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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2007-6-18
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pubmed:abstractText |
Benzimidazole 1 was identified as a selective inhibitor of ITK by high throughput screening. Hit-to-lead studies defined the SAR at all three substituents. Reversing the amide linkage at C6 led to 16, with a fivefold improvement of potency. This enhancement is rationalized by the conformational preference of the substituent. A model for the binding of the benzimidazoles to the ATP-binding site of ITK is proposed.
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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 |
Jul
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:AbeywardaneAsithaA,
pubmed-author:CampbellScotS,
pubmed-author:CywinCharles LCL,
pubmed-author:KashemMohammed AMA,
pubmed-author:KhineHnin HninHH,
pubmed-author:KingJosephineJ,
pubmed-author:KowalskiJennifer AJA,
pubmed-author:LordJohnJ,
pubmed-author:PullenSteven SSS,
pubmed-author:RomaTeresaT,
pubmed-author:RothGregory PGP,
pubmed-author:SarkoChristopher RCR,
pubmed-author:SnowRoger JRJ,
pubmed-author:WilsonNoel SNS,
pubmed-author:WintersMichael PMP,
pubmed-author:WolakJohn PJP
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3660-5
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17499505-Adenosine Triphosphate,
pubmed-meshheading:17499505-Benzimidazoles,
pubmed-meshheading:17499505-Binding Sites,
pubmed-meshheading:17499505-Chemistry, Pharmaceutical,
pubmed-meshheading:17499505-Drug Evaluation, Preclinical,
pubmed-meshheading:17499505-Enzyme Inhibitors,
pubmed-meshheading:17499505-Humans,
pubmed-meshheading:17499505-Hydrogen Bonding,
pubmed-meshheading:17499505-Inhibitory Concentration 50,
pubmed-meshheading:17499505-Models, Chemical,
pubmed-meshheading:17499505-Protein Binding,
pubmed-meshheading:17499505-Protein Kinase Inhibitors,
pubmed-meshheading:17499505-Protein-Tyrosine Kinases,
pubmed-meshheading:17499505-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
Hit-to-lead studies on benzimidazole inhibitors of ITK: discovery of a novel class of kinase inhibitors.
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pubmed:affiliation |
Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA. rsnow@rdg.boehringer-ingelheim.com <rsnow@rdg.boehringer-ingelheim.com>
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pubmed:publicationType |
Journal Article
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