Deel 1: Onderzoeksproject
1. Koul, A., Arnoult, E., Lounis, N., Guillemont, J. & Andries, K. The challenge of new drug discovery for tuberculosis. Nature 469, 483-490 (2011).
2. Ducati, R. G., Ruffino-Netto, A., Basso, L. A. & Santos, D. S. The resumption of consumption -- a review on tuberculosis. Mem Inst Oswaldo Cruz 101, 697-714 (2006).
3. Dye, C. & Williams, B. G. The population dynamics and control of tuberculosis. Science 328, 856-61.
4. WHO. The Global Plan to Stop TB 2011-2015: Transforming the Fight Towards Elimination of Tuberculosis (World Health Organisation, 2010).
5. Zumla, A. et al. Viewpoint: Scientific dogmas, paradoxes and mysteries of latent Mycobacterium tuberculosis infection. Trop Med Int Health 16, 79-83.
6. Chao, M. C. & Rubin, E. J. Letting sleeping dos lie: does dormancy play a role in tuberculosis? Annu Rev Microbiol 64, 293-311.
7. Cole, S. T. (ed.) Tuberculosis and the tubercle bacillus (ASM press, 2005).
8. Wayne, L. G. & Sohaskey, C. D. Nonreplicating persistence of mycobacterium tuberculosis. Annu Rev Microbiol 55, 139-63 (2001).
9. Handbook of anti-tuberculosis agents. Tuberculosis 88, 85-170 (2008).
10. Beresford, B. & Sadoff, J. C. Update on research and development pipeline: tuberculosis vaccines. Clin Infect Dis 50 Suppl 3, S178-83.
11. Chambers, H. F. et al. Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis? Antimicrob Agents Chemother 39, 2620-4 (1995).
12. Hugonnet, J. E., Tremblay, L. W., Boshoff, H. I., Barry, C. E., 3rd & Blanchard, J. S. Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis. Science 323, 1215-8 (2009).
13. Payne, D. J., Gwynn, M. N., Holmes, D. J. & Pompliano, D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov 6, 29-40 (2007).
14. Murzin, A. G. Biochemistry. DNA building block reinvented. Science 297, 61-2 (2002).
15. Myllykallio, H. et al. An alternative flavin-dependent mechanism for thymidylate synthesis. Science 297, 105-7 (2002).
16. Koehn, E. M. & Kohen, A. Flavin-dependent thymidylate synthase: a novel pathway towards thymine. Arch Biochem Biophys 493, 96-102.
17. Sassetti, C. M. & Rubin, E. J. Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci U S A 100, 12989-94 (2003).
18. Sassetti, C. M., Boyd, D. H. & Rubin, E. J. Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48, 77-84 (2003).
19. Koehn, E. M. et al. An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene. Nature 458, 919-23 (2009).
20. Hunter, J. H., Gujjar, R., Pang, C. K. & Rathod, P. K. Kinetics and ligand-binding preferences of Mycobacterium tuberculosis thymidylate synthases, ThyA and ThyX. PLoS One 3, e2237 (2008).
21. Wang, Z. et al. Oxidase activity of a flavin-dependent thymidylate synthase. Febs J 276, 2801-10 (2009).
22. Sampathkumar, P., Turley, S., Sibley, C. H. & Hol, W. G. NADP+ expels both the co-factor and a substrate analog from the Mycobacterium tuberculosis ThyX active site: opportunities for anti-bacterial drug design. J Mol Biol 360, 1-6 (2006).
23. Napper, A. D. et al. Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. Journal of Medicinal Chemistry 48, 8045-8054 (2005).
24. Mooradian, A., Dupont, P. E., Hlavec, A. G., Aceto, M. D. & Pearl, J. 3-Aminotetrahydrocarbazoles as a new series of central nervous system agents. J Med Chem 20, 487-92 (1977).
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27. Gribble, G. W. Recent developments in indole ring synthesis-methodology and applications. Journal of the Chemical Society-Perkin Transactions 1, 1045-1075 (2000).
28. Campaigne, E. & Lake, R. D. Synthesis of Tetrahydrocarbazoles and Carbazoles by the Bischler Reaction. Journal of Organic Chemistry 24, 478-487 (1959).
29. Robinson, B. The Fisher Indole Synthesis (Wiley-Interscience, New York, 1982).
30. Liu, H. J. et al. A modified Robinson annulation process to alpha,alpha-disubstituted-beta,gamma-unsaturated cyclohexanone system. Application to the total synthesis of nanaimoal. Tetrahedron 59, 1209-1226 (2003).
31. Sampathkumar, P. et al. Structure of the Mycobacterium tuberculosis flavin dependent thymidylate synthase (MtbThyX) at 2.0A resolution. J Mol Biol 352, 1091-104 (2005).
32. Chen, J. & Hu, Y. Z. Microwave-assisted one-pot synthesis of 1,2,3,4-tetrahydrocarbazoles. Synthetic Communications 36, 1485-1494 (2006).
33. Vara, Y. et al. Regiochemistry of the microwave-assisted reaction between aromatic amines and alpha-bromoketones to yield substituted 1H-indoles. Organic & Biomolecular Chemistry 6, 1763-1772 (2008).
34. Sridharan, V., Perumal, S., Avendano, C. & Menendez, J. C. Microwave-assisted, solvent-free bischler indole synthesis. Synlett, 91-95 (2006).
35. Trujillo, J. I. et al. Novel tetrahydro-beta-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorganic & Medicinal Chemistry Letters 17, 4657-4663 (2007).
36. Sanchez-Larios, E., Holmes, J. M., Daschner, C. L. & Gravel, M. NHC-Catalyzed Spiro Bis-Indane Formation via Domino Stetter-Aldol-Michael and Stetter-Aldol-Aldol Reactions. Organic Letters 12, 5772-5775 (2010).
37. Baldur Föhlisch, R. H., Elisabeth Wolf, John J. Stezowski, Emil Eckle. Synthese von 3-Oxo-8-oxabicyclo[3.2.1]oct-6-en-2-carbonitrilen aus γ-Brom-β-oxonitrillen und Furan via [4+3]-cycloaddition von 1-Cyanallylium-2-olaten. Chem. Ber. 115, 355-380 (1982).
38. Lomax, M. I. & Greenberg, G. R. A new assay of thymidylate synthetase activity based on the release of tritium from deoxyuridylate-5-3-H. J Biol Chem 242, 109-13 (1967).
Deel 2: Literatuurstudie en onderzoeksvoorstel
1. Murzin, A. G. Biochemistry. DNA building block reinvented. Science 297, 61-2 (2002).
2. Myllykallio, H. et al. An alternative flavin-dependent mechanism for thymidylate synthesis. Science 297, 105-7 (2002).
3. Koehn, E. M. & Kohen, A. Flavin-dependent thymidylate synthase: a novel pathway towards thymine. Arch Biochem Biophys 493, 96-102.
4. Sassetti, C. M., Boyd, D. H. & Rubin, E. J. Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48, 77-84 (2003).
5. Sassetti, C. M. & Rubin, E. J. Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci U S A 100, 12989-94 (2003).
6. Hunter, J. H., Gujjar, R., Pang, C. K. & Rathod, P. K. Kinetics and ligand-binding preferences of Mycobacterium tuberculosis thymidylate synthases, ThyA and ThyX. PLoS One 3, e2237 (2008).
7. Koehn, E. M. et al. An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene. Nature 458, 919-23 (2009).
8. Ducati, R. G., Ruffino-Netto, A., Basso, L. A. & Santos, D. S. The resumption of consumption -- a review on tuberculosis. Mem Inst Oswaldo Cruz 101, 697-714 (2006).
9. WHO. The Global Plan to Stop TB 2011-2015: Transforming the Fight Towards Elimination of Tuberculosis (World Health Organisation, 2010).
10. Koul, A., Arnoult, E., Lounis, N., Guillemont, J. & Andries, K. The challenge of new drug discovery for tuberculosis. Nature 469, 483-90 (2011).
11. Sampathkumar, P. et al. Structure of the Mycobacterium tuberculosis flavin dependent thymidylate synthase (MtbThyX) at 2.0A resolution. J Mol Biol 352, 1091-104 (2005).
12. Herdewijn, P. et al. Synthesis and Evaluation of 5-Substituted 2 '-deoxyuridine Monophosphate Analogues As Inhibitors of Flavin-Dependent Thymidylate Synthase in Mycobacterium tuberculosis. Journal of Medicinal Chemistry 54, 4847-4862 (2011).
13. Martin Kögler, R. B., Steven De Jonghe, Jef Rozenski, Kristien Van Belle, Thierry Louat, Piet Herdewijn. Synthesis and evaluation of 6-aza-2'-deoxyuridine monophosphate analogues as inhibitors of thymidylate synthases in Mycobacterium tuberculosis. currently unpublished.
14. Napper, A. D. et al. Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. Journal of Medicinal Chemistry 48, 8045-8054 (2005).
15. Vara, Y. et al. Regiochemistry of the microwave-assisted reaction between aromatic amines and alpha-bromoketones to yield substituted 1H-indoles. Organic & Biomolecular Chemistry 6, 1763-1772 (2008).
16. Trujillo, J. I. et al. Novel tetrahydro-beta-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem Lett 17, 4657-63 (2007).
17. Chen, J. & Hu, Y. Z. Microwave-assisted one-pot synthesis of 1,2,3,4-tetrahydrocarbazoles. Synthetic Communications 36, 1485-1494 (2006).
18. CEM Focused MicrowaveTM Synthesis Sestem, Model Discover. User Manual.
19. Deppe H., B. A., Metz G., Erb M. (ed. Organisation, W. I. P.) (Santhera Pharmaceuticals (Schweiz) AG (Hammerstrasse 47, 4410 Liestal, CH), 2008).
20. Caner, H., Groner, E., Levy, L. & Agranat, I. Trends in the development of chiral drugs. Drug Discov Today 9, 105-10 (2004).
21. Robinson, B. The Fisher Indole Synthesis (Wiley-Interscience, New York, 1982).
22. Humphrey, G. R. & Kuethe, J. T. Practical methodologies for the synthesis of indoles. Chemical Reviews 106, 2875-2911 (2006).
23. Gribble, G. W. Recent developments in indole ring synthesis-methodology and applications. Journal of the Chemical Society-Perkin Transactions 1, 1045-1075 (2000).
24. Fischer, E. & Jourdan, F. Ueber die Hydrazine der Brenztraubensaüre. Berichte der deutschen chemischen Gesellschaft 16, 2241–2245 (1883).
25. Stadlbauer, W., Van Dang, H. & Berger, B. S. Synthesis and Reactions of 4-Hydroxy-8,9,10,11-tetrahydropyrido[3,2, 1-jk]carbazol-6-ones. Journal of Heterocyclic Chemistry 47, 807-824 (2010).
26. Li, L. H. et al. Potent and highly selective DP1 antagonists with 2,3,4,9-tetrahydro-1H-carbazole as pharmacophore. Bioorganic & Medicinal Chemistry Letters 20, 7462-7465 (2010).
27. Gu, W. & Wang, S. F. Synthesis and antimicrobial activities of novel 1H-dibenzo[a,c]carbazoles from dehydroabietic acid. European Journal of Medicinal Chemistry 45, 4692-4696 (2010).
28. Gudmundsson, K. S. et al. Substituted tetrahydrocarbazoles with potent activity against human papillomaviruses. Bioorganic & Medicinal Chemistry Letters 19, 3489-3492 (2009).
29. Lipinska, T. M. & Czarnocki, S. J. A new approach to difficult Fischer synthesis: The use of zinc chloride catalyst in triethylene glycol under controlled microwave irradiation. Organic Letters 8, 367-370 (2006).
30. Buchwald, S. L. & Chae, J. Y. Palladium-catalyzed regioselective hydrodebromination of dibromoindoles: Application to the enantioselective synthesis of indolodioxane U86192A. Journal of Organic Chemistry 69, 3336-3339 (2004).
31. Buchwald, S. L., Wagaw, S. & Yang, B. H. A palladium-catalyzed strategy for the preparation of indoles: A novel entry into the Fischer indole synthesis. Journal of the American Chemical Society 120, 6621-6622 (1998).
32. Buchwald, S. L., Wagaw, S. & Yang, B. H. A palladium-catalyzed method for the preparation of indoles via the Fischer indole synthesis. Journal of the American Chemical Society 121, 10251-10263 (1999).
33. Diederich, F. & Lustenberger, P. Towards asymmetric catalysis in the major groove of 1,1 '-binaphthalenes. Helvetica Chimica Acta 83, 2865-2883 (2000).
34. Yagi, S., Kitayama, H. & Takagishi, T. Synthesis of a novel tweezers-type host aiming at chiral discrimination by circular dichroism spectroscopy. Journal of the Chemical Society-Perkin Transactions 1, 925-932 (2000).
35. Cacchi, S. & Fabrizi, G. Synthesis and functionalization of Indoles through palladium-catalyzed reactions. Chemical Reviews 105, 2873-2920 (2005).
36. Bhanage, B. M., Sawant, D. N., Wagh, Y. S., Tambade, P. J. & Bhatte, K. D. Cyanides-Free Cyanation of Aryl Halides using Formamide. Advanced Synthesis & Catalysis 353, 781-787 (2011).
37. Vilar, R. et al. Rapid carbonylative coupling reactions using palladium(I) dimers: applications to (11)CO-radiolabelling for the synthesis of PET tracers. Organic & Biomolecular Chemistry 9, 3499-3503 (2011).
38. Lloyd-Williams, P. et al. Arylboronic acids and arylpinacolboronate esters in Suzuki coupling reactions involving indoles. Partner role swapping and heterocycle protection. Journal of Organic Chemistry 69, 6812-6820 (2004).
39. Sonogashira, K., Tohda, Y. & Hagihara, N. Convenient Synthesis of Acetylenes - Catalytic Substitutions of Acetylenic Hydrogen with Bromoalkenes, Iodoarenes, and Bromopyridines. Tetrahedron Letters, 4467-4470 (1975).
40. Sakamoto, T., Nagano, T., Kondo, Y. & Yamanaka, H. Palladium-Catalyzed Coupling Reaction of 3-Iodoindoles and 3-Iodobenzo[B]Thiophene with Terminal Acetylenes. Chemical & Pharmaceutical Bulletin 36, 2248-2252 (1988).
41. de Kloe, G. E., Bailey, D., Leurs, R. & de Esch, I. J. P. Transforming fragments into candidates: small becomes big in medicinal chemistry. Drug Discovery Today 14, 630-646 (2009).
42. Bembenek, S. D., Tounge, B. A. & Reynolds, C. H. Ligand efficiency and fragment-based drug discovery. Drug Discovery Today 14, 278-283 (2009).
43. Zhao, H. Y. Scaffold selection and scaffold hopping in lead generation: a medicinal chemistry perspective. Drug Discovery Today 12, 149-155 (2007).
44. Böhm, H.-J., Flohr, A. & Stahl, M. Scaffold hopping. Drug Discov Today: Technologies 1, 217-224 (2004).
45. Shishido, Y. et al. Synthesis of benzamide derivatives as TRPV1 antagonists. Bioorganic & Medicinal Chemistry Letters 18, 1072-1078 (2008).