D. L. Williams, Antimicrobial Agents and Chemotherapy, vol.42, issue.7, pp.1853-1857, 1998.

S. Kushner, The Journal of Organic Chemistry, vol.13, issue.6, pp.834-836, 1948.

S. Kushner, Journal of the American Chemical Society, vol.1952, issue.14, pp.3617-3621

Y. Zhang, International Journal of Tuberculosis and Lung Disease, vol.7, issue.1, pp.6-21, 2003.

Y. Zhang, Journal of Antimicrobial Chemotherapy, vol.52, issue.5, pp.790-795, 2003.

L. Malone, Am Rev Tuberc, vol.65, issue.5, pp.511-518, 1952.

M. M. Wade, Journal of Medical Microbiology, vol.53, issue.8, pp.769-773, 2004.

L. B. Heifets, Antimicrobial Agents and Chemotherapy, vol.33, issue.8, pp.1252-1254, 1989.

Y. Zhang, Journal of Bacteriology, vol.181, issue.7, pp.2044-2049, 1999.

C. Raynaud, Microbiology, vol.145, issue.6, pp.1359-1367, 1999.

. Chapitre1, Tuberculose : Description, Traitements et Perspectives

S. J. Brickner, Journal of Medicinal Chemistry, vol.39, issue.3, pp.673-679, 1996.

L. Alcalá, Antimicrobial Agents and Chemotherapy, vol.47, issue.1, pp.416-417, 2003.

J. C. Rodrí, International Journal of Antimicrobial Agents, vol.20, issue.6, pp.464-467, 2002.

Y. Zhang, Drug Discovery Today, vol.11, issue.1-2, pp.21-27, 2006.

G. F. Schecter, Clinical Infectious Diseases, vol.50, issue.1, pp.49-55, 2010.

, Linezolid (NCT ID: NCT00727844)

, Linezolid (NCT ID: NCT01521364)

M. R. Barbachyn, Journal of Medicinal Chemistry, vol.39, issue.3, pp.680-685, 1996.

J. W. Alffenaar, Antimicrobial Agents and Chemotherapy, vol.55, issue.3, pp.1287-1289, 2011.

R. S. Wallis, Antimicrobial Agents and Chemotherapy, vol.55, issue.2, pp.567-574, 2011.

. Vi-bibliographie-1, F. Denis, and C. Perronne, Mycobacterium tuberculosis et mycobactéries atypiques, Guides MédiBio, 2004.

P. Marquette and P. Lafitte, Tuberculose pulmonaire et primo-infection tuberculeuse

L. Prescott, J. Harley, D. Klein, and . Microbiologie, , 2007.

, World Health Organization, Global Tuberculosis Control Annual Report, 2011.

, World Health Organization, Global Tuberculosis Control Annual Report, 2010.

, Multidrug and extensively drug-resistant TB (M/XDR-TB)

, Global Report on Surveillance and Response, 2010.

L. M. Fu and C. S. Fu-liu, Is Mycobacterium tuberculosis a closer relative to Grampositive or Gram-negative bacterial pathogens? Tuberculosis, vol.82, pp.85-90, 2002.

L. B. Kremer, G. S. Besra, P. J. Brennan, A. R. Baulard, and . Le-lipoarabinomannane, structure et fonctions d'un glycolipide impliqué dans la pathogènie tuberculeuse, 1999.
DOI : 10.4267/10608/1441

M. Faller, M. Niederweis, and G. E. Schulz, The Structure of a Mycobacterial OuterMembrane Channel, Science, issue.5661, pp.1189-1192, 2004.

A. Koul, E. Arnoult, N. Lounis, J. Guillemont, and K. Andries, The challenge of new drug discovery for tuberculosis, Nature, vol.469, issue.7331, pp.483-490, 2011.

A. Schatz and S. A. Waksman, Effect of Streptomycin and Other Antibiotic Substances upon Mycobacterium tuberculosis and Related Organisms, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine, vol.57, issue.2, pp.244-248, 1944.

C. Hinshaw, W. H. Feldman, and K. H. Pfuetze, Treatment of tuberculosis with streptomycin, Journal of the American Medical Association, vol.132, issue.13, pp.778-782, 1946.

Y. L. Janin, Antituberculosis drugs: Ten years of research. Bioorganic and Medicinal Chemistry, vol.15, pp.2479-2513, 2007.
URL : https://hal.archives-ouvertes.fr/pasteur-00166358

D. A. Mitchison, The Diagnosis and Therapy of Tuberculosis During the Past 100

, World Health Organization, Treatment of Tuberculosis Guidelines, Years. American Journal of Respiratory and Critical Care Medicine, vol.171, issue.7, pp.699-706, 2005.

J. Bernstein, W. A. Lott, B. A. Steinberg, and H. L. Yale, Chemotherapy of experimental tuberculosis. V. Isonicotinic acid hydrazide (nydrazid) and related compounds, Am Rev Tuberc, vol.1952, issue.4, pp.357-364

V. Chorine, Action de l'amide nicotinique sur les bacilles du genre Mycobacterium

, Comptes Rendus de l'Académie des Sciences, vol.220, pp.150-151, 1945.

F. G. Winder and P. B. Collins, Inhibition by isoniazid of synthesis of mycolic acids in Mycobacterium tuberculosis, Journal of General Microbiology, vol.63, issue.1, pp.41-48, 1970.

K. Takayama, L. Wang, and H. L. David, Effect of Isoniazid on the In Vivo Mycolic Acid Synthesis, Cell Growth, and Viability of Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.2, issue.1, pp.29-35, 1972.

P. R. Gangadharam, F. M. Harold, and W. B. Schaefer, Selective Inhibition of Nucleic Acid Synthesis in Mycobacterium tuberculosis by Isoniazid, Nature, vol.198, issue.4881, pp.712-714, 1963.

R. Singh, B. Wiseman, T. Deemagarn, L. J. Donald, H. W. Duckworth et al., Catalase-peroxidases (KatG) Exhibit NADH Oxidase Activity, Journal of Biological Chemistry, vol.279, issue.41, pp.43098-43106, 2004.

A. Telenti, P. Imboden, F. Marchesi, L. Matter, K. Schopfer et al., Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis, The Lancet, vol.341, issue.8846, pp.647-651, 1993.

W. Burman and B. Jones, Treatment of HIV-related Tuberculosis in the Era of Effective Antiretroviral Therapy, American Journal of Respiratory and Critical Care Medicine, vol.164, issue.1, pp.7-12, 2001.

A. P. Li, M. K. Reith, A. Rasmussen, J. C. Gorski, S. D. Hall et al., Primary human hepatocytes as a tool for the evaluation of structure-activity relationship in cytochrome P450 induction potential of xenobiotics: evaluation of rifampin, rifapentine and rifabutin, Chemico-Biological Interactions, vol.107, issue.1-2, pp.17-30, 1997.

D. L. Williams, L. Spring, L. Collins, L. P. Miller, L. B. Heifets et al.,

R. J. Gillis and T. P. , Contribution of rpoB Mutations to Development of Rifamycin CrossResistance in Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.42, issue.7, pp.1853-1857, 1998.

S. Kushner, H. Dalalian, R. T. Cassell, J. L. Sanjurjo, D. Mckenzie et al., Experimental Chemotherapy of Tuberculosis. I. Substituted Nicotainamides. The Journal of Organic Chemistry, vol.13, pp.834-836, 1948.

S. Kushner, H. Dalalian, J. L. Sanjurjo, F. L. Bach, S. R. Safir et al., Experimental Chemotherapy of Tuberculosis. II. The Synthesis of Pyrazinamides and Related Compounds, Journal of the American Chemical Society, vol.1952, issue.14, pp.3617-3621

Y. Zhang and D. Mitchison, The curious characteristics of pyrazinamide: a review, International Journal of Tuberculosis and Lung Disease, vol.7, issue.1, pp.6-21, 2003.

Y. Zhang, M. M. Wade, A. Scorpio, H. Zhang, and Z. Sun, Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid, Journal of Antimicrobial Chemotherapy, vol.52, issue.5, pp.790-795, 2003.

L. Malone, A. Schurr, H. Lindh, D. Mckenzie, J. S. Kiser et al., The effect of pyrazinamide (aldinamide) on experimental tuberculosis in mice, Am Rev Tuberc, vol.1952, issue.5, pp.511-518

M. M. Wade and Y. Zhang, Anaerobic incubation conditions enhance pyrazinamide activity against Mycobacterium tuberculosis, Journal of Medical Microbiology, vol.53, issue.8, pp.769-773, 2004.

L. B. Heifets, M. A. Flory, and P. J. Lindholm-levy, Does pyrazinoic acid as an active moiety of pyrazinamide have specific activity against Mycobacterium tuberculosis?, Antimicrobial Agents and Chemotherapy, vol.33, issue.8, pp.1252-1254, 1989.

Y. Zhang, A. Scorpio, H. Nikaido, and Z. Sun, Role of Acid pH and Deficient Efflux of

, Pyrazinoic Acid in Unique Susceptibility of Mycobacterium tuberculosis to Pyrazinamide, Journal of Bacteriology, vol.181, issue.7, pp.2044-2049, 1999.

C. Raynaud, M. Lanéelle, R. H. Senaratne, P. Draper, G. Lanéelle et al., Mechanisms of pyrazinamide resistance in mycobacteria: importance of lack of uptake in addition to lack of pyrazinamidase activity, Microbiology, vol.145, issue.6, pp.1359-1367, 1999.

Y. Zhang, S. Permar, and Z. Sun, Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide, Journal of Medical Microbiology, vol.51, issue.1, pp.42-49, 2002.

A. Scorpio and Y. Zhang, Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus, Nature Medicine, vol.2, issue.6, pp.662-667, 1996.

W. Shi, X. Zhang, X. Jiang, H. Yuan, J. S. Lee et al., Pyrazinamide Inhibits Trans-Translation in Mycobacterium tuberculosis, Science, vol.333, issue.6049, pp.1630-1632, 2011.

K. C. Keiler and N. S. Ramadoss, Bifunctional transfer-messenger RNA, Biochimie, vol.93, issue.11, pp.1993-1997, 2011.

M. Thibonnier, J. Thiberge, and H. -m.;-de-reuse, Trans-Translation in Helicobacter pylori: Essentiality of Ribosome Rescue and Requirement of Protein Tagging for Stress Resistance and Competence, PLoS ONE, vol.3, issue.11, p.3810, 2008.

K. C. Keiler, Biology of trans-Translation. Annual Review of Microbiology, vol.62, issue.1, pp.133-151, 2008.

A. S. Kalinda and C. C. Aldrich, Pyrazinamide: A Frontline Drug Used for Tuberculosis

, Molecular Mechanism of Action Resolved after 50 Years? ChemMedChem, pp.558-560, 2012.

A. Scorpio, P. Lindholm-levy, L. Heifets, R. Gilman, S. Siddiqi et al., Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.41, issue.3, pp.540-543, 1997.

P. Juréen, J. Werngren, J. Toro, and S. Hoffner,

, Gene Mutations in Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.52, issue.5, pp.1852-1854, 2008.

S. Cheng, L. Thibert, T. Sanchez, L. Heifets, and Y. Zhang, pncA Mutations as a Major Mechanism of Pyrazinamide Resistance in Mycobacterium tuberculosis: Spread of a Monoresistant Strain in Quebec, Canada. Antimicrobial Agents and Chemotherapy, vol.44, issue.3, pp.528-532, 2000.

J. P. Thomas, C. O. Baughn, R. G. Wilkinson, and R. G. Shepherd, A new synthetic compound with antituberculous activity in mice: ethambutol (dextro-2,2'-(ethylenediimino)di-l-butanol), Am Rev Respir Dis, vol.83, pp.891-893, 1961.

K. Takayama and J. O. Kilburn, Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis, Antimicrobial Agents and Chemotherapy, vol.33, issue.9, pp.1493-1499, 1989.

K. Mikusová, R. A. Slayden, G. S. Besra, and P. J. Brennan, Biogenesis of the mycobacterial cell wall and the site of action of ethambutol, Antimicrobial Agents and Chemotherapy, vol.39, issue.11, pp.2484-2489, 1995.

A. E. Belanger, G. S. Besra, M. E. Ford, K. Mikusová, J. T. Belisle et al., The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol, Proceedings of the National Academy of Sciences, pp.11919-11924, 1996.

S. Sreevatsan, K. E. Stockbauer, X. Pan, B. N. Kreiswirth, S. L. Moghazeh et al., Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations, Antimicrobial Agents and Chemotherapy, vol.41, issue.8, pp.1677-1681, 1997.

A. Telenti, W. J. Philipp, S. Sreevatsan, C. Bernasconi, K. E. Stockbauer et al., The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol, Nature Medicine, vol.3, issue.5, pp.567-570, 1997.

K. Sharma, M. Gupta, M. Pathak, N. Gupta, A. Koul et al.,

Y. Singh, Transcriptional Control of the Mycobacterial embCAB Operon by PknH through a Regulatory Protein, EmbR, In Vivo, Journal of Bacteriology, vol.188, issue.8, pp.2936-2944, 2006.

G. F. Busscher, F. P. Rutjes, and F. L. Van-delft, 2-Deoxystreptamine: Central Scaffold of Aminoglycoside Antibiotics, Chemical Reviews, vol.105, issue.3, pp.775-792, 2005.

D. Jones, H. J. Metzger, A. Schatz, and S. Waksman, Control of gram-negative bacteria in experimental animals by streptomycin, Science, vol.100, pp.103-105, 1944.

C. R. Spotts and R. Y. Stanier, Mechanism of Streptomycin Action on Bacteria: A Unitary Hypothesis, Nature, vol.192, issue.4803, pp.633-637, 1961.

J. Davies, L. Gorini, and B. Davis, Misreading of RNA Codewords Induced by Aminoglycoside Antibiotics, Molecular Pharmacology, vol.1, issue.1, pp.93-106, 1965.

. Chapitre1, Tuberculose : Description, Traitements et Perspectives 99

R. T. Garvin, D. K. Biswas, and L. Gorini, The Effects of Streptomycin or

, Dihydrostreptomycin Binding to 16S RNA or to 30S Ribosomal Subunits, Proceedings of the National Academy of Sciences, pp.3814-3818, 1974.

A. P. Carter, W. M. Clemons, D. E. Brodersen, R. J. Morgan-warren, and B. Wimberly,

T. Ramakrishnan and V. , Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics, Nature, vol.407, issue.6802, pp.340-348, 2000.

M. Finken, P. Kirschner, A. Meier, A. Wrede, and E. C. Böttger, Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot, Molecular Microbiology, vol.9, issue.6, pp.1239-1246, 1993.

C. E. Maus, B. B. Plikaytis, and T. M. Shinnick, Molecular Analysis of Cross-Resistance to Capreomycin, Kanamycin, Amikacin, and Viomycin in Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.49, issue.8, pp.3192-3197, 2005.

S. K. Johansen, C. E. Maus, B. B. Plikaytis, and S. Douthwaite, Capreomycin Binds across the Ribosomal Subunit Interface Using tlyA-Encoded 22-O-Methylations in 16S and 23S rRNAs, Molecular Cell, vol.23, issue.2, pp.173-182, 2006.

. Amikacin, Tuberculosis, vol.88, issue.2, pp.87-88, 2008.

. Kanamycin, Tuberculosis, vol.88, issue.2, pp.117-118, 2008.

. Capreomycin, Tuberculosis, vol.88, issue.2, pp.89-91, 2008.

Y. I. Ho, C. Y. Chan, and A. F. Cheng, In-vitro activities of aminoglycosideaminocyclitols against mycobacteria, Journal of Antimicrobial Chemotherapy, vol.40, issue.1, pp.27-32, 1997.

L. A. Mitscher, Bacterial Topoisomerase Inhibitors: Quinolone and Pyridone Antibacterial Agents, Chemical Reviews, vol.105, issue.2, pp.559-592, 2005.

G. Y. Lesher, E. J. Froelich, M. D. Gruett, J. H. Bailey, and R. P. Brundage, 1,8Naphtyridine Derivatives. A New Class of Chemotherapeutic Agents, vol.91, pp.1063-1065, 1962.

W. H. Deitz, J. H. Bailey, and E. J. Froelich, In Vitro Antibacterial Properties of Nalidixic Acid, a New Drug Active against Gram-Negative Organisms, Antimicrobial Agents and Chemotherapy, vol.161, pp.583-587, 1963.

A. Sugino, C. L. Peebles, K. N. Kreuzer, and N. R. Cozzarelli, Mechanism of action of nalidixic acid: Purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme, Proceedings of the National Academy of Sciences, vol.74, issue.11, pp.4767-4771, 1977.

A. B. Khodursky and N. R. Cozzarelli, The Mechanism of Inhibition of Topoisomerase IV by Quinolone Antibacterials, Journal of Biological Chemistry, vol.273, issue.42, pp.27668-27677, 1998.

A. Aubry, X. Pan, L. M. Fisher, V. Jarlier, and E. Cambau, Mycobacterium tuberculosis DNA Gyrase: Interaction with Quinolones and Correlation with Antimycobacterial Drug Activity, Antimicrobial Agents and Chemotherapy, vol.48, issue.4, pp.1281-1288, 2004.

H. E. Takiff, L. Salazar, C. Guerrero, W. Philipp, W. M. Huang et al., Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations, Antimicrobial Agents and Chemotherapy, vol.38, issue.4, pp.773-780, 1994.

L. Jörgen, Para-aminosalycilic acid in the treatment of tuberculosis, The Lancet, vol.247, issue.6384, pp.15-16, 1946.

V. Nopponpunth, W. Sirawaraporn, P. J. Greene, and D. V. Santi, Cloning and Expression of Mycobacterium tuberculosis and Mycobacterium leprae Dihydropteroate Synthase in Escherichia coli, Journal of Bacteriology, vol.181, issue.21, pp.6814-6821, 1999.

. Chapitre1, Tuberculose : Description, Traitements et Perspectives

S. Feuerriegel, C. Köser, L. Trübe, J. Archer, S. Rüsch-gerdes et al., Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance, Antimicrobial Agents and Chemotherapy, vol.54, issue.11, pp.4794-4798, 2010.

V. Mathys, R. Wintjens, P. Lefevre, J. Bertout, A. Singhal et al., Molecular Genetics of para-Aminosalicylic Acid Resistance in Clinical Isolates and Spontaneous Mutants of Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.53, issue.5, pp.2100-2109, 2009.

C. Ratledge and K. A. Brown, Inhibition of mycobactin formation in Mycobacterium smegmatis by p-aminosalicylate. A new proposal for the mode of action of p-aminosalicylate, American Review of Respiratory Disease, vol.106, issue.5, pp.774-776, 1972.

K. A. Brown and C. Ratledge, The effect of p-aminosalicyclic acid on iron transport and assimilation in mycobacteria, Biochimica et Biophysica Acta (BBA)-General Subjects, vol.385, issue.2, pp.207-220, 1975.

T. Adilakshmi, P. D. Ayling, and C. Ratledge, Mutational Analysis of a Role for Salicylic Acid in Iron Metabolism of Mycobacterium smegmatis, Journal of Bacteriology, vol.182, issue.2, pp.264-271, 2000.

R. Colin, Iron, mycobacteria and tuberculosis, Tuberculosis, vol.84, issue.1-2, pp.110-130, 2004.

H. L. David, K. Takayama, and D. S. Goldman, Susceptibility of mycobacterial Dalanyl-D-alanine synthetase to D-cycloserine, American Review of Respiratory Disease, vol.100, issue.4, pp.579-581, 1969.

Z. Feng and R. G. Barletta, Roles of Mycobacterium smegmatis d-Alanine:d-Alanine Ligase and d-Alanine Racemase in the Mechanisms of Action of and Resistance to the Peptidoglycan Inhibitor d-Cycloserine, Antimicrobial Agents and Chemotherapy, vol.47, issue.1, pp.283-291, 2003.

O. Chacon, Z. Feng, N. B. Harris, N. E. Cáceres, L. G. Adams et al., Mycobacterium smegmatis d-Alanine Racemase Mutants Are Not Dependent on d-Alanine for Growth, Antimicrobial Agents and Chemotherapy, vol.46, issue.1, pp.47-54, 2002.

A. E. Belanger, J. C. Porter, and G. F. Hatfull, Genetic Analysis of Peptidoglycan Biosynthesis in Mycobacteria: Characterization of a ddlA Mutant of Mycobacterium smegmatis, Journal of Bacteriology, vol.182, issue.23, pp.6854-6856, 2000.

L. T. Thompson, J. R. Moskal, and J. F. Disterhoft, Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine, Nature, vol.359, issue.6396, pp.638-641, 1992.

P. Lemagueres, H. Im, J. Ebalunode, U. Strych, M. J. Benedik et al., The 1.9 Å Crystal Structure of Alanine Racemase from Mycobacterium tuberculosis Contains a Conserved Entryway into the Active Site, Biochemistry, vol.44, issue.5, pp.1471-1481, 2005.

F. G. Winder, P. B. Collins, and D. Whelan, Effects of Ethionamide and Isoxyl on Mycolic Acid Synthesis in Mycobacterium tuberculosis BCG, Journal of General Microbiology, vol.66, issue.3, pp.379-380, 1971.

A. E. Debarber, K. Mdluli, M. Bosman, L. Bekker, and C. E. Barry, Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis, Proceedings of the National Academy of Sciences, issue.17, pp.9677-9682, 2000.

T. A. Vannelli, A. Dykman, and P. R. Ortiz-de-montellano, The Antituberculosis Drug Ethionamide Is Activated by a Flavoprotein Monooxygenase, Journal of Biological Chemistry, vol.277, issue.15, pp.12824-12829, 2002.

A. R. Baulard, J. C. Betts, J. Engohang-ndong, S. Quan, R. A. Mcadam et al., Activation of the Pro-drug Ethionamide Is Regulated in Mycobacteria, Journal of Biological Chemistry, vol.275, issue.36, pp.28326-28331, 2000.

. Chapitre1, Tuberculose : Description, Traitements et Perspectives

. Gatifloxacin, ID: NCT00216385) clinicaltrials.gov

. Moxifloxacin, ID: NCT00864383) clinicaltrials.gov

K. Andries, P. Verhasselt, J. Guillemont, H. W. Göhlmann, J. Neefs et al., A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis, Science, issue.5707, pp.223-227, 2005.

A. Koul, N. Dendouga, K. Vergauwen, B. Molenberghs, L. Vranckx et al., Diarylquinolines target subunit c of mycobacterial ATP synthase, Nature Chemical Biology, vol.3, issue.6, pp.323-324, 2007.

A. C. Haagsma, R. Abdillahi-ibrahim, M. J. Wagner, K. Krab, K. Vergauwen et al., Selectivity of TMC207 towards Mycobacterial ATP Synthase Compared with That towards the Eukaryotic Homologue, Antimicrobial Agents and Chemotherapy, vol.53, issue.3, pp.1290-1292, 2009.

, TMC207 (NCT ID: NCT01464762), clinicaltrials.gov

D. I. Edwards, Mechanism of antimicrobial action of metronidazole, Journal of Antimicrobial Chemotherapy, vol.5, issue.5, pp.499-502, 1979.

L. G. Wayne and H. A. Sramek, Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.38, issue.9, pp.2054-2058, 1994.

J. V. Brooks, S. K. Furney, and I. M. Orme, Metronidazole Therapy in Mice Infected with Tuberculosis, Antimicrobial Agents and Chemotherapy, vol.43, issue.5, pp.1285-1288, 1999.

. Metronidazole, ID: NCT00425113) clinicaltrials.gov

M. Matsumoto, H. Hashizume, T. Tomishige, M. Kawasaki, H. Tsubouchi et al., OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice, PLoS Med, vol.3, issue.11, pp.1285-1288, 2006.

C. K. Stover, P. Warrener, D. R. Vandevanter, D. R. Sherman, T. M. Arain et al., A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis, Nature, issue.6789, pp.962-966, 2000.

U. H. Manjunatha, H. Boshoff, C. S. Dowd, L. Zhang, T. J. Albert et al., Identification of a nitroimidazo-oxazinespecific protein involved in PA-824 resistance in Mycobacterium tuberculosis, Proceedings of the National Academy of Sciences, vol.103, issue.2, pp.431-436, 2006.

R. Singh, U. Manjunatha, H. I. Boshoff, Y. H. Ha, P. Niyomrattanakit et al., PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release, Science, vol.322, issue.5906, pp.1392-1395, 2008.

U. Manjunatha, H. I. Boshoff, and C. E. Barry, The mechanism of action of PA-824: Novel insights from transcriptional profiling, Communicative and Integrative Biology, vol.2, issue.3, pp.215-223, 2009.

, OPC-67683 (NCT ID: NCT01131351) clinicaltrials.gov

, OPC-67683 (NCT ID: NCT01424670) clinicaltrials.gov

P. , NCT ID: NCT01498419) clinicaltrials.gov

M. Protopopova, C. Hanrahan, B. Nikonenko, R. Samala, P. Chen et al., Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines, Journal of Antimicrobial Chemotherapy, vol.56, issue.5, pp.968-974, 2005.

R. E. Lee, M. Protopopova, E. Crooks, R. A. Slayden, M. Terrot et al., Combinatorial Lead Optimization of [1,2]-Diamines Based on Ethambutol as Potential Antituberculosis Preclinical Candidates, Journal of Combinatorial Chemistry, vol.5, issue.2, pp.172-187, 2003.

L. Jia, L. Coward, G. S. Gorman, P. E. Noker, and J. E. Tomaszewski, Pharmacoproteomic Effects of Isoniazid, Ethambutol, and N-Geranyl-N?-(2adamantyl)ethane-1,2-diamine (SQ109) on Mycobacterium tuberculosis H37Rv, Journal of Pharmacology and Experimental Therapeutics, vol.315, issue.2, pp.905-911, 2005.

, SQ109 (NCT ID: NCT01218217) clinicaltrials.gov

, SQ109 (NCT ID: NCT01252108) clinicaltrials.gov

S. J. Brickner, D. K. Hutchinson, M. R. Barbachyn, P. R. Manninen, D. A. Ulanowicz et al., Synthesis and Antibacterial Activity of U-100592 and U-100766, Two Oxazolidinone Antibacterial Agents for the Potential Treatment of Multidrug-Resistant Gram-Positive Bacterial Infections, Journal of Medicinal Chemistry, vol.39, issue.3, pp.673-679, 1996.

L. Alcalá, M. J. Ruiz-serrano, C. Pérez-fernández-turégano, D. García-de-viedma, M. Díaz-infantes et al., In Vitro Activities of Linezolid against Clinical Isolates of Mycobacterium tuberculosis That Are Susceptible or Resistant to FirstLine Antituberculous Drugs, Antimicrobial Agents and Chemotherapy, vol.47, issue.1, pp.416-417, 2003.

J. C. Rodrí-guez, M. Ruiz, M. López, and G. Royo, In vitro activity of moxifloxacin, levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis, International Journal of Antimicrobial Agents, vol.20, issue.6, pp.464-467, 2002.

Y. Zhang, K. Post-martens, and S. Denkin, New drug candidates and therapeutic targets for tuberculosis therapy, Drug Discovery Today, vol.11, issue.1-2, pp.21-27, 2006.

G. F. Schecter, C. Scott, L. True, A. Raftery, J. Flood et al., Linezolid in the Treatment of Multidrug-Resistant Tuberculosis, Clinical Infectious Diseases, vol.50, issue.1, pp.49-55, 2010.

. Linezolid, ID: NCT00727844) clinicaltrials.gov

. Linezolid, ID: NCT01521364) clinicaltrials.gov

M. R. Barbachyn, D. K. Hutchinson, S. J. Brickner, M. H. Cynamon, J. O. Kilburn et al., Identification of a Novel Oxazolidinone (U-100480) with Potent Antimycobacterial Activity, Journal of Medicinal Chemistry, vol.39, issue.3, pp.680-685, 1996.

J. W. Alffenaar, T. Van-der-laan, S. Simons, and T. S. Van-der-werf,

P. J. Kasteele, H. De-neeling, and D. Van-soolingen, Susceptibility of Clinical Mycobacterium tuberculosis Isolates to a Potentially Less Toxic Derivate of Linezolid, p.100480

, Antimicrobial Agents and Chemotherapy, vol.55, issue.3, pp.1287-1289, 2011.

R. S. Wallis, W. Jakubiec, V. Kumar, G. Bedarida, A. Silvia et al., Biomarker-Assisted Dose Selection for Safety and Efficacy in Early Development of PNU-100480 for Tuberculosis, Antimicrobial Agents and Chemotherapy, vol.55, issue.2, pp.567-574, 2011.

, PNU-100480 (NCT ID: NCT01225640) clinicaltrials.gov

, AZD5847 (NCT ID: NCT01516203) clinicaltrials.gov

G. D. Wright and A. D. Sutherland, New strategies for combating multidrug-resistant bacteria. Trends in molecular medicine, vol.13, pp.260-267, 2007.
DOI : 10.1016/j.molmed.2007.04.004

A. L. Koch, Bacterial Wall as Target for Attack, Clinical Microbiology Reviews, vol.16, issue.4, pp.673-687, 2003.

S. M. Drawz and R. A. Bonomo, Three Decades of ?-Lactamase Inhibitors, Clinical Microbiology Reviews, vol.23, issue.1, pp.160-201, 2010.

H. F. Chambers, D. Moreau, D. Yajko, C. Miick, C. Wagner et al., Can penicillins and other betalactam antibiotics be used to treat tuberculosis?, Antimicrobial Agents and Chemotherapy, vol.39, issue.12, pp.2620-2624, 1995.
DOI : 10.1128/aac.39.12.2620

URL : https://aac.asm.org/content/39/12/2620.full.pdf

V. Jarlier, L. Gutmann, and H. Nikaido, Interplay of cell wall barrier and beta-lactamase activity determines high resistance to beta-lactam antibiotics in Mycobacterium chelonae, Antimicrobial Agents and Chemotherapy, vol.35, issue.9, pp.1937-1939, 1991.

B. Quinting, J. Reyrat, D. Monnaie, G. Amicosante, V. Pelicic et al., Contribution of ?-lactamase production to the resistance of mycobacteria to ?-lactam antibiotics, FEBS letters, vol.406, issue.3, pp.275-278, 1997.

T. Mukherjee, D. Basu, S. Mahapatra, C. Goffin, J. Van-beeumen et al., Biochemical characterization of the 49 kDa penicillin-binding protein of Mycobacterium smegmatis, Biochemical Journal, vol.320, issue.1, pp.197-200, 1996.

R. K. Voladri, D. L. Lakey, S. H. Hennigan, B. E. Menzies, K. M. Edwards et al., Recombinant Expression and Characterization of the Major ?-Lactamase of Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.42, issue.6, pp.1375-1381, 1998.

F. Wang, C. Cassidy, and J. C. Sacchettini, Crystal Structure and Activity Studies of the Mycobacterium tuberculosis ?-Lactamase Reveal Its Critical Role in Resistance to ?-Lactam Antibiotics, Antimicrobial Agents and Chemotherapy, vol.50, issue.8, pp.2762-2771, 2006.

K. M. Nampoothiri, R. Rubex, A. K. Patel, S. S. Narayanan, S. Krishna et al., Molecular cloning, overexpression and biochemical characterization of hypothetical ?-lactamases of Mycobacterium tuberculosis H37Rv, Journal of Applied Microbiology, vol.105, issue.1, pp.59-67, 2008.

A. R. Flores, L. M. Parsons, and M. S. Pavelka, Genetic analysis of the ?-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to ?-lactam antibiotics, Microbiology, vol.151, issue.2, pp.521-532, 2005.

J. Hugonnet, L. W. Tremblay, H. I. Boshoff, C. E. Barry, and J. S. Blanchard, Meropenem-Clavulanate Is Effective Against Extensively Drug-Resistant Mycobacterium tuberculosis, Science, vol.323, issue.5918, pp.1215-1218, 2009.
DOI : 10.1126/science.1167498

URL : http://europepmc.org/articles/pmc2679150?pdf=render

H. F. Chambers, T. Kocagöz, T. Sipit, J. Turner, and P. C. Hopewell, Activity of Amoxicillin/Clavulanate in Patients with Tuberculosis, Clinical Infectious Diseases, vol.26, issue.4, pp.874-877, 1998.

N. Dauby, I. Muylle, F. Mouchet, R. Sergysels, and M. Payen, Meropenem/Clavulanate and Linezolid Treatment for Extensively Drug-resistant Tuberculosis, The Pediatric Infectious Disease Journal, vol.30, issue.9, pp.812-813, 2011.

C. Sala, A. Haouz, F. A. Saul, I. Miras, I. Rosenkrands et al., Genome-wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis, Molecular Microbiology, vol.71, issue.5, pp.1102-1116, 2009.

K. A. Wolff, M. Sherman, and L. Nguyen, Potentiation of Available Antibiotics by Targeting Resistance-An Emerging Trend in Tuberculosis Drug Development, 2011.

M. W. Fraaije, N. M. Kamerbeek, A. J. Heidekamp, R. Fortin, and D. B. Janssen, The Prodrug Activator EtaA from Mycobacterium tuberculosis Is a Baeyer-Villiger Monooxygenase, Journal of Biological Chemistry, vol.279, issue.5, pp.3354-3360, 2004.

X. Hanoulle, J. Wieruszeski, P. Rousselot-pailley, I. Landrieu, C. Locht et al., Selective intracellular accumulation of the major metabolite issued from the activation of the prodrug ethionamide in mycobacteria, Journal of Antimicrobial Chemotherapy, vol.58, issue.4, pp.768-772, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00103724

F. Wang, R. Langley, G. Gulten, L. G. Dover, G. S. Besra et al., Mechanism of thioamide drug action against tuberculosis and leprosy, The Journal of Experimental Medicine, vol.204, issue.1, pp.73-78, 2007.
DOI : 10.1084/jem.20062100

URL : http://jem.rupress.org/content/204/1/73.full.pdf

H. Aramaki, N. Yagi, and M. Suzuki, Residues important for the function of a multihelical DNA binding domain in the new transcription factor family of Cam and Tet repressors, Protein Engineering, vol.8, issue.12, pp.1259-1266, 1995.

J. Engohang-ndong, D. Baillat, M. Aumercier, F. Bellefontaine, G. S. Besra et al., EthR, a repressor of the TetR/CamR family implicated in ethionamide resistance in mycobacteria, octamerizes cooperatively on its operator, Molecular Microbiology, vol.51, issue.1, pp.175-188, 2004.

J. L. Ramos, M. Martínez-bueno, A. J. Molina-henares, W. Terán, K. Watanabe et al., The TetR Family of Transcriptional Repressors, Microbiology and Molecular Biology Reviews, vol.69, issue.2, pp.326-356, 2005.
DOI : 10.1128/mmbr.69.2.326-356.2005

URL : https://mmbr.asm.org/content/69/2/326.full.pdf

L. G. Dover, P. E. Corsino, I. R. Daniels, S. L. Cocklin, V. Tatituri et al., Crystal Structure of the TetR/CamR Family Repressor Mycobacterium tuberculosis EthR Implicated in Ethionamide Resistance, Journal of Molecular Biology, vol.340, issue.5, pp.1095-1105, 2004.

F. Frénois, J. Engohang-ndong, C. Locht, A. R. Baulard, and V. Villeret, Structure of EthR in a Ligand Bound Conformation Reveals Therapeutic Perspectives against Tuberculosis, Molecular Cell, vol.16, issue.2, pp.301-307, 2004.

W. Weber, R. Schoenmakers, B. Keller, M. Gitzinger, T. Grau et al., A synthetic mammalian gene circuit reveals antituberculosis compounds, Proceedings of the National Academy of Sciences, issue.29, pp.9994-9998, 2008.
DOI : 10.1073/pnas.0800663105

URL : http://www.pnas.org/content/105/29/9994.full.pdf

M. Fussenegger, W. Weber, and R. Schoenmakers, Composition for Treatment of Tuberculosis, 2009.

T. Grau, P. Selchow, M. Tigges, R. Burri, M. Gitzinger et al., Phenylethyl Butyrate Enhances the Potency of Second-Line Drugs against Clinical Isolates of Mycobacterium tuberculosis, Antimicrobial Agents and Chemotherapy, vol.56, issue.2, pp.1142-1145, 2012.

N. Willand, B. Dirie, X. Carette, P. Bifani, A. Singhal et al., Synthetic EthR inhibitors boost antituberculous activity of ethionamide, Nature Medicine, vol.15, issue.5, pp.537-544, 2009.
DOI : 10.1038/nm.1950

M. Flipo, M. Desroses, N. Lecat-guillet, B. Dirié, X. Carette et al., Ethionamide Boosters: Synthesis, Biological Activity, and Structure?Activity Relationships of a Series of 1,2,4-Oxadiazole EthR Inhibitors, Journal of Medicinal Chemistry, vol.54, issue.8, pp.2994-3010, 2011.

M. Flipo, M. Desroses, N. Lecat-guillet, B. Villemagne, N. Blondiaux et al., Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors, Journal of Medicinal Chemistry, vol.55, issue.1, pp.68-83, 2011.

N. Willand, M. Desroses, P. Toto, B. Dirié, Z. Lens et al., Exploring Drug Target Flexibility Using in Situ Click Chemistry: Application to a Mycobacterial Transcriptional Regulator, ACS Chemical Biology, vol.2010, issue.11, pp.1007-1013
DOI : 10.1021/cb100177g

. Ii-bibliographie,

R. Macarron, Critical review of the role of HTS in drug discovery, Drug Discovery Today, vol.11, issue.7-8, pp.277-279, 2006.

D. Brown and G. Superti-furga, Rediscovering the sweet spot in drug discovery, Drug Discovery Today, vol.8, issue.23, pp.1067-1077, 2003.

C. G. Wermuth, The practice of medicinal chemistry-Third edition, 2008.

R. S. Bohacek, C. Mcmartin, and W. C. Guida, The art and practice of structure-based drug design: A molecular modeling perspective, Medicinal Research Reviews, vol.16, issue.1, pp.3-50, 1996.

C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Advanced Drug Delivery Reviews, vol.23, issue.1-3, pp.3-25, 1997.

D. F. Veber, S. R. Johnson, H. Cheng, B. R. Smith, K. W. Ward et al., Molecular Properties That Influence the Oral Bioavailability of Drug Candidates, Journal of Medicinal Chemistry, vol.45, issue.12, pp.2615-2623, 2002.

S. B. Shuker, P. J. Hajduk, R. P. Meadows, and S. W. Fesik, Discovering High-Affinity Ligands for Proteins: SAR by NMR, Science, vol.274, issue.5292, pp.1531-1534, 1996.
DOI : 10.1126/science.274.5292.1531

P. J. Hajduk, G. Sheppard, D. G. Nettesheim, E. T. Olejniczak, S. B. Shuker et al., Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR, Journal of the American Chemical Society, vol.119, issue.25, pp.5818-5827, 1997.
DOI : 10.1021/ja9702778

M. M. Hann, A. R. Leach, and G. Harper, Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery, Journal of Chemical Information and Computer Sciences, issue.3, pp.856-864, 2001.

P. J. Hajduk and J. Greer, A decade of fragment-based drug design: strategic advances and lessons learned, Nature Reviews Drug Discovery, vol.6, issue.3, pp.211-219, 2007.
DOI : 10.1038/nrd2220

M. Congreve, R. Carr, C. Murray, and H. Jhoti, A "Rule of Three" for fragment-based lead discovery? Drug Discovery Today, vol.8, pp.876-877, 2003.

D. C. Rees, M. Congreve, C. W. Murray, and R. Carr, Fragment-based lead discovery, Nature Reviews Drug Discovery, vol.3, issue.8, pp.660-672, 2004.

A. L. Hopkins, C. R. Groom, and A. Alex, Ligand efficiency: a useful metric for lead selection, Drug Discovery Today, vol.9, issue.10, pp.430-431, 2004.
DOI : 10.1016/s1359-6446(04)03069-7

R. A. Carr, M. Congreve, C. W. Murray, and D. C. Rees, Fragment-based lead discovery: leads by design, Drug Discovery Today, vol.10, issue.14, pp.987-892, 2005.
DOI : 10.1016/s1359-6446(05)03511-7

P. D. Leeson and B. Springthorpe, The influence of drug-like concepts on decisionmaking in medicinal chemistry, Nature Reviews Drug Discovery, vol.6, issue.11, pp.881-890, 2007.

G. M. Keserü and G. M. Makara, The influence of lead discovery strategies on the properties of drug candidates, Nature Reviews Drug Discovery, vol.8, issue.3, pp.203-212, 2009.

Á. Tarcsay, K. Nyíri, and G. M. Keserü, Impact of Lipophilic Efficiency on Compound Quality, Journal of Medicinal Chemistry, vol.2012, issue.3, pp.1252-1260
DOI : 10.1021/jm201388p

P. Mortenson and C. Murray, Assessing the lipophilicity of fragments and early hits, Journal of Computer-Aided Molecular Design, vol.25, issue.7, pp.663-667, 2011.
DOI : 10.1007/s10822-011-9435-z

M. L. Verdonk and D. C. Rees, Group Efficiency: A Guideline for Hits-to-Leads Chemistry, ChemMedChem, vol.3, issue.8, pp.1179-1180, 2008.
DOI : 10.1002/cmdc.200800132

C. Abad-zapatero, Ligand efficiency indices for effective drug discovery, Expert Opinion on Drug Discovery, vol.2, issue.4, pp.469-488, 2007.
DOI : 10.1517/17460441.2.4.469

V. I. Bibliographie,

M. Flipo, M. Desroses, N. Lecat-guillet, B. Dirié, X. Carette et al., Ethionamide Boosters: Synthesis, Biological Activity, and Structure?Activity Relationships of a Series of 1,2,4-Oxadiazole EthR Inhibitors, Journal of Medicinal Chemistry, vol.54, issue.8, pp.2994-3010, 2011.

S. Michiharu, S. Yumi, K. Nobuhito, S. Yuko, N. Hiroshi et al., Synthesis of thiazole, oxazole and heterocyclic ring-substituted 1,2-dioxanes, Journal of Heterocyclic Chemistry, vol.37, issue.2, pp.269-274, 2000.

D. Dunn, J. Husten, M. A. Ator, and S. Chatterjee,

, Bioorganic and Medicinal Chemistry Letters, vol.17, pp.542-545, 2007.

N. Irako, Y. Hamada, and T. Shioiri, A New Asymmetric Synthesis of (S)-Dolaphenine and Its Heteroaromatic Congeners Utilizing (+)-2-Hydroxy-3-pinanone and (-)-3-Hydroxy-2caranone as Chiral Auxiliaries, Tetrahedron, issue.46, pp.12731-12744, 1995.

C. A. Bernhart, P. M. Perreaut, B. P. Ferrari, Y. A. Muneaux, J. L. Assens et al., A new series of imidazolones: highly specific and potent nonpeptide AT1 angiotensin II receptor antagonists, Journal of Medicinal Chemistry, vol.36, issue.22, pp.3371-3380, 1993.

L. A. Smyth, T. P. Matthews, P. N. Horton, M. B. Hursthouse, and I. Collins, Divergent cyclisations of 2-(5-amino-4-carbamoyl-1H-pyrazol-3-yl)acetic acids with formyl and acetyl electrophiles, Tetrahedron, vol.63, issue.39, pp.9627-9634, 2007.

W. K. Hagmann, The Many Roles for Fluorine in Medicinal Chemistry, Journal of Medicinal Chemistry, vol.51, issue.15, pp.4359-4369, 2008.

J. M. Domagala, L. D. Hanna, C. L. Heifetz, M. P. Hutt, T. F. Mich et al., New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay, Journal of Medicinal Chemistry, vol.29, issue.3, pp.394-404, 1986.

K. Müller, C. Faeh, and F. Diederich, Fluorine in Pharmaceuticals: Looking Beyond Intuition, Science, issue.5846, pp.1881-1886, 2007.

F. Luo and A. Jeevanandam, Simple transformation of nitrile into ester by the use of chlorotrimethylsilane, Tetrahedron Letters, vol.39, issue.51, pp.9455-9456, 1998.

F. Bellina, S. Cauteruccio, and R. Rossi, Palladium-and Copper-Mediated

, Arylation of Azoles-Including Free (NH)-Imidazole,-Benzimidazole and-Indole-Under Base-Free and Ligandless Conditions, ChemInform, issue.26, p.37, 2006.

J. K. Augustine, V. Vairaperumal, S. Narasimhan, P. Alagarsamy, and A. Radhakrishnan, Propylphosphonic anhydride (T3P®): an efficient reagent for the one, Tetrahedron, vol.65, issue.48, pp.9989-9996, 2009.

H. Wissmann and H. Kleiner, New Peptide Synthesis, Angewandte Chemie International Edition in English, vol.19, issue.2, pp.133-134, 1980.

S. Kajigaeshi, T. Kakinami, M. Moriwaki, S. Fujisaki, K. Maeno et al., Alpha-chlorination of aromatic acetyl derivatives with Benzyltrimethylammonium Dichloroiodate, Synthesis, pp.545-546, 1988.

D. K. Dalvie, A. S. Kalgutkar, S. C. Khojasteh-bakht, R. S. Obach, and J. P. Donnell, Biotransformation Reactions of Five-Membered Aromatic Heterocyclic Rings, Chemical Research in Toxicology, vol.15, issue.3, pp.269-299, 2002.

T. Mizutani, K. Yoshida, and S. Kawazoe, Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Identification of thioamides as ring cleavage products. Drug Metabolism and Disposition, vol.22, pp.750-755, 1994.

T. Mizutani and K. Suzuki, Relative hepatotoxicity of 2-(substituted phenyl)thiazoles and substituted thiobenzamides in mice: evidence for the involvement of thiobenzamides as ring cleavage metabolites in the hepatotoxicity of 2-phenylthiazoles, Toxicology Letters, vol.85, issue.2, pp.101-105, 1996.

G. J. Stevens, K. Hitchcock, Y. K. Wang, G. M. Coppola, R. W. Versace et al., In Vitro Metabolism of N-(5-Chloro2-methylphenyl)-N'-(2-methylpropyl)thiourea: Species Comparison and Identification of a Novel Thiocarbamide-Glutathione Adduct, Chemical Research in Toxicology, vol.10, issue.7, pp.733-741, 1997.

C. Bolea, Novel thiazoles derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors, 2010.

E. Fuglseth, T. H. Thvedt, M. F. Møll, and B. H. Hoff, Electrophilic and nucleophilic side chain fluorination of para-substituted acetophenones, Tetrahedron, vol.64, pp.7318-7323, 2008.

T. Paul, N. Sergio-gonzalez, D. Michael, D. , B. Stéphane et al., Selectfluor: Mechanistic Insight and Applications, Angewandte Chemie International Edition, vol.44, pp.192-212, 2005.

J. Legros, G. Primault, and J. Fiaud, Syntheses of acetylquinolines and acetylisoquinolines via palladium-catalyzed coupling reactions, Tetrahedron, vol.57, issue.13, pp.2507-2514, 2001.
DOI : 10.1016/s0040-4020(01)00076-x

J. K. Stille, The Palladium-Catalyzed Cross-Coupling Reactions of Organotin Reagents with Organic Electrophiles

, Angewandte Chemie International Edition in English, vol.25, issue.6, pp.508-524, 1986.

H. Zhang, S. Kasibhatla, J. Kuemmerle, W. Kemnitzer, K. Ollis-mason et al., Discovery and Structure?Activity Relationship of 3-Aryl-5-aryl-1,2,4-oxadiazoles as a New Series of Apoptosis Inducers and Potential Anticancer Agents, Journal of Medicinal Chemistry, vol.48, issue.16, pp.5215-5223, 2005.

J. C. Lee, H. J. Choi, and Y. C. Lee, Efficient synthesis of multi-substituted oxazoles under solvent-free microwave irradiation, Tetrahedron Letters, vol.44, issue.1, pp.123-125, 2003.

W. Porcal, P. Hernández, M. González, A. Ferreira, C. Olea-azar et al., Heteroarylnitrones as Drugs for Neurodegenerative Diseases: Synthesis, Neuroprotective Properties, and Free Radical Scavenger Properties, Journal of Medicinal Chemistry, vol.51, issue.19, pp.6150-6159, 2008.
DOI : 10.1021/jm8006432

E. A. Fordyce, A. J. Morrison, R. D. Sharp, and R. M. Paton, Microwave-induced generation and reactions of nitrile sulfides: an improved method for the synthesis of isothiazoles and 1,2,4-thiadiazoles, Tetrahedron, vol.2010, issue.35, pp.7192-7197

F. Roelens, N. Heldring, W. Dhooge, M. Bengtsson, F. Comhaire et al., Subtle Side-Chain Modifications of the Hop Phytoestrogen 8-Prenylnaringenin Result in Distinct Agonist/Antagonist Activity Profiles for Estrogen Receptors ? and ?, Journal of Medicinal Chemistry, vol.49, issue.25, pp.7357-7365, 2006.

W. Zhang, Z. Luo, C. H. Chen, and D. P. Curran, Solution-Phase Preparation of a 560-Compound Library of Individual Pure Mappicine Analogues by Fluorous Mixture Synthesis, Journal of the American Chemical Society, vol.124, issue.35, pp.10443-10450, 2002.

T. T. Le, N. T. Chau, T. T. Nguyen, J. Brien, T. T. Thai et al., Evidence for a Trianion Intermediate in the Metalation of 4-Hydroxy-6,7-dimethoxy-8-methyl-2-naphthoic Acid, Methodology and Application

, 5?-Didesisopropyl-5,5?-dialkylapogossypol Derivatives, The Journal of Organic Chemistry, vol.5, issue.2, pp.601-608, 2010.

D. L. Boger, T. Honda, and Q. Dang, Total Synthesis of Bleomycin A2 and Related Agents. 2. Synthesis of (-)-Pyrimidoblamic Acid, epi-(+)-Pyrimidoblamic Acid, (+)Desacetamidopyrimidoblamic Acid, and (-)-Descarboxamidopyrimidoblamic Acid, Journal of the American Chemical Society, vol.116, issue.13, pp.5619-5630, 1994.

T. Ladduwahetty, R. Baker, M. A. Cascieri, M. S. Chambers, K. Haworth et al., N-Heteroaryl-2-phenyl-3-(benzyloxy)piperidines: A Novel Class of Potent Orally Active Human NK1 Antagonists, Journal of Medicinal Chemistry, vol.39, issue.15, pp.2907-2914, 1996.

R. K. Howe, T. A. Gruner, L. G. Carter, L. L. Black, and J. E. Franz, Cycloaddition reactions of nitrile sulfides with acetylenic esters, Synthesis of isothiazolecarboxylates. The Journal of Organic Chemistry, vol.43, issue.19, pp.3736-3742, 1978.

A. M. Damas, R. O. Gould, M. M. Harding, R. M. Paton, J. F. Ross et al., Nitrile sulphides. Part 1. 1,3-Dipolar cycloaddition to carbonyl groups activated by trihaloalkyl substituents; synthesis and crystal structure of 1,3,4-oxathiazoles, Journal of the Chemical Society, vol.1, pp.2991-2995, 1981.

E. U. Roberts, H. U. Rosen, S. U. Brown, M. A. Guerrero, and X. U. Peng, US), P. R. Novel modulators of sphingosine phosphate receptors, 2009.