazara, J., Berte, G., Jahklal, J., Verdelet, T., Dumont, J., Dassonneville, S., Woitrain, E., Gauriot, M., Paquet, C., Duplan, I., Hermant, P., Cantrelle, F.-X., Sevin, E., Culot, M., Landry, V., Herledan, A., Piveteau, C., Lippens, G., Florence, L., Tang, W. J., Van Endert, P., Staels, B., & Deprez, B. Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice. Nature Communications,2015, 6. doi:10.1038/ncomms9250 OPEN ACCESS
Willand, N., Desroses, M., Toto, P., Dirie, B., Lens, Z., Villeret, V., Rucktooa, P., Locht, C., Baulard, A., & Deprez, B. Exploring Drug Target Flexibility Using in Situ Click Chemistry: Application to a Mycobacterial Transcriptional Regulator. ACS Chemical Biology,2010, 5(11): 1007–1013. doi:10.1021/cb100177g
Acidic compounds are under-represented in chemical libraries. Nevertheless, these compounds present interesting bioactivities. Among commercially available drugs, one can notice that acidic functions are essential for several important therapeutic classes like NSAIDs (Non Steroidal Anti-Inflammatory Drugs), sartans and glitazones. Interestingly, these drugs target very different protein classes: enzymes, GPCRs (G-protein coupled receptors) and nuclear hormone receptors. Carboxylic acid and bioisosters are thus important pharmacophoric groups. We have developed and studied new acidic compounds in that perspective.
To synthesize these compounds, we are developing condensation reactions that have a high CsEI (Complexity of synthesis Efficiency Index), derived from Meyers' work or IMCRs (Isonitrile Multi-Component Reactions). Using the repertoire of green protocols we have developed new chemical series that are bioinspired. A strong focus is put on the study of enantio and dia-stereoselectivities and heterocycles.