Synthesis and evaluation of pyrazolo[3,4-b]quinoline ribofuranosides and their derivatives as inhibitors of oncogenic Ras

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 2, 1996, Pages 195-200

  Wolin, Ronald ^a   Wang, David ^a   Kelly, Joseph ^a   Afonso, Adriano ^a   James, Linda ^a   Kirschmeier, Paul ^a   McPhail, Andrew T ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b DUKE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GUANOSINE TRIPHOSPHATE; NUCLEOSIDE DERIVATIVE; PROTEIN P21; PYRAZOLO[3,4 B] QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; DRUG SYNTHESIS; ENZYME ACTIVATION; ONCOGENE RAS; SIGNAL TRANSDUCTION;

EID: 0030025886     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(95)00574-D     Document Type: Article

References (26)

1. (a) Throughout the text, the notation "ras" is used to refer to the gene, whereas, the use of "Ras" refers to the protein product, p21.
2. For leading references dealing with the biology of ras see: (b) Barbacid, M. Annu. Rev. Biochem. 1987, 56, 779.
3. (c) Barbacid, M. Eur. J. Clin. Invest. 1990, 20, 225.
4. (d) Hall, A. Science. 1990, 249, 635.
5. (e) Bourne, H. R.; Sanders, D. A.; McCormick, F. Nature. 1990, 348, 125.
6. For other approaches to non-nucleoside inhibitors of ras see: (a) Noonan, T.; Brown, N.; Dudycz, L.; Wright, G. J. Med. Chem. 1991, 34, 1302.
7. (b) Doll, R. manuscript in preparation, SPRI.
8. For previous work in this area, see: Ganguly, A. K.; Pramanik, B. N.; Tsarbopoulos, A.; Covey, T. R.; Huang, E.; Fuhrman, S. A. J. Am. Chem. Soc. 1992, 114, 6559.
9. For experimental conditions describing the nucleotide exchange assay, see: Hall, A.; Self, A. J. Biol. Chem. 1986, 261, 10963.
10. (a) Radal, S.; Zikan, V. Coll. Czech. Chem. Comm. 1987, 788.
11. (b) Crenshaw, R. R.; Luke, G. M.; Siminoff, P. J. Med. Chem. 1976, 19, 262.
12. Vorbruggen, H.; Krolikiewicz, K.; Bennua, B. Chem. Ber. 1981, 114, 1234.
13. 3) 156.55, 150.05, 149.75, 145.74, 144.30, 142.76, 134.66, 129.55, 125.38, 124.35, 123.19, 122.88, 114.28, 100.59, 79.38, 77.72, 63.57, 57.47, 56.28, 55.68, 15.22. MS, (SIMS) m/e 516.2 (M+1).
14. (a) Grigs, N. S.; Cottam, H. B.; Larson, S. B.; Robins, R. K. Nucleic Acids Res. 1987, 15, 1217.
15. (b) Meade, E. A.; Wotring, L. L.; Drach, J. C.; Townsend, L. B. J. Med. Chem. 1992, 35, 526.
16. 50 = 10 μM), compound 30 (34% inhib), compound 31, (61% inhib).
17. (a) Corey, E. J.; Winter, R. A. E. J. Am. Chem. Soc. 1963, 55, 2677.
18. (b) Corey, E. J.; Hopkins, P. B. Tett. Lett. 1982, 23, 1979.
19. (a) Moffatt, J. G. J. Org. Chem. 1911, 36, 1909.
20. (b) Pfitzner, K. E.; Moffatt, J. G. J. Am. Chem. Soc. 1965, 87, 5661.
21. Zemlicka, J.; Freisler, J. V.; Grasser, R.; Horwitz. J. P. J. Org. Chem. 1973, 38, 990.
22. Jung, M. E.; Castro, C. J. Org. Chem. 1993, 58, 807.
23. Stirchak, E. P.; Summerton, J. E.; Weller, D. Nucleic Acids Res. 1989, 17, 6129.
24. 3CN, see: Acton, E. M.; Tong, G. L.; Mosher, C. W.; Wolgemuth, R. L. J. Med. Chem. 1984, 27, 638.
25. (a) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
26. (b) For an improved procedure describing the preparation of this reagent, see: Ireland, R. E.; Liu, L. J. Org. Chem. 1993, 58, 2899.