Nonpeptide GPIIB/IIIA inhibitors. 10. Centrally constrained alpha-sulfonamides are potent inhibitors of platelet aggregation

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 21, 1996, Pages 2519-2524

  Egbertson, M S ^a   Hartman, G D ^a   Gould, R J ^a   Bednar, B ^a   Bednar, R A ^a   Cook, J J ^a   Gaul, S L ^a   Holahan, M A ^a   Libby, L A ^a   Lynch Jr , J J ^a   Lynch, R J ^a   Sitko, G R ^a   Stranieri, M T ^a   Vassallo, L M ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTITHROMBOCYTIC AGENT; FIBRINOGEN RECEPTOR; FIBRINOGEN RECEPTOR ANTAGONIST; L 692884; L 709780; L 736622; SULFONAMIDE; TIROFIBAN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DOG; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; INTRAVENOUS DRUG ADMINISTRATION; NONHUMAN; ORAL DRUG ADMINISTRATION; STRUCTURE ACTIVITY RELATION; THROMBOCYTE AGGREGATION;

ANIMALIA; CANIS FAMILIARIS;

EID: 16044367054     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00473-8     Document Type: Article

References (15)

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2. 1. Philips, D. R.; Charo, I. F.; Parise; L. V. Blood 1988, 71, 831; (b) Philips, D. R.; Kieffer, N. Annu. Rev. Cell Biol. 1990, 6, 329.
3. 2. Cook, N. S.; Kottirsch, G.; Zerwes, H. -G.; Drugs Fut. 1994, 19, 135.
4. 3. 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.
5. 4. Egbertson, M. S.; Chang, C. T. C.; Duggan, M. E.; Gould, R. J.; Halczenko, W.; Hartman, G. D.; Laswell, W. L.; Lynch, J. J. Jr.; Lynch R. J.; Manno, P. M.; Naylor, A. M.; Prugh, J. D.; Ramjit, D. R.; Sitko, G. R.; Smith, R. S.; Turchi, L. M.; Zhang, G. J. Med. Chem. 1994, 37, 2537.
6. 5. Egbertson, M. S.; Naylor, A. M.; Hartman, G. D.; Cook, J. J.; Gould, R. J.; Holahan, M. A.; Lynch, J. J. Jr.; Lynch, R. J.; Stranieri, M. T.; Vassallo, L. M. Bioorg. Med. Chem. Lett. 1994, 4, 1835.
7. 6. Egbertson, M. S.; Bednar, B.; Bednar, R. A.; Hartman, G. D.; Gould, R. J.; Lynch, R. J.; Vassallo, L. M.; Young, S. D. Bioorg. Med. Chem. Lett. 1996, 6, 1415.
8. 7. Egbertson, M. S.; Homnick, C. F.; Hartman, G .D. Synth.Commun. 1993, 23, 703.
9. 8. All compounds were characterized by NMR, TLC, HPLC, High Resolution Mass Spectroscopy and H, C, N analysis.
10. 50 determinations was ± 20%.
11. 10. Lynch, J. J. Jr.; Cook, J. J.; Sitko, G. R.; Holahan, M. A.; Ramjit, D. R.; Mellott, M. J.; Strainieri, M. T.; Stabilito, I. I.; Zhang, G.; Lynch, R. J.; Manno, P. D.; Chang, C. T.-C.; Egbertson, M. S.; Halczenko, W.; Duggan, M. E.; Laswell, W. L.; Vassallo, L. M.; Shafer, J. A.; Anderson, P. S.; Friedman, P. A.; Hartman, G. D.; and Gould, R. J. J. Pharm. Exp. Ther. 1995, 272, 20.
12. 8 platelets/mL, 20,000 to 100,000 receptors per platelet).
13. 50 determinations was ± 20%.
14. 13. Bohumil Bednar, Rodney A. Bednar, unpublished results. The two assays described here will be discussed in greater detail in subsequent publications.
15. D values in the low nanomolar, but not the sub-nanomolar range.