Synthesis, evaluation, and crystallographic analysis of L-371,912: A potent and selective active-site thrombin inhibitor

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 1, 1997, Pages 67-72

  Lyle, Terry A ^a   Chen, Zhongguo ^a   Appleby, Sandra D ^a   Freidinger, Roger M ^a   Gardell, Stephen J ^a   Lewis, S Dale ^a   Li, Ying ^a   Lyle, Elizabeth A ^a   Lynch Jr , Joseph J ^a   Mulichak, Anne M ^a   Ng, Assunta S ^a   Naylor Olsen, Adel M ^a   Sanders, William M ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

L 370518; L 371912; SERINE PROTEINASE; THROMBIN; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL MODEL; ARTERY THROMBOSIS; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG SYNTHESIS; ENZYME BINDING; HUMAN; NONHUMAN; RAT; X RAY DIFFRACTION;

EID: 0031024174     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00583-5     Document Type: Article

References (15)

1. (a) Tapparelli, C.; Metternich, R.; Ehrhardt, C.; Cook, N. S. Trends Pharmacol. Sci. 1993,14, 366.
2. (b) Lyle, T. A. Perspect. Drug Discovery Des. 1993, 1, 453 and references sited therein.
3. (c) Bode, W.; Mayer, I.; Baumann, U.; Huber, R.; Stone, R. S.; Hofsteenge, J. EMBO J. 1989, 8, 3417.
4. Brady, S. F.; Lewis, S. D.; Colton, C. D.; Stauffer, K. J.; Sisko, J. T.; Ng, A. S.; Homnick, C. F.; Bogusky, M. J.; Shafer, J. A.; Veber, D. F.; Nutt, R. F. Proc. 14th Amer. Peptide Symp. 1995, 0.
5. (a) Brady, S. F.; Sisko, J. T.; Stauffer, K. J.; Colton, C. D.; Qiu, H.; Lewis, S. D.; Ng, A. S.; Shafer, J. A.; Bogusky, M. J.; Veber, D. F.; Nutt, R. F. Bioorg. Med. Chem. 1995, 3, 1063.
6. (b) Lewis, S. D.; Ng, A. S.; Lyle, E. A.; Mellott, M. J.; Appleby, S. D.; Brady, S. F.; Stauffer, K. J.; Sisko, J. T.; Mao, S-S.; Veber, D. F.; Nutt, R. F.; Lynch, J. J.; Cook, J. J.; Gardell, S. J.; Shafer, J. A. Thromb. Haemostasis 1995, 3, 1063.
7. Cutrona, K. J.; Sanderson, P. E. J.; Tetrahedron Lett. 1996, 37, 5045.
8. i determinations were carried out as described in refs 3a,b and in: Lewis, S. D.; Ng, A. S.; Baldwin, J. J.; Fusetani, N.; Naylor, A. M.; Shafer, J. A. Thromb. Res. 1993, 70, 173.
9. Kurz, K. D.; Main, B. W.; Sandusky, G. E. Thromb. Res. 1990, 60, 269.
10. Lyle, E. A.; Lynch, Jr. J. J.; Cook, J. J.; Unpublished results.
11. Merck Research Laboratories Unpublished results.
12. Chen, Z.; Li, Y.; Mulichak, A. M.; Lewis, S. D.; Shafer, J. A. Arch. Biochem. Biophys. 1995, 322, 198.
13. Brunger, A. T.; Kuriyan, K.; Karplus, M. Science 1987, 235, 458.
14. Sack, J. S. J. Mol. Graphics 1988, 6, 224.
15. Coordinates have been deposited in the Brookhaven Protein Data Bank.