- SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF
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This invention provides compounds of formula (I): wherein R1, R1b, R2a, R2b, R2c, and R2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.
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- Design and optimization of potent and orally bioavailable tetrahydronaphthalene raf inhibitors
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Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.
- Gould, Alexandra E.,Adams, Ruth,Adhikari, Sharmila,Aertgeerts, Kathleen,Afroze, Roushan,Blackburn, Christopher,Calderwood, Emily F.,Chau, Ryan,Chouitar, Jouhara,Duffey, Matthew O.,England, Dylan B.,Farrer, Cheryl,Forsyth, Nancy,Garcia, Khristofer,Gaulin, Jeffery,Greenspan, Paul D.,Guo, Ribo,Harrison, Sean J.,Huang, Shih-Chung,Iartchouk, Natalia,Janowik, Dave,Kim, Mi-Sook,Kulkarni, Bheemashankar,Langston, Steven P.,Liu, Jane X.,Ma, Li-Ting,Menon, Saurabh,Mizutani, Hirotake,Paske, Erin,Renou, Christelle C.,Rezaei, Mansoureh,Rowland, R. Scott,Sintchak, Michael D.,Smith, Michael D.,Stroud, Stephen G.,Tregay, Ming,Tian, Yuan,Veiby, Ole P.,Vos, Tricia J.,Vyskocil, Stepan,Williams, Juliet,Xu, Tianlin,Yang, Johnny J.,Yano, Jason,Zeng, Hongbo,Zhang, Dong Mei,Zhang, Qin,Galvin, Katherine M.
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p. 1836 - 1846
(2011/05/30)
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- PREPARATION OF AMINOTETRALIN COMPOUNDS
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The present invention relates to synthetic processes for preparation of aminotetralin compounds with kinase inhibitory activity. The invention also provides synthetic intermediates useful in the processes of the invention.
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Page/Page column 12
(2010/08/08)
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