A fluorine scan of the phenylamidinium needle of tricyclic thrombin inhibitors: Effects of fluorine substitution on pKa and binding affinity and evidence for intermolecular C-F...CN interactions

Organic and Biomolecular Chemistry

Volumn 2, Issue 9, 2004, Pages 1339-1352

  Olsen, Jacob ^a   Seiler, Paul ^a   Wagner, Björn ^b   Fischer, Holger ^b   Tschopp, Thomas ^b   Obst Sander, Ulrike ^b   Banner, David W ^b   Kansy, Manfred ^b   Müller, Klaus ^b   Diederich, François ^a  

^a ETH ZURICH   (Switzerland)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING ENERGY; CORROSION INHIBITORS; CRYSTALS; FLUORINE; NEEDLES; PHARMACOKINETICS; PROTEINS; X RAY ANALYSIS;

BINDING AFFINITY; INTERMOLECULAR; PHENYLAMIDINIUM; THROMBIN INHIBITORS;

SCANNING;

AMIDINE; ANTITHROMBIN; FLUORINE; THROMBIN; TRYPSIN;

ARTICLE; BINDING COMPETITION; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; DRUG ANTAGONISM; METABOLISM; PH; STEREOISOMERISM; X RAY CRYSTALLOGRAPHY;

AMIDINES; ANTITHROMBINS; BINDING, COMPETITIVE; CRYSTALLOGRAPHY, X-RAY; FLUORINE; HYDROGEN-ION CONCENTRATION; MODELS, MOLECULAR; MOLECULAR CONFORMATION; STEREOISOMERISM; THROMBIN; TRYPSIN;

EID: 2542432021     PISSN: 14770520     EISSN: None     Source Type: Journal    
DOI: 10.1039/b402515f     Document Type: Article

References (76)

1. J. Fried and E. F. Sabo, J. Am. Chem. Soc., 1954, 76, 1455-1456.
2. F. M. D. Ismael, J. Fluorine Chem., 2002, 118, 27-33.
3. M. Schlosser, in Enantiocontrolled Synthesis of Fluoro-Organic Compounds: Stereochemical Challenges and Biomedicinal Targets, ed. V. A. Soloshonok, Wiley, Chichester, 1999, pp 613-659.
4. C. M. Weeks, W. L. Duax and M. E. Wolff, J. Am. Chem. Soc., 1973, 95, 2865-2868.
5. P. M. Matias, M. A. Carrondo, R. Coelho, M. Thomaz, X.-Y. Zhao, A. Wegg, K. Crusius, U. Egner and P. Donner, J. Med. Chem., 2002, 45, 1439-1446.
6. (a) B. K. Park, N. R. Kitteringham and P. M. O'Neill, Annu. Rev. Pharmacol. Toxicol., 2001, 41, 443-470;
7. (b) D. O'Hagan and H. S. Rzepa, Chem. Commun., 1997, 645-652;
8. (c) B. E. Smart, J. Fluorine Chem., 2001, 109, 3-11.
9. (a) U. Obst, V. Gramlich, F. Diederich, L. Weber and D. W. Banner, Angew. Chem., Int. Ed., 1995, 34, 1739-1742;
10. (b) U. Obst, D. W. Banner, L. Weber and F. Diederich, Chem. Biol., 1997, 4, 287-295;
11. (c) U. Obst, P. Betschmann, C. Lerner, P. Seiler, F. Diederich, V. Gramlich, L. Weber, D. W. Banner and P. Schönholzer, Helv. Chim. Acta, 2000, 83, 855-909;
12. (d) P. Betschmann, S. Sahli, F. Diederich, U. Obst and V. Gramlich, Helv. Chim. Acta, 2002, 85, 1210-1245.
13. B. Kuhn and P. A. Kollman, J. Am. Chem. Soc., 2000, 122, 3909-3916.
14. (a) J. A. Olsen, D. W. Banner, P. Seiler, U. Obst Sander, A. D'Arcy, M. Stihle, K. Müller and F. Diederich, Angew. Chem., Int. Ed., 2003, 42, 2507-2511;
15. (b) J. A. Olsen, D. W. Banner, P. Seiler, U. Obst-Sander, A. D'Arcy, M. Stihle, K. Müller and F. Diederich, ChemBioChem, in press.
16. (a) For examples of phenylamidinium-containing thrombin inhibitors, see: J. W. Nilsson, I. Kvarnstrom, D. Musil, I. Nilsson and B. Samulesson, J. Med. Chem., 2003, 46, 3985-4001:
17. (b) S. Hanessian, E. Therrien, K. Granberg and I. Nilsson, Bioorg. Med. Chem. Lett., 2002, 12, 2907-2911;
18. (c) N. H. Hauel, H. Nar, H. Priepke, U. Ries, J.-M. Stassen and W. Wienen, J. Med. Chem., 2002, 45, 1757-1766;
19. (d) for a review, see: J. B. M. Rewinkel and A. E. P. Adang, Curr. Pharm. Des., 1999, 5, 1043-1075.
20. R. Talhout and J. B. F. N. Engberts, Eur. J. Biochem., 2001, 268, 1554-1560.
21. (a) M. Recanatini, T. Klein, C.-Z. Yang, J. McClarin, R. Langridge and C. Hansch, Mol. Pharmacol., 1986, 29, 436-446;
22. (b) D. Labes and V. Hagen, Pharmazie, 1979, 34, 649-653:
23. (c) M. Mares-Guia, D. L. Nelson and E. Rogana, J. Am. Chem. Soc., 1977, 99, 2331-2336;
24. (d) B. A. Katz, R. Mackman, C. Luong, K. Radika, A. Martelli, P. A. Sprengeler, J. Wang, H. Chan and L. Wong, Chem. Biol., 2000, 7, 299-312.
25. (a) P. E. J. Sanderson, M. G. Stanton, B. D. Dorsey, T. A. Lyle, C. McDonough, W. M. Sanders, K. L. Savage, A. M. Naylor-Olsen, J. A. Krueger, S. D. Lewis, B. J. Lucas, J. J. Lynch and Y. Yan, Bioorg. Med. Chem. Lett., 2003, 13, 795-798;
26. (b) T. J. Tucker, S. F. Brady, W. C. Lumma, S. D. Lewis, S. J. Gardell, A. M. Naylor-Olsen, Y. Yan, J. T. Sisko, K. J. Stauffer, B. J. Lucas, J. J. Lynch, J. J. Cook, M. T. Stranieri, M. A. Holahan, E. A. Lyle, E. P. Baskin, I.-W. Chen, K. B. Dancheck, J. A. Krueger, C. M. Cooper and J. P. Vacca, J. Med. Chem., 1998, 41, 3210-3219;
27. (c) Y. St-Denis, S. Lévesque, B. Bachand, J. J. Edmunds, L. Leblond, P. Préville, M. Tarazi, P. D. Winocour and M. A. Siddiqui, Bioorg. Med. Chem. Lett., 2002, 12, 1181-1184.
28. (a) B. A. Katz, P. A. Sprengeler, C. Luong, E. Verner, K. Elrod, M. Kirtley, J. Janc, J. R. Spencer, J. G. Breitenbucher, H. Hui, D. McGee, D. Allen, A. Martelli and R. L. Mackman, Chem. Biol., 2001, 8, 1107-1121;
29. (b) K. Lee, C. W. Park, W.-H Jung, H. D. Park, S. H. Lee, K. H. Chung, S. K. Park, O. H. Kwon, M. Kang, D.-H. Park, S. K. Lee, E. E. Kim, S. K. Yoon and A. Kim, J. Med. Chem., 2003, 46, 3612-3622.
30. J. W. Essex, D. L. Severance, J. Tirado-Rives and W. L. Jorgensen, J. Phys. Chem. B., 1997, 101, 9663-9669.
31. (a) C. R. W. Guimaraes and R. B. de Alencastro, J. Phys. Chem. B., 2002, 106, 466-476;
32. (b) S. M. Schwarzl, T. M. Tschopp, J. C. Smith and S. Fischer, J. Comput. Chem., 2002, 23, 1143-1149;
33. (c) C. F. Wong and J. A. McCammon, J. Am. Chem. Soc., 1986, 108, 3830-3832;
34. (d) G. Náray-Szabó, J. Am. Chem. Soc., 1984, 106, 4584-4589;
35. (e) H.-J. Henkel, D. Labes and V. Hagen, Pharmazie, 1983, 38, 342-346.
36. C. J. Dinsmore, M. J. Bogusky, J. C. Culberson, J. M. Bergman, C. F. Homnick, C. B. Zartman, S. D. Mosser, M. D. Schaber, R. G. Robinson, K. S. Koblan, H. E. Huber, S. L. Graham, G. D. Hartman, J. R. Huff and T. M. Williams, J. Am. Chem. Soc., 2001, 123, 2107-2108.
37. I. M. Bell, S. N. Gallicchio, M. Abrams, L. S. Beese, D. C. Beshore, H. Bhimnathwala, M. J. Bogusky, C. A. Buser, J. C. Culberson, J. Davide, M. Ellis-Hutchings, C. Fernandes, J. B. Gibbs, S. L. Graham, K. A. Hamilton, G. D. Hartman, D. C. Heimbrook, C. F. Homnick, H. E. Huber, J. R. Huff, K. Kassahun, K. S. Koblan, N. E. Kohl, R. B. Lobell, J. J. Lynch Jr., R. Robinson, A. D. Rodrigues, J. S. Taylor, E. S. Walsh, T. M. Williams and C. B. Zartman, J. Med. Chem., 2002, 45, 2388-2409.
38. (a) R. Grigg, J. Idle, P. McMeekin and D. Vipond, J. Chem. Soc., Chem. Commun., 1987, 49-51;
39. (b) O. Tsuge and S. Kanemasa, Adv. Heterocycl. Chem., 1989, 45, 231-349.
40. C.-B. Xue, J. Wityak, T. M. Sielecki, D. J. Pinto, D. G. Batt, G. A. Cain, M. Sworin, A. L. Rockwell, J. F. Roderick, S. Wang, M. J. Orwat, W. E. Frietze, L. L. Bostrom, J. Liu, C. A. Higley, F. W. Rankin, A. E. Tobin, G. Emmett, G. K. Lalka, J. Y. Sze, S. V. Di Meo, S. A. Mousa, M. J. Thoolen, A. L. Racanelli, E. A. Hausner, T. M. Reilly, W. F. DeGrado, R. R. Wexler and R. E. Olson, J. Med. Chem., 1997, 40, 2064-2084.
41. A. J. Bridges, A. Lee, E. C. Maduakor and C. E. Schwartz, Tetrahedron Lett., 1992, 33, 7499-7502.
42. K. J. Rutan, F. J. Heldrich and L. F. Borges, J. Org. Chem., 1995, 60, 2948-2950.
43. B. D. Judkins, D. G. Allen, T. A. Cook, B. Evans and T. E. Sardharwala, Synth. Commun., 1996, 26, 4351-4367.
44. E. A. Meyer, R. K. Castellano and F. Diederich, Angew. Chem., Int. Ed., 2003, 42, 1210-1250.
45. (a) J. D. Dunitz and R. Taylor, Chem. Eur. J., 1997, 3, 89-98;
46. (b) J. A. K. Howard, V. J. Hoy, D. O'Hagan and G. T. Smith, Tetrahedron, 1996, 52, 12613-12622.
47. T. Steiner, Angew. Chem., Int. Ed., 2002, 41, 48-76.
48. (a) J. P. Snyder, N. S. Chandrakumar, H. Sato and D. C. Lankin, J. Am. Chem. Soc., 2000, 122, 544-545;
49. (b) T. J. Barbarich, C. D. Rithner, S. M. Miller, O. P. Anderson and S. H. Strauss, J. Am. Chem. Soc., 1999, 121, 4280-4281.
50. (a) G. R. Desiraju, Acc. Chem. Res., 2002, 35, 565-573;
51. (b) V. R. Thalladi, H.-C. Weiss, D. Bläser, R. Boese, A. Nangia and G. R. Desiraju, J. Am. Chem. Soc., 1998, 120, 8702-8710.
52. A. J. Mountford, D. L. Hughes and S. J. Lancaster, Chem. Commun., 2003, 2148-2149.
53. (a) J. Parsch and J. W. Engels, J. Am. Chem. Soc., 2002, 124, 5664-5672;
54. (b) G. M. Dubowchik, V. M. Vrudhula, B. Dasgupta, J. Ditta, T. Chen, S. Sheriff, K. Sipman, M. Witmer, J. Tredup, D. M. Vyas, T. A. Verdoorn, S. Bollini and A. Vinitsky, Org. Lett., 2001, 3, 3987-3990;
55. (c) A. DerHovanessian, J. B. Doyon, A. Jain, P. R. Rablen and A.-M. Sapse, Org. Lett., 1999, 1, 1359-1362.
56. (a) E. J. Corey and T. W. Lee, Chem. Commun., 2001, 1321-1329;
57. (b) V. V. Grushin and W. J. Marshall, Angew. Chem., Int. Ed., 2002, 41, 4476-4479.
58. P. W. Baures, A. M. Beatty, M. Dhanasekaran, B. A. Helfrich, W. Pérez-Segarra and J. Desper, J. Am. Chem. Soc., 2002, 124, 11315-11323.
59. K. Nishide, Y. Hagimoto, H. Hasegawa, M. Shiro and M. Node, Chem. Commun., 2001, 2394-2395.
60. 1 F...CN < 4.0 Å.
61. W. R. Croasmun and R. M. K. Carlson (eds), Two-Dimensional NMR Spectroscopy, 2nd ed., VCH, Weinheim, 1994.
62. MedChem02 database, Daylight Chemical Information Systems, Inc., 27401, Los Altos #360, Mission Viejo, CA 92691, USA.
63. J. Clark and D. D. Perrin, Q. Rev. Chem. Soc., 1964, 18, 295-320.
64. Spartan '04 Windows, Copyright 2003, Wavefunction, Inc., 18401 Von Karman Ave., Irvine, CA 92612.
65. Unfavorable C-F dipole-lone pair interactions were elegantly taken in consideration to explain the primary stereoelectronic effect in the Baeyer-Villiger reaction; see: C. M. Crudden, A. C. Chen and L. A. Calhoun, Angew. Chem., Int. Ed., 2000, 39, 2852-2855.
66. B. A. Katz, R. Mackman, C. Luong, K. Radika, A. Martelli, P. A. Sprengeler, J. Wang, H. Chan and L. Wong, Chem. Biol., 2000, 7, 299-312.
67. K. Hilpert, J. Ackermann, D. W. Banner, A. Gast, K., Gubernator, P. Hadváry, L. Labler, K. Müller, G. Schmid, T. B. Tschopp and H. van de Waterbeemd, J. Med. Chem., 1994, 37, 3889-3901.
68. (a) L. Sebo, B. Schweizer and F. Diederich, Helv. Chim. Acta, 2000, 83, 80-92;
69. (b) T. Grawe, G. Schäfer and T. Schrader, Org. Lett., 2003, 5, 1641-1644.
70. (a) P. R. Gerber and K. Müller, J. Comput.-Aided Des., 1995, 9, 251-268;
71. (b) Gerber Molecular Design (http://www.moloc.ch).
72. (a) A. Albert and E. P. Serjeant, The Determination of Ionization Constants, T&A Constable Ltd., Edinburgh, 1971:
73. a and log P Determination, Revision, 1.0, August 1993;
74. a instruction manual, January 1999.
75. A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. Burla, G. Polidori and M. Camalli, J. Appl. Crystallogr., 1994, 27, 435.
76. G. M. Sheldrick, SHELX-97 program for the refinement of crystal structures, University of Göttingen, Germany, 1997.