Nonpeptide glycoprotein IIb/IIIa inhibitors. 13. Design and synthesis of an orally active pyrazolopiperazinone nonpeptide fibrinogen receptor antagonist

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 12, 1997, Pages 1531-1536

  Askew, B C ^a   McIntyre, C J ^a   Hunt, C A ^a   Claremon, D A ^a   Baldwin, J J ^a,b   Anderson, P S ^a,c   Gould, R J ^a   Lynch, R J ^a   Chang, C C T ^a   Cook, J J ^a   Lynch, J J ^a   Holahan, M A ^a   Sitko, G R ^a   Stranieri, M T ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b PHARMACOPEIA INC   (United States)

^c DUPONT COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE DIPHOSPHATE; COLLAGEN; FIBRINOGEN RECEPTOR ANTAGONIST; L 734115; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL ADHESION; CONTROLLED STUDY; DOG; DOSE RESPONSE; DRUG DESIGN; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; NONHUMAN; ORAL DRUG ADMINISTRATION; RHESUS MONKEY; THROMBOCYTE AGGREGATION;

EID: 0031001454     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00256-4     Document Type: Article

References (19)

1. (a) Falk, E. Circulation 1985, 71, 699.
2. (b) Coller, B. S. New Eng. J. Med. 1990, 322, 33 (in Seminars in Medicine of the Beth Israel Hospital, Boston).
3. (c) Cadroy, Y.; Harker, L. A. In Cardiovascular Pharmacology, 3rd ed.; M. Antonaccio, Ed.; Raven: New York, 1990; pp 515-539.
4. (d) Scharf, R. E.; Harker, L. A. Blut 1987, 509, 118.
5. (a) Phillips, D. R. ; Fitzgerald, L. A.; Charo, I. F.; Parise, L. V. Blood 1988, 71, 831.
6. (b) Peerschke, E. I.; Zucker, M. B.; Grant, R. A.; Egan, J. J.; Johnson, M. M. Blood 1980, 55, 841.
7. For recent reviews see: (a) Jakabowski, J. A.; Smith, G. F.; Sall, D. J. Ann. Rept. Med. Chem. 1992, 27, 99.
8. (b) Weller, T.; Alig, L.; Muller, M. H.; Kouns, W. C.; Steiner, B., Drugs Fut. 1994, 19, 461.
9. (c) Cook, N. S.; Kottirsch, G.; Zerwes, H-G. Drugs Fut. 1994, 19, 135.
10. Askew, B. C.; McIntyre, C. J.; Hunt, C. A.; Claremon, D. A.; Gould, R. J.; Lynch, R. J. Armstrong, D. J. Bioorg. Med. Chem. Lett. 1995, 5, 475.
11. 1H NMR, HPLC, MS, CHN) were consistent with the assigned structures.
12. (a) Duggan, M. E.; Naylor-Olsen, A. M.; Perkins, J. J.; Anderson, P. S.; Chang, C. C.-C-T.; Cook, J. J.; Gould, R. G.; Ihle, N. C.; Hartman, G. D.; Lynch J. J.; Lynch, R. J.; Manno, P. D.; Schaffer, L. W.; Smith, R. L. J. Med. Chem. 1995 38, 3332.
13. (b) Zablocki, J. A.; Rico, J. G. Garland, R. B.; Rogers, T. E.; Williams, K.; Schretzman, L. A.; Rao. S. A.; Bovy, P. R.; Tjoeng, F. S.; LindMarck, R. J.; Toth, M. V.; Zupec, M. E.; McMackins, D. E.; Adams, S. P.; Miyano, M. ; Markos, C. S.; Milton, M. N.; Paulson, S.; Herin, M.; Jacqmin, P.; Nicholson, N. S.; Pranzer-Knodle, S. G.; Haas, N. F.; Page, J. D.; Szalony, J. A.; Taite, B. B.; Salyers, A. K.; King, L.; Campion, J.; Feign, L. P. J. Med. Chem. 1995 38, 2379.
14. 2O: C, 50.13; H, 6.91; N, 16.17 ; found: C, 50.17; H, 6.81; N, 16.38.
15. (a) Egbertson, M. S.; Naylor, A. M.; Hartman, G. D.; Cook, J. J.; Gould, R. J.; Holahan, M. A.; Lynch, J. J.; Lynch, R. J.; Stranieri, M. T.; Vassallo, L. M. Bioorg. Med. Chem. Lett. 1994, 4, 1835.
16. (b) Naylor, A. M.; Egbertson, M. S.; Vassallo, L. M.; Birchenough, L. A.; Zhang, G. X.; Gould, R.J .; Hartman, G. D. Bioorg. Med. Chem. Lett. 1994, 4, 1841.
17. (c) Egbertson, M. S.; Hartman, G. D.; Gould, R. J.; Bednar, B; Bednar, R. A.; Cook, J. J.; Gaul, L. S.; Holahan, M. A.; Libby, L. A.; Lynch, J. J.; Lynch, R. J.; Sitko, G. R.; Stranieri, M. T.; Vassallo, L.M. Bioorg. Med. Chem. Lett. in press.
18. 50 values of 24, 26, and 28 nM for the inhibition of ADP mediated platelet aggregation of human, dog, and rhesus PRP, respectively.
19. Albeida, S. M.; Daise, M.; Levine, E. M; Buck, C. A. J. Clin. Invest. 1989, 83, 1992.