Nonpeptide glycoprotein IIb/IIIa inhibitors: Substituted quinazolinediones and quinazolinones as potent fibrinogen receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 5, 1998, Pages 483-486

  Liverton, Nigel J ^a   Armstrong, Donna J ^a   Claremon, David A ^a   Remy, David C ^a   Baldwin, John J ^a   Lynch, Robert J ^a   Zhang, Guixiang ^a   Gould, Robert J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTITHROMBOCYTIC AGENT; FIBRINOGEN RECEPTOR; FIBRINOGEN RECEPTOR ANTAGONIST; GLYCOPROTEIN; L 732821; QUINAZOLINEDIONE DERIVATIVE; QUINAZOLINONE DERIVATIVE; TIROFIBAN; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; THROMBOCYTE; THROMBOSIS PREVENTION;

HUMANS; PLATELET AGGREGATION INHIBITORS; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; QUINAZOLINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032478055     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00047-X     Document Type: Article

References (18)

1. 1. Knoebel, S. B. J. Am Coll. Card. 1989, 14, 813.
2. 2. Resnekov, L.; Chediak, J.; Hirsh, J.; Lewis, H. D. Chest 1988, 95(suppl), 525.
3. 3. Coller, B. S. N. Eng. J. Med 1990, 322, 33.
4. 4. Cook, N. S.; Kottirsch, G.; Zerwes, H.-G. Drugs of the Future 1994, 19, 135.
5. 5. Gan, Z.-R.; Gould, R. J.; Jacobs, J. W.; Friedman, P. A.; Polokoff, M. A. J. Biol. Chem. 1988, 263, 19827.
6. 6. Nutt, R. F.; Brady, S. F.; Sisko, J. T.; Ciccarone, T. M.; Colton, C. D.; Levy, M. R.; Gould, R. J.; Zhang, G.; Friedman P. A.; Veber, D. A. Proc. Eur. Pept. Symp. 21st 1990, 784.
7. 7. Hartman, G. D.; Egbertson, M. S.; Halczenko, W.; Laswell, W. L.; Duggan, M. E.; Smith, R. L.; Naylor, A. M.; Manno, P. D.; Lynch, R. J.; Zhang, G.; Chang C. T.-C.; Gould, R. J. J. Med. Chem. 1992, 35, 4640.
8. 8. Egbertson, M. S.; Hartman, G. D.; Gould, R. J.; Bednar, B.; Bednar, R. A.; Cooks, J. J.; Gaul, S. L.; Holahan, M. A.; Libby, L. A.; and Lynch, J. J., Jr. Bioorg. Med. Chem. Lett. 1996, 6, 2519.
9. 9. For example ketanserin: Michiels, M.; Monbaliu, J.; Meuldermans, W.; Hendriks, R.; Geerts; R. Woestenborghs; R. Heykants, J. Arzneim.-Forsch. 1988, 38, 775 and methaqualone.
10. 10. The compounds described in this paper were prepared as racemic mixtures.
11. 11. BOC aminoethylpiperidine was prepared analogously to BOC 4-aminomethylpiperidine: Prugh, J. D.; Birchenough, L. A.; Egbertson, M. S. Synth. Commun. 1992, 22, 2357.
12. 12. Baillargeon, V. P.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 452.
13. 13. Dalcanale, E.; Montanari, F. J. Org. Chem. 1986, 51, 567.
14. 14. Prepared analogously to the α-CBZ derivative: Egbertson, M. S.; Homnick, C. F.; Hartman, G. D. Synth. Commun. 1993, 23, 703.
15. 15. Final compounds were generally purified by reverse phase HPLC on a C18 column and lyophilized to give the trifluoroacetate salt.
16. 16. Fournet, G.; Balme, G.; Gore, J. Tetrahedron Lett. 1989, 30, 69.
17. 17. Prepared from propargylglycine by reaction with HCl/EtOH followed by 1-butanesulfonyl chloride/ diisopropylethy lamine.
18. 18. McDowell, R. S.; Blackburn, B. K.; Gadek, T. R.; McGee, L. R.; Rawson, T.; Reynolds, M. E.; Robarge, K. D.; Somers, T. C.; Thorsett, E. D.; Tischler, M.; Webb II, R. R.; Venuti, M. C. J. Am. Chem. Soc. 1994, 116, 5077.