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rdf:type |
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lifeskim:mentions |
umls-concept:C0205250,
umls-concept:C0205314,
umls-concept:C0205460,
umls-concept:C0220781,
umls-concept:C0220825,
umls-concept:C0243077,
umls-concept:C0679622,
umls-concept:C1150587,
umls-concept:C1367731,
umls-concept:C1705632,
umls-concept:C1880355,
umls-concept:C1883254
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pubmed:issue |
8
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pubmed:dateCreated |
2008-4-24
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pubmed:abstractText |
A novel series of 4-phenylisoquinolones were synthesized and evaluated as c-Jun N-terminal kinase (JNK) inhibitors. Initial modification at the 2- and 3-positions of the isoquinolone ring of hit compound 4, identified from high-throughput screening, led to the lead compound 6b. The optimization was carried out using a JNK1-binding model of 6b and several compounds exhibited potent JNK inhibition. Among them, 11g significantly inhibited cardiac hypertrophy in rat pressure-overload models without affecting blood pressure and the concept of JNK inhibitors as novel therapeutic agents for heart failure was confirmed.
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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 |
Apr
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pubmed:issn |
1464-3391
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pubmed:author |
pubmed-author:AsanoYasutomiY,
pubmed-author:AsoKazuyoshiK,
pubmed-author:ItohFumioF,
pubmed-author:JudsonII,
pubmed-author:KawamotoTomohiroT,
pubmed-author:KimuraHiroyukiH,
pubmed-author:KitamuraShujiS,
pubmed-author:MatsumotoShin-ichiS,
pubmed-author:OhraTaiichiT,
pubmed-author:SogabeSatoshiS,
pubmed-author:TamuraTomokoT,
pubmed-author:TanakaToshimasaT,
pubmed-author:YamaguchiMasashiM
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pubmed:issnType |
Electronic
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pubmed:day |
15
|
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pubmed:volume |
16
|
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pubmed:owner |
NLM
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|
pubmed:authorsComplete |
Y
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pubmed:pagination |
4715-32
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18313304-Animals,
pubmed-meshheading:18313304-Cell Line,
pubmed-meshheading:18313304-Crystallography, X-Ray,
pubmed-meshheading:18313304-Enzyme Activation,
pubmed-meshheading:18313304-Enzyme Inhibitors,
pubmed-meshheading:18313304-Isoquinolines,
pubmed-meshheading:18313304-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:18313304-Male,
pubmed-meshheading:18313304-Models, Molecular,
pubmed-meshheading:18313304-Molecular Structure,
pubmed-meshheading:18313304-Rats,
pubmed-meshheading:18313304-Rats, Wistar,
pubmed-meshheading:18313304-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1).
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pubmed:affiliation |
Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd, 17-85, Jusohonmachi 2-chome, Osaka 532-8686, Japan. Asano_Yasutomi@takeda.co.jp
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pubmed:publicationType |
Journal Article
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