Structure-Based Design of Inhibitors of Purine Nucleoside Phosphorylase. 1. 9-(Arylmethyl) Derivatives of 9-Deazaguanine

Journal of Medicinal Chemistry

Volumn 36, Issue 1, 1993, Pages 55-69

  Montgomery, John A ^a,b   Niwas, Shri ^b   Rose, Jerry D ^b   Secrist, John A ^b   Babu, Y Sudhakar ^a   Bugg, Charles E ^c   Erion, Mark D ^d,e   Guida, Wayne C ^d   Ealick, Steven E ^c,f  

^a BIOCRYST PHARMACEUTICALS INC   (United States)

^b SOUTHERN RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^d NOVARTIS PHARMA AG   (Switzerland)

^e Gensia Inc   (United States)

^f Department of Obstetrics Gynecology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

9 (3,4 DICHLOROBENZYL) 9 DEAZAGUANINE; 9 DEAZAGUANINE DERIVATIVE; DEOXYRIBONUCLEOSIDE; ENZYME INHIBITOR; PURINE NUCLEOSIDE PHOSPHORYLASE; UNCLASSIFIED DRUG;

ARTICLE; COMPUTER GRAPHICS; DRUG DESIGN; DRUG POTENCY; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME INHIBITOR INTERACTION; ENZYME STRUCTURE; HYDROGEN BOND; PRIORITY JOURNAL; PURINE METABOLISM; STRUCTURE ACTIVITY RELATION; SYSTEM ANALYSIS; X RAY CRYSTALLOGRAPHY;

ANIMAL; BINDING SITES; CATTLE; COMPARATIVE STUDY; CRYSTALLOGRAPHY; ENZYME INHIBITORS; GUANINE; KINETICS; PURINE-NUCLEOSIDE PHOSPHORYLASE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0027458426     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00053a008     Document Type: Article

References (67)

1. 2 Symmetric Inhibitor Completed to HIV-1 Protease. Science 1990, 249, 527–533.
2. Appelt, K.; Bacquet, R. J.; Bartlett, C. A.; Booth, C. L. J.; Freer, S. T.; Fuhry, M. A. M.; Gehring, M. R.; Herrmann, S. M.; Howland, E. F.; Janson, C. A.; Jones, T. R.; Kan, C.-C.; Kathardekar, V.; Lewis, K. K.; Marzoni, G. P.; Matthews, D. A.; Mohr, C.; Moomaw, E. W.; Morse, C. A.; Oatley, S. J.; Ogden, R. C.; Reddy, M. R.; Reich, S. H.; Schoettlin, W. S.; Smith, W. W.; Varney, M. D.; Villafranca, J. E.; Ward, R. W.; Webber, S.; Webber, S. E.; Welsh, K. M.; White, J. Design of Enzyme Inhibitors Using Iterative Protein Crystallographic Analysis. J. Med. Chem. 1991, 34, 1925–1934.
3. For a preliminary account of our work, see Ealick, S. E.; Babu, Y. S.; Bugg, C. E.; Erion, M. D.; Guida, W. C.; Montgomery, J. A.; Secrist, J. A., III. Application of Crystallographic and Modeling Methods in the Design of Purine Nucleoside Phosphorylase Inhibitors. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 11540–11544.
4. McCammon, J. A.; Harvey, S. C. Dynamics of Proteins and Nucleic Acids; Cambridge Univ.: New York, 1987.
5. Van Gunsteren, W. F.; Weiner, P. K., Eds. Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications; Escom Science: The Netherlands, 1989.
6. DesJarlais, R. L.; Sheridan, R. P.; Dixon, J. S.; Kuntz, I. D.; Venkataraghavan, R. Docking Flexible Ligands to Macromolecular Receptors by Molecular Shape. J. Med. Chem. 1986, 29, 2149.
7. Hart, T.; Read, R. J. A Multiple-Start Monte Carlo Docking Method. Proteins. 1992, 13, 206–222.
8. Caflisch, A.; Neiderer, P.; Anliker, M. Monte Carlo Docking of Oligopeptides to Proteins. Proteins. 1992, 13, 223–230.
9. Meng, E. C.; Shoichet, B. K.; Kuntz, I. D. Automated Docking with Grid-Based Energy Evaluation. J. Comput. Chem. 1992, 13, 505–524.
10. Leach, A. R.; Kuntz, I. D. Conformational Analysis of Flexible Ligands in Macromolecular Receptor Sites. J. Comput. Chem. 1992, 13, 730–748.
11. Guida, W. C.; Bohacek, R. S.; Erion, M. D. Probing the Conformational Space Available to Inhibitors in the Thermolysin Active Site Using Monte Carlo/Energy Minimization Techniques. J. Comput. Chem. 1992, 13, 214–228.
12. Kim, B. K.; Cha, S.; Parks, R. E., Jr. Purine Nucleoside Phosphorylase from Human Erythrocytes. J. Biol. Chem. 1968, 243, 1763–1770.
13. Zannis, V.; Doyle, D.; Martin, D. W., Jr. Purification and Characterization of Human Erythrocyte Purine Nucleoside Phosphorylase and Its Subunits. J. Biol. Chem. 1978, 253 504–510.
14. Ghangas, G.; Reem, G. H. Characterization of the Subunit Structure of Human Placental Nucleoside Phosphorylase by Immunochemistry. J. Biol. Chem. 1979, 254, 4233–4237.
15. Wiginton, D. A.; Coleman, M. S.; Hutton, J. J. Characterization of Purine Nucleoside Phosphorylase from Human Granulocytes and Its Metabolism of Deoxyribonucleosides. J. Biol. Chem. 1980, 255 6663–6669.
16. Price, V. E.; Otey, M. C.; Plesner, P. Preparation of Nucleoside Phosphorylase from Calf Spleen. Methods Enzymol. 1955, 2 448–453.
17. Lewis, A. S.; Glantz, M. D. Bovine Brain Purine-Nucleoside Phosphorylase Purification, Characterization, and Catalytic Mechanism. Biochemistry 1976, 15, 4451–4457.
18. Lewis, A. S.; Glantz, M. D. Monomeric Purine Nucleoside Phosphorylase from Rabbit Liver. J. Biol. Chem. 1976, 257 407–413.
19. Murakami, K.; Mitsui, A.; Tsushima, K. Purine Nucleoside Phosphorylase of Chicken Liver. Biochim. Biophys. Acta. 1971, 235, 99–105.
20. Murakami, K.; Tsushima, K. Crystallization and Some Properties of Purine Nucleoside Phosphorylase From Chicken Liver. Biochim. Biophys. Acta. 1975, 384, 390–398.
21. Jensen, K. F.; Nygaard, P. Purine Nucleoside Phosphorylase from Escherichia coli and Salmonella typhimurium. Eur. J. Biochem. 1975, 57 253–265.
22. Schimandle, C. M.; Tanigoshi, L.; Mole, L. A.; Sherman, I. W. Purine Nucleoside Phosphorylase of the Malarial Parasite, Plasmodium lophurae. J. Biol. Chem. 1985, 260, 4455–4460.
23. Edwards, Y. H.; Edwards, P. A.; Hopkinson, D. A. A Trimeric Structure for Mammalian Purine Nucleoside Phosphorylase. FEBS Lett. 1973, 32, 235–237.
24. Ikezawa, Z.; Nishino, T.; Murakami, K.; Tsushima, K. Purine Nucleoside Phosphorylase from Bovine Liver. Comp. Biochem. Physiol. B: Comp. Biochem. 1978, 60B, 111–116.
25. Murakami, K.; Tsushima, K. Molecular Properties and a Nonidentical Trimeric Structure of Purine Nucleoside Phosphorylase From Chicken Liver. Biochim. Biophys. Acta. 1976, 453, 205–210.
26. Ward, R. D.; McAndrew, B. J.; Wallis, G. P. Purine Nucleoside Phosphorylase Variation in the Brook Lamprey, Lampetra planeri.(Bloch) (Petromyzone, Agnatha): Evidence for a Trimeric Enzyme Structure. Biochem. Genet. 1979, 17, 251–256.
27. Savage, B.; Spencer, N. Partial Purification and Properties of Purine Nucleoside Phosphorylase from Rabbit Erythrocytes. Biochem. J. 1977, 167, 703–710.
28. Agarwal, R. P.; Parks, R. E., Jr. Purine Nucleoside Phosphorylase from Human Erythrocytes. J. Biol. Chem. 1969, 244, 644–647.
29. Stoeckler, J. D.; Agarwal, R. P.; Agarwal, K. C.; Schmid, K.; Parks, R. E., Jr. Purine Nucleoside Phosphorylase from Human Erythrocytes: Physicochemical Properties of the Crystalline Enzyme. Biochemistry 1978, 17, 278–283.
30. Lewis, A. S.; Lowy, B. A. Human Erythrocyte Purine Nucleoside Phosphorylase: Molecular Weight and Physical Properties. J. Biol. Chem. 1979, 254 9927–9932.
31. Williams, S. R.; Goddard, J. M.; Martin, D. W., Jr. Human Purine Nucleoside Phosphorylase cDNA Sequence and Genomic Clone Characterization. Nucleic Acids Res. 1984, 12, 5779–5787.
32. Giblett, E. R.; Ammann, A. J.; Wara, D. W.; Sandman, R.; Diamond, L. K. Nucleoside-Phosphorylase Deficiency in a Child With Severely Defective T-Cell Immunity and Normal B-Cell Immunity. Lancet. 1975, I, 1010–1013.
33. Stoop, J. W.; Zegers, B. J. M.; Hendricks, G. F. M.; Siegenbeek van Heukelom, L. H.; Staal, G. E. J.; de Bree, P. K.; Wadman, S. K.; Ballieux, R. E. Purine Nucleoside Phosphorylase Deficiency Associated With Selective Cellular Immunodeficiency. N. Engl. J. Med. 1977, 296 651–655.
34. Rich, K. C.; Arnold, W. J.; Palella, T.; Fox, I. H. Cellular Immune Deficiency With Autoimmune Hemolytic Anemia in Purine Nucleoside Phosphorylase Deficiency. Am. J. Med. 1979, 67, 172–176.
35. Stoeckler, J. D.; Ealick, S. E.; Bugg, C. E.; Parks, R. E., Jr. Design of Purine Nucleoside Phosphorylase Inhibitors. Fed. Proc. 1986, 45, 2773–2778.
36. Stoeckler, J. D. Purine Nucleoside Phosphorylase: A Target for Chemotherapy. In Developments in Cancer Chemotherapy; Glazer, R. I., Ed.; CRC Press: Boca Raton, 1984; pp 35–60.
37. Sircar, J. C.; Gilbertsen, R. B. Purine Nucleoside Phosphorylase (PNP) Inhibitors: Potentially Selective Immunosuppressive Agents. Drugs Future. 1988, 13, 653–668.
38. Ealick, S. E.; Rule, S. A.; Carter, D. C.; Greenhough, T. J.; Babu, Y. S.; Cook, W. J.; Habash, J.; Helliwell, J. R.; Stoeckler, J. D.; Parks, R. E., Jr.; Chen, S.-F.; Bugg, C. E. Three-dimensional Structure of Human Erythrocytic Purine Nucleoside Phosphorylase at 3.2 Å Resolution. J. Biol. Chem. 1990, 265, 1812–1820.
39. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. Macro-Model — An Integrated Software System for Modeling Organic and Bioorganic Molecules Using Molecular Mechanics. J. Comput. Chem. 1990, 11, 440–467.
40. Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta, S., Jr.; Weiner, P. A New Force Field for Molecular Mechanical Simulation of Nucleic Acids and Proteins. J. Am. Chem. Soc. 1984, 106, 765–784.
41. Weiner, S. J.; Kollman, P. A.; Nguyen, D. T.; Case, D. A. An All Atom Force Field for Simulations of Proteins and Nucleic Acids. J. Comput. Chem. 1986, 7 230–252.
42. Chang, G.; Guida, W. C.; Still, W. C. An Internal Coordinate Monte Carlo Method for Searching Conformational Space. J. Am. Chem. Soc. 1989, 111, 4379–4386.
43. Tuttle, J. V.; Krenitsky, T. A. Effects of Acyclovir and Its Metabolites on Purine Nucleoside Phosphorylase. J. Biol. Chem. 1984, 259 4065–4069.
44. Stoeckler, J. D.; Cambor, C.; Kuhns, V.; Chu, S.-H.; Parks, R. E., Jr. Inhibitors of Purine Nucleoside Phosphorylase. Biochem. Pharmacol. 1982, 31, 163–171.
45. Shewach, D. S.; Chem, J.-W.; Pillote, K. E.; Townsend, L. B.; Daddona, P. E. Potentiation of 2′ Deoxyguanosine Cytotoxicity by a Novel Inhibitor of Purine Nucleoside Phosphorylase, 8-Amino-9-benzylguanine. Cancer Res. 1986, 46, 519–523.
46. Stoeckler, J. D.; Ryden, J. B.; Parks, R. E., Jr.; Chu, M.-Y.; Lim, M.-L.; Ren, W.-Y.; Klein, R. S. Inhibitors of Purine Nucleoside Phosphorylase: Effects of 9-Deazapurine Ribonucleosides and Synthesis of 5′-Deoxy-5′-iodo-9-deazainosine. Cancer Res. 1986, 46, 1774–1778.
47. Halazy, S.; Ehrhard, A.; Danzin, C. 9-(Difluorophosphonoalkyl)-guanines as a New Class of Multisubstrate Analogue Inhibitors of Purine Nucleoside Phosphorylase. J. Am. Chem. Soc. 1991, 113, 315–317.
48. Mamont, P. S.; Weibel, M.; Danzin, C.; Halazy, S. Effects of 9-(Difluorophosphonoalkyl)guanines, A New Class of Multisubstrate Analogue Inhibitors of Purine Nucleoside Phosphorylase in Cultured Human Leukemic Lymphoblast Molt-4 Cells. Int. J. Purine Pyrimidine Res. 1991, 2 (Suppl. 1), 62.
49. Lim, M. I.; Klein, R. S.; Fox, J. J. A New Synthesis of Pyrrolo-[3,2-d pyrimidines (“9-Deazapurines”) Via 3-Amino-2-carboalkoxypyrroles. J. Org. Chem. 1979, 44, 3826–3829.
50. Lim, M.-I.; Klein, R. S.; Fox, J. J. Synthesis of the Pyrrolo[3,2-d pyrimidine C Nucleoside Isostere of Inosine. Tetrahedron Lett. 1980, 21, 1013–1016.
51. Lim, M.-I.; Ren, W.-Y.; Otter, B. A.; Klein, R. S. Synthesis of “9-Deazaguanosine” and Other New Pyrrolo[3,2-d pyrimidine C-Nucleosides. J. Org. Chem. 1983, 48, 780–788.
52. Netherlands Patent 6,610,204, 1967
53. New Cyclic Thioimidates. Chem. Abstr. 1968, 68, 39631K.
54. Profitt, J. A.; Watt, D. S.; Corey, E. J. A Reagent for the α,β Reduction of Conjugated Nitriles. J. Org. Chem. 1975, 40, 127–128.
55. U.S. Patent 4,279,903, 1981.
56. Skorcz, J. A.; Suh, J. T.; Judd, C. I.; Finkelstein, M.; Conway, A. C. Benzocyclobutene Derivatives. Oximes With Muscle Relaxant Characteristics. J. Med. Chem. 1966, 9, 656–659.
57. Anderson, E. L.; Casey, J. E., Jr.; Greene, L. C.; Lafferty, J. J.; Reiff, H. E. Synthesis and Muscle Relaxant Properties of 3-Amino-4-arylpyrazoles. J. Med. Chem. 1964, 7 259–268.
58. Lim, M. I.; Klein, R. S. Synthesis of “9-Deazaadenosine”, A New Cytotoxic C-Nucleoside Isostere of Adenosine. Tetrahedron Lett. 1981, 22 25–28.
59. For a review, see Taylor, E. C.; McKillop, A. Chemistry of Cyclic Enaminonitriles and O-Aminonitriles. Adv. Org. Chem. 1970, 7 272.
60. Yamazaki, A.; Okutsu, M. Cyclization of 5-Amino-1-β D-ribofuranosylimidazole-4-carboxamide (AICA-riboside): A Review. J. Heterocycl. Chem. 1978, 15, 353–358.
61. Lewis, A. F.; Townsend, L. B. Pyrazolopyrimidine Nucleosides. 13. Synthesis of the Novel C-Nucleoside 5-Amino-3-(β D-ribofuranosyl)pyrazolo[4,3-d pyrimidin-7-one, a Guanosine Analogue Related to the Nucleoside Antibiotic Formycin B. J. Am. Chem. Soc. 1982, 104, 1073–1077.
62. Burley, S. K.; Petsko, G. A. Aromatic-Aromatic Interaction: A Mechanism of Protein Structure Stabilization. Science 1985, 229, 23–28.
63. Casari, G.; Sippl, M. J. Structure-derived Hydrophobic Potential. Hydrophobic Potential Derived from X-ray Structures of Globular Proteins is able to Identify Native Folds. J. Mol. Biol. 1992, 224, 725–732.
64. Still, W. C.; Kahn, M.; Mitra, A. Rapid Chromatographic Technique for Preparative Separations With Moderate Resolution. J. Org. Chem. 1978, 43, 2923–2925.
65. Stoeckler, J. D.; Parks, R. E., Jr. Purine Nucleoside Phosphorylase. Methods Pharmacol. 1985, 6 147–162.
66. Bernstein, F. C.; Koetzle, T. F.; Williams, G. J. B.; Meyer, E. F., Jr.; Brice, M. D.; Rodgers, J. R.; Kennard, O.; Shimanouchi, T.; Tasumi, M. The Protein Data Bank: A Computer-based Archival File for Macromolecular Structures. J. Mol. Biol. 1977, 112, 535–542.
67. Bohacek, R. S.; McMartin, C. M. Definition and Display of Steric, Hydrophobic, and Hydrogen-Bonding Properties of Ligand Binding Sites in Proteins Using Lee and Richards Accessible Surface: Validation of a High-Resolution Graphical Tool for Drug Design. J. Med. Chem. 1992, 35, 1671–1684.