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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2009-9-14
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pubmed:abstractText |
Distinct from previously reported urea and amide inhibitors of soluble epoxide hydrolase (sEH), a novel class of inhibitors were rationally designed based on the X-ray structure of this enzyme and known amide inhibitors. The structure-activity relationship (SAR) study was focused on improving the sEH inhibitory activity. Aminobenzisoxazoles emerged to be the optimal series, of which a potent human sEH inhibitor 7t was identified with a good pharmacokinetics (PK) profile. The strategy of employing aminoheterocycles as amide replacements may represent a general approach to develop mimics of known hydrolase or protease inhibitors containing an amide moiety.
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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 |
Oct
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:Alonso-GaliciaMagdalenaM,
pubmed-author:BergerJoel PJP,
pubmed-author:ChenYuliY,
pubmed-author:CollettiSteven LSL,
pubmed-author:DengQiaolinQ,
pubmed-author:DingFa-XiangFX,
pubmed-author:PaiLee-YuhLY,
pubmed-author:RoySophieS,
pubmed-author:ShenHong CHC,
pubmed-author:TataJames RJR,
pubmed-author:TongXinchunX,
pubmed-author:XuSuoyuS,
pubmed-author:ZhangBeiB,
pubmed-author:ZhangXiaopingX,
pubmed-author:ZhouGaochaoG
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5716-21
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pubmed:meshHeading |
pubmed-meshheading:19700315-Amides,
pubmed-meshheading:19700315-Aniline Compounds,
pubmed-meshheading:19700315-Animals,
pubmed-meshheading:19700315-Binding Sites,
pubmed-meshheading:19700315-Computer Simulation,
pubmed-meshheading:19700315-Enzyme Inhibitors,
pubmed-meshheading:19700315-Epoxide Hydrolases,
pubmed-meshheading:19700315-Heterocyclic Compounds, 2-Ring,
pubmed-meshheading:19700315-Humans,
pubmed-meshheading:19700315-Isoxazoles,
pubmed-meshheading:19700315-Protein Binding,
pubmed-meshheading:19700315-Rats,
pubmed-meshheading:19700315-Structure-Activity Relationship
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pubmed:year |
2009
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pubmed:articleTitle |
A strategy of employing aminoheterocycles as amide mimics to identify novel, potent and bioavailable soluble epoxide hydrolase inhibitors.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. hong_shen@merck.com
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pubmed:publicationType |
Journal Article
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