Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 23, 2010, Pages 6925-6928

  Hanessian, Stephen ^a   Larsson, Andreas ^a,c   Fex, Tomas ^b   Knecht, Wolfgang ^b   Blomberg, Niklas ^b  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

^b ASTRAZENECA R AND D   (Sweden)

^c UMEÅ UNIVERSITY   (Sweden)

Author keywords

Enzyme inhibitor; Macrocycle; Thrombin

Indexed keywords

BLOOD CLOTTING FACTOR 11A; INDOLE DERIVATIVE; MACROCYCLIC COMPOUND; SERINE PROTEINASE; THROMBIN;

ARTICLE; CYCLIZATION; DRUG ACTIVITY; DRUG DESIGN; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; IC 50; MOLECULAR MODEL;

ANTICOAGULANTS; BLOOD COAGULATION; DRUG DESIGN; FACTOR XIA; INDOLES; SERINE PROTEINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 78149280530     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.09.141     Document Type: Article

References (47)

1. V.F. Tapson N. Engl. J. Med. 358 2008 1037
2. S. Haas Thromb. Res. 109 2003 S31
3. S. Haas J. Thromb. Thrombolysis 25 2008 52
4. J. Hirsh, R. Raschke, T.E. Warkentin, J.E. Dalen, D. Deykin, and L. Poller Chest 108 1995 258S
5. J. Harenberg, and M. Wehling Semin. Thromb. Hemost. 34 2008 39
6. J. Hirsh, M. O'Donnell, and J.I. Weitz Blood 105 2005 453
7. R. Rai, P.A. Sprengeler, K.C. Elrod, and W.B. Young Curr. Med. Chem. 8 2001 101
8. T. Steinmetzer, and J. Sturzebecher Curr. Med. Chem. 11 2004 2297
9. R.M. Scarborough, A. Pandey, and X. Zhang Annu. Rep. Med. Chem. 40 2005 85
10. S. Srivastava, L.N. Goswami, and D.K. Dikshit Med. Res. Rev. 25 2005 66
11. L. Jin, P. Pandey, R.E. Babine, J.C. Gorga, K.J. Seidl, E. Gelfand, D.T. Weaver, S.S. Abdel-Meguid, and J.E. Strickler J. Biol. Chem. 6 2005 4704
12. P.N. Walsh Thromb. Haemost. 86 2001 75
13. R. Asakai, D.W. Chung, E.W. Davie, and U. Seligsohn N. Engl. J. Med. 325 1991 153
14. D. Gailani, and T. Renné Arterioscler. Thromb. Vasc. Biol. 27 2007 2507
15. D. Gailani, and T. Renné J. Thromb. Haemost. 5 2007 1106
16. N. Mackman Nature 451 2008 914
17. J.D.A. Tyndall, and D.P. Fairlie Curr. Med. Chem. 8 2001 893
18. E.M. Driggers, S.P. Hale, J. Lee, and N.K. Terrett Nat. Rev. Drug Discovery 7 2008 608
19. Y. Hamada, and T. Shioiri Chem. Rev. 105 2005 4441
20. S. Hanessian, J.R. Del Valle, Y. Xue, and N. Blomberg J. Am. Chem. Soc. 128 2006 10491
21. K. Ersmark, J.R. Del Valle, and S. Hanessian Angew. Chem., Int. Ed. 47 2008 1202
22. M. Murakami, S. Kodani, K. Ishida, H. Matsuda, and K. Yamaguchi Tetrahedron Lett 38 1997 3035
23. N. Fusetani, and S. Matsunaga J. Am. Chem. Soc. 112 1990 7053
24. Y. Nakao, S. Matsunaga, and N. Fusetani Bioorg. Med. Chem. 3 1995 1115
25. B.E. Maryanoff, H.-C. Zhang, M.N. Greco, K.A. Glover, J.A. Kauffman, and P. Andrade-Gordon Bioorg. Med. Chem. 3 1995 1025
26. M.N. Greco, E.T. Powell, L.R. Hecker, P. Andrade-Gordon, J.A. Kauffman, J.M. Lewis, V. Ganeshfi, A. Tulinsky, and B.E. Maryanoff Bioorg. Med. Chem. Lett. 6 1996 2947
27. P.G. Nantermet, and H.G. Selnick Tetrahedron Lett. 44 2003 2401
28. P.G. Nantermet, J.C. Barrow, C.L. Newton, J.M. Pellicore, M. Young, S.D. Lewis, B.J. Lucas, J.A. Krueger, D.R. McMasters, Y. Yan, L.C. Kuo, J.P. Vacca, and H.G. Selnick Bioorg. Med. Chem. Lett. 13 2003 2781
29. H. Deng Bioorg. Med. Chem. Lett. 16 2006 3049
30. T.I. Lazarova, L. Jin, M. Rynkiewicz, J.C. Gorga, F. Bibbins, H.V. Meyers, R. Babineb, and J. Strickler Bioorg. Med. Chem. Lett. 16 2006 5022
31. J. Lin J. Med. Chem. 49 2006 7781
32. W.A. Schumacher, S.E. Seiler, T.E. Steinbacher, A.B. Stewart, J.S. Bostwick, K.S. Hartl, E.C. Liu, and M.L. Ogletree Eur. J. Pharmacol. 570 2007 167
33. M.S. Buchanan, A.R. Carroll, D. Wessling, M. Jobling, V.M. Avery, R.A. Davis, Y. Feng, Y. Xue, L. Öster, T. Fex, J. Deinum, J.N.A. Hooper, and R.J. Quinn J. Med. Chem. 51 2008 3583
34. L. Jin, P. Pandey, R.E. Babine, D.T. Weaver, S.S. Abdel-Meguid, J.E. Strickler, Acta. Crystallogr, and D. Sect Acta Crystallogr., Sect. D 2005 1418 61
35. Abdel-Meguid, S. S.; Babine, R. E.; Deng, H.; Jin, L.; Lin, J.; Magee, S. R.; Meyers, H. V.; Pandey, P.; Rynkiewicz, M. J.; Weaver, D. T. PCT Int. Appl., 2004; 925. CODEN: PIXXD2 WO 2004103270.
36. A conformational ensemble generated in MOE (Molecular Operating Environment, CCG, Montréal, Canada) using a stochastic conformational search (default settings) was docked in the active site of Factor XIa (PDB code: 1ZSL ) using the rigid docking program FRED (OpenEye Scientific Software, New Mexico, USA).
37. G. Simon, H. Couthon-Gourves, J.-P. Haelters, B. Corbel, N. Kervarec, F. Michaud, and L. Meijer J. Heterocycl. Chem. 44 2007 793
38. M. Abarbri, J. Thibonnet, L. Bérillon, F. Dehmel, M. Rottländer, and P. Knochel J. Org. Chem. 65 2000 4618
39. S. Hanessian, S. Giroux, and A. Larsson Org. Lett. 8 2006 5481
40. A.S. Thompson, G.R. Humphrey, A.M. DeMarco, D.J. Mathre, and E.J.J. Grabowski J. Org. Chem. 58 1993 5886
41. B.F. Bonini, G. Kemperman, S.T.H. Willems, M. Fochi, G. Mazzanti, and B. Zwanenburg Synlett 1998 1411
42. H. Li, X. Jiang, Y. Ye, C. Fan, T. Romoff, and M. Goodman Org. Lett. 1 1999 91
43. O.R. Suárez-Castillo, L.A. Montiel-Ortega, M. Meléndez- Rodríguez, and M. Sánchez-Zavala Tetrahedron Lett. 48 2007 17
44. T.K. Chakraborty, and A. Ghosh Synlett 2002 2039
45. C.K.Z. Andrade, R.O. Rocha, O.E. Vercillo, W.A. Silva, and R.A.F. Matos Synlett 2003 2351
46. Compound (E)-34 could not be tested due to insolubility in the conditions required. No inhibition of FIXa could be detected at 300 μM.
47. A conformational ensemble generated in MOE (Molecular Operating Environment, CCG, Montréal, Canada) using a stochastic conformational search (default settings except 60 kJ energy cutoff, 0.9 RMS tolerance, and amide bond rotation allowed), was docked in the active site of thrombin (PDB code: 1NT1 ) using the rigid docking program FRED (OpenEye Scientific Software, New Mexico, USA).