MEDI 373 |
| Angiogenesis is not only a dynamic and very complex process that involves the formation of new blood vessels from the existing vasculature but is also a critical process during early embryonic development as well as in a number of processes including cancer, rheumatoid arthritis and psoriasis. The development of the normal vasculature is believed to be dependent on the vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases, mainly VEGF-R2 and the angiopoietins (Ang-1 and Ang-2) and its receptor kinases, primarily TIE-2. Thus, the disruption of both VEGF-R2 and TIE-2 receptor signaling are an attractive targets to prevent tumor angiogenesis, which can then lead to the inhibition of tumor growth and metastasis. We have identified dihydroindazolocarbazole based oximes as low nanomolar potent dual VEGF-R2 and TIE-2 receptor tyrosine kinase inhibitors. We will present in detail the structure-activity relationships (SAR), pharmacokinetic, and the in vivo evaluation of lead dihydroindazolocarbazole oximes. |
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Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |