- Urea derivatives of STI571 as inhibitors of Bcr-Abl and PDGFR kinases
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Urea-based analogues of STI571 are described possessing structural features which can differentiate between Abl/Bcr-Abl and PDGFR kinase inhibition. The constitutively active Abl kinase activity of the Bcr-Abl oncoprotein is causative for chronic myelogenous leukemia. Urea derivatives, structurally related to the therapeutic agent STI571, have been identified, which potently inhibit the tyrosine kinase activity of recombinant Abl. In particular a dimethylamino-aniline derivative (18) inhibited c-Abl transphosphorylation with an IC50 value of 56 nM. Although this activity was not translated into cellular activity against the constitutively activated oncogenic Bcr-Abl, a number of compounds from this series potently inhibited cellular PDGFR autophosphorylation. It was also possible to differentiate between c-Abl and PDGFR kinase inhibition, with compound 22 being selective towards Abl and 23 selective for PDGFR.
- Manley, Paul W.,Breitenstein, Werner,Brüggen, Josef,Cowan-Jacob, Sandra W.,Furet, Pascal,Mestan, Jürgen,Meyer, Thomas
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p. 5793 - 5797
(2007/10/03)
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- 2-AMINOPYRIMIDINE DERIVATIVES AS RAF KINASE INHIBITORS
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This application discloses compounds that inhibit Raf kinase having the formula (I), wherein R1 is a phenyl radical or a heteroaryl radical; and R2 is a phenyl radical; or an N-oxide or a pharmaceutically acceptable salt thereof. The compounds are useful for the treatment of proliferative diseases, such as cancer.
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Page/Page column 24
(2010/02/09)
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