Investigation of mechanism-based thrombin inhibitors: Implications of a highly conserved water molecule for the binding of coumarins within the S pocket

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 7, 2006, Pages 2017-2021

  Frédérick, Raphaël ^a   Charlier, Caroline ^a   Robert, Séverine ^a   Wouters, Johan ^a   Masereel, Bernard ^a   Pochet, Lionel ^a  

^a UNIVERSITY OF NAMUR   (Belgium)

Author keywords

Coumarins; Docking; Mechanism based inhibitor; Serine protease; Thrombin

Indexed keywords

AMINE; ANILINE; COUMARIN DERIVATIVE; GUANIDINE; GUANIDINE DERIVATIVE; THROMBIN INHIBITOR; WATER;

ARTICLE; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

ANTITHROMBINS; BINDING SITES; COUMARINS; MODELS, MOLECULAR; WATER;

EID: 33144488450     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.12.070     Document Type: Article

References (18)

1. K.G. Mann Thromb. Haemost. 82 1999 165
2. B. Dahlback Lancet 355 2000 1627
3. R. Frederick, S. Robert, C. Charlier, J. de Ruyck, J. Wouters, B. Pirotte, B. Masereel, and L. Pochet J. Med. Chem. 48 2005 7592
4. M.S. Bernatowicz, Y. Wu, and G.R. Matsueda Tetrahedron Lett. 34 1993 3389
5. K.S. Kim, and L. Qian Tetrahedron Lett. 34 1993 7677
6. K. Feichtinger, H. Sings, T. Baker, K. Matthews, and M. Goodman J. Org. Chem. 63 1998 8432
7. K. Feichtinger, C. Zapf, H. Sings, and M. Goodman J. Org. Chem. 63 1998 3804
8. 3, 400 MHz) δ 1.50 (s, 18H), 3.24 (m, 2H), 4.40 (t, 2H), 8.50 (s, 1H), 11.27 (s, 1H).
9. L. Pochet, C. Doucet, M. Schynts, N. Thierry, N. Boggetto, B. Pirotte, K.Y. Jiang, B. Masereel, P. de Tullio, J. Delarge, and M. Reboud-Ravaux J. Med. Chem. 39 1996 2579
10. C. Doucet, L. Pochet, N. Thierry, B. Pirotte, J. Delarge, and M. Reboud-Ravaux J. Med. Chem. 42 1999 4161
11. 3 with an incubation time of 10 min for the enzyme/inhibitor reaction.
12. For experimental details, see Ref. 3.
13. J.P. Vacca Curr. Opin. Chem. Biol. 4 2000 394
14. G. Jones, P. Willett, R.C. Glen, A.R. Leach, and R. Taylor J. Mol. Biol. 267 1997 727
15. Discover 3, version 2.98; Accelrys Inc.: San Diego, CA, 1998.
16. Insight II, version 2000; Accelrys Inc.: San Diego, CA, 2000.
17. M.L. Verdonk, G. Chessari, J.C. Cole, M.J. Hartshorn, C.W. Murray, J.W. Nissink, R.D. Taylor, and R. Taylor J. Med. Chem. 48 2005 6504
18. L. Pochet, M. Dieu, R. Frédérick, A.M. Murray, I. Kempen, B. Pirotte, and B. Masereel Tetrahedron 59 2003 4557