Discovery of 5-substituted-6-chlorouracils as efficient inhibitors of human thymidine phosphorylase

Journal of Medicinal Chemistry

Volumn 50, Issue 24, 2007, Pages 6016-6023

  Nencka, Radim ^a   Votruba, Ivan ^a   Hřebabecký, Hubert ^a   Jansa, Petr ^a   Tloušt'ová, Eva ^a   Horská, Květa ^a   Masojídková, Milena ^a   Holý, Antonín ^a  

^a INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY   (Czech Republic)

Author keywords

[No Author keywords available]

Indexed keywords

6 CHLORO 5 CYCLOPENT 1 EN 1 YLURACIL; CHLORINE DERIVATIVE; CYCLOPENTANE; HALOGEN; THYMIDINE PHOSPHORYLASE; UNCLASSIFIED DRUG; URACIL DERIVATIVE;

ANGIOGENESIS; ANIMAL CELL; ARTICLE; CELL STRAIN V 79; DRUG POTENCY; DRUG SCREENING; ENZYME INHIBITION; ENZYME PURIFICATION; HYDROPHOBICITY; NONHUMAN; PLACENTA; PROTEIN EXPRESSION;

ANGIOGENESIS INHIBITORS; HUMANS; KINETICS; MODELS, MOLECULAR; STRUCTURE-ACTIVITY RELATIONSHIP; THYMIDINE PHOSPHORYLASE; URACIL;

EID: 37849015917     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070644i     Document Type: Article

References (36)

1. Bouïs, D.; Kusumanto, Y.; Meijer, C.; Mulder, N. H.; Hospers, G. A. P. A Review on Pro- and Anti-Angiogenic Factors as Targets of Clinical Intervention. Pharmacol. Res. 2006, 53, 89-103.
2. Tabruyn, S. P.; Griffioen, A. W. Molecular Pathways of Angiogenesis Inhibition. Biochem. Biophys. Res. Commun. 2007, 355, 1-5.
3. Moghaddam, A.; Zhang, H.; Fan, T. D.; Hu, D.; Lees, V. C.; Turley, H.; Fox, S. B.; Gatter, K. C.; Harris, A. L.; Bicknell, R. Thymidine Phosphorylase is Angiogenic and Promotes Tumor Growth. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 998-1002.
4. Brown, N. S.; Bicknell, R. Thymidine Phosphorylase, 2-Deoxy-D- ribose and Angiogenesis. Biochem. J. 1998, 334, 1-8.
5. Matsuura, T.; Kuratate, I.; Teramachi, K.; Osaki, M.; Fukuda, Y.; Ito, H. Thymidine Phosphorylase Expression Is Associated with Both Increase of Intratumoral Microvessels and Decrease of Apoptosis in Human Colorectal Carcinomas. Cancer Res. 1999, 59, 5037-5040.
6. Desgranges, C.; Razaka, G.; Rabaud, M.; Bricaud, H.; Balzarini, J.; De Clercq, E. Phosphorolysis of (E)-5-(2-Bromovinyl)-2′-deoxyuridine (BVDU) and Other 5-Substituted-2′-deoxyuridines by Purified Human Thymidine Phosphorylase and Intact Blood Platelets. Biochem. Pharmacol. 1983, 32, 3583-3590.
7. Nencka, R.; Votruba, I.; Hřebabecký, H.; Tloušt'ová, E.; Horská, K.; Masojídková, M.; Holý, A. Design and Synthesis of Novel 5,6-Disubstituted Uracil Derivatives as Potent Inhibitors of Thymidine Phosphorylase. Bioorg. Med. Chem. Lett. 2006, 16, 1335-1337.
8. Fukushima, M.; Suzuki, N.; Emura, T.; Yano, S.; Kazuno, H.; Tada, Y.; Yamada, Y.; Asao, T. Structure and Activity of Specific Inhibitors of Thymidine Phosphorylase To Potentiate the Function of Antitumor 2′- Deoxyribonucleosides. Biochem. Pharmacol. 2000, 59, 1227-1236.
9. Yano, S.; Kazuno, H.; Sato, T.; Suzuki, N.; Emura, T.; Konstanty, W.; Yamashita, J.; Tada, Y.; Yamada, Y.; Fukushima, M.; Asao, T. Synthesis and Evaluation of 6-Methylene-Bridged Uracil Derivatives. Part 2: Optimization of Inhibitors of Human Thymidine Phosphorylase and Their Selectivity with Uridine Phosphorylase. Bioorg. Med. Chem. 2004, 12, 3443-3450.
10. Balzarini, J.; Esteban-Gamboa, A.; Esnouf, R.; Liekens, S.; Neyts, J.; De Clercq, E.; Camarasa, M. J.; Pérez-Pérez, M. J. 7-Deazaxanthine, a Novel Prototype Inhibitor of Thymidine Phosphorylase. FEBS Lett. 1998, 438, 91-95.
11. Casanova, E.; Hernández, A. I.; Priego, E. M.; Liekens, S.; Camarasa, M. J.; Balzarini, J.; Pérez-Pérez, M. J. 5′-O-Tritylinosine and Analogues as Allosteric Inhibitors of Human Thymidine Phosphorylase. J. Med. Chem. 2006, 49, 5562-5570.
12. Allan, A. L.; Gladstone, P. L.; Price, M. L. P.; Hopkins, S. A.; Juarez, J. C.; Donate, F.; Ternansky, R. J.; Shaw, D. E.; Ganem, B.; Li, Y.; Wang, W.; Ealick, S. Synthesis and Evaluation of Multisubstrate Bicyclic Pyrimidine Nucleoside Inhibitors of Human Thymidine Phosphorylase. J. Med. Chem. 2006, 49, 7807-7815.
13. Votruba, I.; Pomeisl, K.; Tloušt'ová, E.; Holý, A.; Otová, B. Inhibition of Thymidine Phosphorylase (PD-ECGF) from SD-lymphoma by Phosphonomethoxyalkyl Thymines. Biochem. Pharmacol. 2005, 69, 1517-1521.
14. Baker, B. R.; Kawazu, M. Irreversible Enzyme Inhibitors. LXXVIII. Inhibitors of Thymidine Phosphorylase. IV. Hydrophobic Bonding by Uracils Substituted at the 5 and 6 Positions. J. Med. Chem. 1967, 10, 316-320.
15. Baker, B. R.; Rzeszotarski, W. Irreversible Enzyme Inhibitors. CXXI. Thymidine Phosphorylase. 9. Nature and Dimensions of the Hydrophobic Bonding Region. J. Med. Chem. 1968, 11, 639-644.
16. Cushman, M.; Mihalic, J. T.; Kis, K.; Bacher, A. Design, Synthesis, and Biological Evaluation of Homologous Phosphonic Acids and Sulfonic Acids as Inhibitors of Lumazine Synthase. J. Org. Chem. 1999, 64, 3838-3845.
17. Koroniak, H.; Jankowski, A.; Karasnowski, M. Facile Large Scale Synthesis of 5-Alkyluracils. Org. Prep. Proc. Int. 1993, 25, 563-568.
18. Gauri, K. K.; Pastenheimer, H. German Patent 1250829; Chem. Abstr. 1968, 68, 105226k.
19. Ple, N.; Turck, A.; Figuet, E.; Queguiner, G. Metallation of Diazines. III. New Synthesis of Analogues of Trimethoprim and of Bacimethrin. J. Heterocycl. Chem. 1991, 28, 283-287.
20. Elderfield, R. C.; Prasad, R. N. Synthesis of Potential Anticancer Agents. IV. Synthesis of Certain Substituted Amino- and Aziridinopyrimidines. J. Org. Chem. 1960, 25, 1583-1590.
21. Hendry, J. A.; Homer, R. F. New Cytotoxic Agents with Tumor-Inhibitory Activity. Part I. Some Aziridinopyrimidine Derivatives. J. Chem. Soc. 1952, 328-333.
22. Miyazono, K.; Okabe, T.; Urabe, A.; Takaku, F.; Heldin, C. H. Purification and Properties of an Endothelial Cell Growth Factor from Human Platelets. J. Biol. Chem. 1987, 262, 4098-4103.
23. Desgranges, C.; Razaka, G.; Rabaud, M.; Bricaud, H. Catabolism of Thymidine in Human Blood Platelets. Purification and Properties of Thymidine Phosphorylase. Biochim. Biophys. Acta 1981, 654, 211-218.
24. Norman, R. A.; Barry, S. T.; Bate, M.; Breed, J.; Colls, J. G.; Ernill, R. J.; Luke, R. W. A.; Minshull, C. A.; McAlister, M. S. B.; McCall, E. J.; McMiken, H. H. J.; Paterson, D. S.; Timms, D.; Tucker, J. A.; Pauptit, R. A. Crystal Structure of Human Thymidine Phosphorylase in Complex with a Small Molecule Inhibitor. Structure 2004, 12, 75-84.
25. El Omari, K.; Bronckaers, A.; Liekens, S.; Pérez-Pérez, M.-J.; Balzarini, J.; Stammers, D. K. Structural Basis for Non-Competitive Product Inhibition in Human Thymidine Phosphorylase: Implications for Drug Design. Biochem. J. 2006, 399, 199-204.
26. Pugmire, M. J.; Cook, W. J.; Jasanoff, A.; Walter, M. R.; Ealick, S. E. Structural and Theoretical Studies Suggest Domain Movement Produces an Active Conformation of Thymidine Phosphorylase. J. Mol. Biol. 1998, 281, 285-299.
27. CambridgeSoft Corp., http://www.cambridgesoft.com.
28. VCCLAB, http://www.vcclab.org/lab/alogps/.
29. Tetko, I. V.; Tanchuk, V. Yu.; Kasheva, T. N.; Villa, A. E. P. Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices. J. Chem. Inf. Comput. Sci. 2001, 41, 1488-93.
30. Serajuddin, A. T. M. Salt formation to improve drug solubility. Adv. Drug. Deliv. Rev. 2007, 59, 603-616.
31. Ertl, P.; Rohde, B.; Selzer, P. Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment Based Contributions and Its Application to the Prediction of Drug Transport Properties. J. Med. Chem. 2000, 43, 3714-3717.
32. Advanced Chemistry Development, Inc.; http://www.acdlabs.com/.
33. Scherrer, R. A.; Howard, S. M. Use of Distribution Coefficients in Quantitative Structure-Activity Relationships. J. Med. Chem. 1977, 20, 53-58.
34. Veber, D. F.; Johnson, S. R.; Cheng, H. Y.; Smith, B. R.; Ward, K. W.; Kopple, K. D. Molecular Properties That Influence the Oral Bioavailability of Drug Candidates. J. Med. Chem. 2002, 45, 2615-2623.
35. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and Computational Approaches To Estimate Solubility and Permeability in Drug Discovery and Development Settings. Adv. Drug. Delivery Rev. 2001, 46, 3-26.
36. Hou, T. J.; Wang, J. M.; Zhang, W.; Wang, W.; Xu, X. ADME Evaluation in Drug Discovery. 7. Prediction of Oral Absorption by Correlation and Classification. J. Chem. Inf. Model. 2007, 47, 208-218.