Omega-Carboxyaryl Substituted Diphenyl Ureas As Raf Kinase Inhibitors
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a technology of aryl ureas and kinase inhibitors, which is applied in the field of group of aryl ureas in treating raf-mediated diseases, can solve problems such as cell cancer
Inactive Publication Date: 2008-06-26
BAYER HEALTHCARE LLC
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This leads to the cancerous growth of the cells which carry these mutants (Magnuson et al.
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[0052]All reactions were performed in flame-dried or oven-dried glassware under a positive pressure of dry argon or dry nitrogen, and were stirred magnetically unless otherwise indicated. Sensitive liquids and solutions were transferred via syringe or cannula, and introduced into reaction vessels through rubber septa. Unless otherwise stated, the term ‘concentration under reduced pressure’ refers to use of a Buchi rotary evaporator at approximately 15 mmHg. Unless otherwise stated, the term ‘under high vacuum’ refers to a vacuum of 0.4-1.0 mmHg.
[0053]All temperatures are reported uncorrected in degrees Celsius (° C.). Unless otherwise indicated, all parts and percentages are by weight.
[0054]Commercial grade reagents and solvents were used without further purification. N-cyclohexyl-N′-(methylpolystyrene)carbodiimide was purchased from Calbiochem-Novabiochem Corp. 3-tert-Butylaniline, 5-tert-butyl-2-methoxyaniline, 4-bromo-3-(trifluoromethyl)aniline, 4-chloro-3-(trifluoromethyl)anilin...
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Abstract
This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This is a continuation-in-part of Ser. No. 09 / 257,266 filed Feb. 25, 1999 and a continuation-in-part of Ser. No. 60 / 115,877 filed Jan. 13, 1999.FIELD OF THE INVENTION[0002]This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.BACKGROUND OF THE INVENTION[0003]The p21ras oncogene is a major contributor to the development and progression of human solid cancers and is mutated in 30% of all human cancers (Bolton et al. Ann. Rep. Med. Chem. 1994, 29, 165-74; Bos. Cancer Res. 1989, 49, 4682-9). In its normal, unmutated form, the ras protein is a key element of the signal transduction cascade directed by growth factor receptors in almost all tissues (Avruch et al. Trends Biochem. Sci. 1994, 19, 279-83). Biochemically, ras is a guanine nucleotide binding protein, and cycling between a GTP-bound activated and a GDP-bound resting form is strictly controll...
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