Bis-aryl ethers, compositions containing such compounds and meth

Details Bis-aryl ethers, compositions containing such compounds and meth Bis-aryl ethers, compositions containing such compounds and meth

1998-07-02

1999-11-30

Gerstl, Robert

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ether doai

568637, 435156, A01N 3114

Patent

active

059944129

ABSTRACT:
A compound represented by the formula I is disclosed: ##STR1## or a pharmaceutically acceptable salt or hydrate thereof. The compound has inhibitory activity against the oncoprotein Raf.
Also included are pharmaceutical compositions, methods of treating cancer, cultures of the producing fungal microorganism and methods of fermentative production of the compound.

REFERENCES:
Barton J chem Soc 1958 p. 1767, 1958.
Hassal Jchem Soc 1959 p. 2831, 1959.
Daum, G. et al., "The ins and outs of Raf kinases," Trends Biochem, Sci., 19, pp. 474-480 (1994).
Kizaka-Kondoh, S. et al., "Raf-1 Protein Kinase Is an Integral Component of the Oncogenic Signal Cascade Shared by Epidermal Growth Factor and Platelet-Derived Growth Factor," Mol. and Cellular Biol., vol. 12, No. 11, pp. 5078-5086 (1992).
Marshall, M., "Interactions Between Ras and Raf: Key Regulatory Proteins in Cellular Transformation," Molecular Reproduction and Development, vol. 42, pp. 493-499 (1995).
Schaap, D. et al., "A Dominant-negative Mutant of raf Blocks Mitogen-activated Protein Kinase Activation by Growth Factors and Oncogenic p21ras*," The Jour. of Biol. Chem., vol. 268, No. 27, pp. 20232-20236 (1993).
White, M. A. et al., "Multiple Ras Functions Can Contribute to Mammalian Cell Transformation," Cell, vol. 80, pp. 533-541 (1995).
Williams, N.G. and Roberts, T.M., "Signal transduction pathways involving the Raf proto-oncogene," Cancer and Metastasis Reviews, vol. 13, No. 1, pp. 105-116 (1994).

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