- Synthesis and biological profile of the pan-vascular endothelial growth factor receptor/tyrosine kinase with immunoglobulin and epidermal growth factor-like homology domains 2 (VEGF-R/TIE-2) inhibitor 11-(2-Methylpropyl)-12, 13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4 H -indazolo[5,4-a]pyrrolo[3,4-c] carbazol-4-one (CEP-11981): A novel oncology therapeutic agent
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A substantial body of evidence supports the utility of antiangiogenesis inhibitors as a strategy to block or attenuate tumor-induced angiogenesis and inhibition of primary and metastatic tumor growth in a variety of solid and hematopoietic tumors. Given the requirement of tumors for different cytokine and growth factors at distinct stages of their growth and dissemination, optimal antiangiogenic therapy necessitates inhibition of multiple, complementary, and nonredundant angiogenic targets. 11-(2-Methylpropyl)-12,13-dihydro-2-methyl-8- (pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (11b, CEP-11981) is a potent orally active inhibitor of multiple targets (TIE-2, VEGF-R1, 2, and 3, and FGF-R1) having essential and nonredundant roles in tumor angiogenesis and vascular maintenance. Outlined in this article are the design strategy, synthesis, and biochemical and pharmacological profile for 11b, which completed Phase I clinical assessing safety and pharmacokinetics allowing for the initiation of proof of concept studies.
- Hudkins, Robert L.,Becknell, Nadine C.,Zulli, Allison L.,Underiner, Ted L.,Angeles, Thelma S.,Aimone, Lisa D.,Albom, Mark S.,Chang, Hong,Miknyoczki, Sheila J.,Hunter, Kathryn,Jones-Bolin, Susan,Zhao, Hugh,Bacon, Edward R.,Mallamo, John P.,Ator, Mark A.,Ruggeri, Bruce A.
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- METHOD FOR PURIFYING A FUSED PYRROLOCARBAZOLE DERIVATIVE
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The present invention relates a method for purifying a fused pyrrolocarbazole compound known as 11-isobutyl-2-methyl-8-(2-pyrimidinylamino)-2,5,6,11,12,13-hexahydro-4Hindazolo[5,4-a]pyrrolo [3,4-c]carbazol-4-one using an acid complex thereof. The present
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- Novel fused pyrrolocarbazoles
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The present invention relates generally to selected fused pyrrolocarbazoles, including pharmaceutical compositions thereof and methods of treating diseases therewith. The present invention is also directed to intermediates and processes for making these f
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(2010/02/12)
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