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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2007-8-30
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pubmed:abstractText |
We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the N1 nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the N1 nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:CheungMuiM,
pubmed-author:HarrisPhilip APA,
pubmed-author:HasegawaMasaichiM,
pubmed-author:KanoKazuyaK,
pubmed-author:MoriIchiroI,
pubmed-author:NishigakiNaohikoN,
pubmed-author:NolteRobert TRT,
pubmed-author:SatoHideyukiH,
pubmed-author:ShibaharaMegumiM,
pubmed-author:ToyodaHirokoH,
pubmed-author:VealJames MJM,
pubmed-author:WangLipingL,
pubmed-author:WashioYoshiakiY,
pubmed-author:WestRob IRI
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4453-70
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17676829-Animals,
pubmed-meshheading:17676829-Benzimidazoles,
pubmed-meshheading:17676829-Binding Sites,
pubmed-meshheading:17676829-Crystallography, X-Ray,
pubmed-meshheading:17676829-Humans,
pubmed-meshheading:17676829-Mice,
pubmed-meshheading:17676829-Models, Molecular,
pubmed-meshheading:17676829-Molecular Structure,
pubmed-meshheading:17676829-NIH 3T3 Cells,
pubmed-meshheading:17676829-Phosphorylation,
pubmed-meshheading:17676829-Receptor, TIE-2,
pubmed-meshheading:17676829-Structure-Activity Relationship,
pubmed-meshheading:17676829-Vascular Endothelial Growth Factor Receptor-2
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pubmed:year |
2007
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pubmed:articleTitle |
Discovery of novel benzimidazoles as potent inhibitors of TIE-2 and VEGFR-2 tyrosine kinase receptors.
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pubmed:affiliation |
Tsukuba Research Laboratories, GlaxoSmithKline K.K., 43 Wadai, Tsukuba, Ibaraki 300-4247, Japan. masaichi.hasegawa@gsk.com
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pubmed:publicationType |
Journal Article
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