KDR kinase inhibitor

Y. Xu, L. Du, E. D. Soli, M. P. Braun, D. C. Dean, and D. G. Musson, Simultaneous determination of a novel KDR kinase inhibitor and its N-oxide metabolite in human plasma using 96-well solid-phase extraction and liquid chromatography/ tandem mass spectrometry, /. Chromatogr. B 817 (2005), 287-296. 

Several other groups have reported the synthesis and Suzuki reactions of an N-methylindolyl-3-carboxamido-2-boronic acid for the synthesis of benzo[a]carbazoles [128], an iV-Boc-5-sulfonamidoindolyl-2-boronic acid for the synthesis of novel KDR kinase inhibitors [129], indolyl-4-boronic acid in a new synthesis of lysergic acid [130], and 5-, 6-, and 7-indolylboronic acids for the synthesis of aryl-substituted indoles [131]. Carbazole-2,7-bis (boronates) have been employed to construct diindolocaibazoles [132]. 

Related Pd-cyclizations have been applied to the synthesis of 3-carboethoxy-2-trifluoromethylindoles [329], 2-carbobenzyloxy-4-hydroxymethyl-3-methylindoles, a unit that is present in the antibiotic nosiheptide, from a 2-(2-iodoanilino) unsaturated ester [330], 2- and 3-indolecarboxylates on solid phase [331], stephacidin A [332], an indolylquinoline KDR kinase inhibitor [333], tricyclic indoles from (2-iodophenyl)alkyl allenes [334], and 3-cyanoindoles [335], A nice vaiiation utilizes the in situ synthesis of 2-iodoanilino enamines and subsequent cyclization as shown for the preparation of indoles 322 [336],... 

The Sonogashira coupling was applied to the synthesis of an indole-containing KDR kinase inhibitor by tandem Sonogashira coupling/5-ew[Pg.99]

Small Molecular Weight Tyrosine Kinase Inhibitors to KDR. 342... 

As of today, Cediranib (AZD2171) has the potential to be a best in class angiogenesis therapy. It is one of a new generation series of orally available, highly potent inhibitors of KDR kinase. The compound inhibited VEGF-stimulated HUVEC cell proliferation with an IC50 value of 0.4 nM and was specific for this type of proliferation. 

Merck Co (West Point, PA, www.merck.com) is developing L21649, a small molecular weight KDR and KDR/Flt3 kinase inhibitor for the potential treat-... 

Amino-3-aroylthieno[2,3-f]pytidines have been synthesized for their potential to serve as allosteric enhancers at the adenosine Aj receptor <2006BML5530>. Thieno[3,2-f]pyridine derivatives have been found to be potent Lck inhibitors that are highly selective within the Src-family of tyrosine kinases <2007BML1167>. Thieno[3,2-f]pyridine urea compounds have been shown to be potent inhibitors of KDR kinase <2007BML1246>. Thieno[2,3-/ ]pyridine-... 

Stewart, K. Kinase Inhibitor Design Introduction and Examples from KDR, CHK, and PIM Kinases. Presented at Medicinal Biochemistry Symposium, University of North Carolina at Greensboro, Greensboro, NC, April 2009. 

Figure 10.22 In vitro KDR kinase inhibitory activity and hERG binding data as determined in a radioligand binding assay for three compounds. (Dinges, J., et al. l,4-dihydroindeno[l,2-c]pyrazoles with acetylenic side chains as novel and potent multitargeled receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel. J. Med. Chem. 2007, 50, 2011-2029.)...

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