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rdf:type |
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lifeskim:mentions |
umls-concept:C0031809,
umls-concept:C0201734,
umls-concept:C0205265,
umls-concept:C0205314,
umls-concept:C0220847,
umls-concept:C0243077,
umls-concept:C0679622,
umls-concept:C1335439,
umls-concept:C1441547,
umls-concept:C1555582,
umls-concept:C2698650
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pubmed:issue |
11
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pubmed:dateCreated |
2008-5-30
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pubmed:abstractText |
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. Lead optimization led to the discovery of compound 3a, which displayed potent inhibitory activities in biochemical and replicon assays [IC(50) (1b)<10nM; IC(50) (1a)=22 nM; EC(50) (1b)=5nM], good stability toward human liver microsomes (HLM t(1/2)>60 min), and high ratios of liver to plasma concentrations 12h after a single oral administration to rats.
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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 |
Jun
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:AyidaBenjaminB,
pubmed-author:BartkowskiDarian MDM,
pubmed-author:BertoliniThomasT,
pubmed-author:BrooksJenniferJ,
pubmed-author:DragovichPeter SPS,
pubmed-author:KamranRuhiR,
pubmed-author:KirkovskyLeoL,
pubmed-author:KissingerCharles RCR,
pubmed-author:LebrunLaurie ALA,
pubmed-author:LiLian-ShengLS,
pubmed-author:MurphyDouglas EDE,
pubmed-author:NolanThomas GTG,
pubmed-author:NorrisDaniel ADA,
pubmed-author:PatelRupalR,
pubmed-author:RuebsamFrankF,
pubmed-author:SergeevaMaria VMV,
pubmed-author:ShahAmit MAM,
pubmed-author:ShowalterRichard ERE,
pubmed-author:StankovicNebojsaN,
pubmed-author:SunZhongxiangZ,
pubmed-author:TranChinh VCV,
pubmed-author:TsanMeiM,
pubmed-author:WebberStephen ESE,
pubmed-author:ZhaoJingjingJ,
pubmed-author:ZhaoQiangQ,
pubmed-author:ZhouYuefenY
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|
pubmed:issnType |
Electronic
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pubmed:day |
1
|
|
pubmed:volume |
18
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
3446-55
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pubmed:meshHeading |
pubmed-meshheading:18457949-Administration, Oral,
pubmed-meshheading:18457949-Animals,
pubmed-meshheading:18457949-Antiviral Agents,
pubmed-meshheading:18457949-Combinatorial Chemistry Techniques,
pubmed-meshheading:18457949-Drug Design,
pubmed-meshheading:18457949-Hepacivirus,
pubmed-meshheading:18457949-Humans,
pubmed-meshheading:18457949-Microsomes, Liver,
pubmed-meshheading:18457949-Molecular Structure,
pubmed-meshheading:18457949-Pyridazines,
pubmed-meshheading:18457949-RNA Replicase,
pubmed-meshheading:18457949-Rats,
pubmed-meshheading:18457949-Structure-Activity Relationship,
pubmed-meshheading:18457949-Viral Nonstructural Proteins
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pubmed:year |
2008
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pubmed:articleTitle |
Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 3: Further optimization of the 2-, 6-, and 7'-substituents and initial pharmacokinetic assessments.
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pubmed:affiliation |
Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.
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pubmed:publicationType |
Journal Article
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