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Article: New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein
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TitleNew aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein
 
AuthorsLiu, X2
Huang, X2
Lin, W2
Wang, D2
Diao, Y3
Li, H3
Hui, X1
Wang, Y2 1
Xu, A2 1
Wu, D2
Ke, D2
 
Keywordsa-FABP inhibitor
Aromatic substituted pyrazoles
Inflammation related diseases
Inflammatory response
 
Issue Date2011
 
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/bmcl
 
CitationBioorganic And Medicinal Chemistry Letters, 2011, v. 21 n. 10, p. 2949-2952 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.bmcl.2011.03.063
 
Abstracta-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K i value below 1.0 nM, while did not inhibit h-FABP at 50 μM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases. © 2011 Elsevier Ltd. All rights reserved.
 
ISSN0960-894X
2013 Impact Factor: 2.331
 
DOIhttp://dx.doi.org/10.1016/j.bmcl.2011.03.063
 
ISI Accession Number IDWOS:000290024200033
Funding AgencyGrant Number
National Basic Research Program of China2010CB529706
2010CB9455000
2009CB940904
Chinese Academy of Sciences
National Natural Science Foundation30811120429
3097063
90813033
Funding Information:

We thank National Basic Research Program of China (Grant #2010CB529706, 2010CB9455000 and 2009CB940904), the 100-talent program of Chinese Academy of Sciences, and National Natural Science Foundation (Grant #30811120429, 3097063 and 90813033) for their financial support.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLiu, X
 
dc.contributor.authorHuang, X
 
dc.contributor.authorLin, W
 
dc.contributor.authorWang, D
 
dc.contributor.authorDiao, Y
 
dc.contributor.authorLi, H
 
dc.contributor.authorHui, X
 
dc.contributor.authorWang, Y
 
dc.contributor.authorXu, A
 
dc.contributor.authorWu, D
 
dc.contributor.authorKe, D
 
dc.date.accessioned2011-09-23T05:50:09Z
 
dc.date.available2011-09-23T05:50:09Z
 
dc.date.issued2011
 
dc.description.abstracta-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K i value below 1.0 nM, while did not inhibit h-FABP at 50 μM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases. © 2011 Elsevier Ltd. All rights reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationBioorganic And Medicinal Chemistry Letters, 2011, v. 21 n. 10, p. 2949-2952 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.bmcl.2011.03.063
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.bmcl.2011.03.063
 
dc.identifier.eissn1464-3405
 
dc.identifier.epage2952
 
dc.identifier.hkuros194038
 
dc.identifier.isiWOS:000290024200033
Funding AgencyGrant Number
National Basic Research Program of China2010CB529706
2010CB9455000
2009CB940904
Chinese Academy of Sciences
National Natural Science Foundation30811120429
3097063
90813033
Funding Information:

We thank National Basic Research Program of China (Grant #2010CB529706, 2010CB9455000 and 2009CB940904), the 100-talent program of Chinese Academy of Sciences, and National Natural Science Foundation (Grant #30811120429, 3097063 and 90813033) for their financial support.

 
dc.identifier.issn0960-894X
2013 Impact Factor: 2.331
 
dc.identifier.issue10
 
dc.identifier.pmid21481589
 
dc.identifier.scopuseid_2-s2.0-79955561585
 
dc.identifier.spage2949
 
dc.identifier.urihttp://hdl.handle.net/10722/139452
 
dc.identifier.volume21
 
dc.languageeng
 
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/bmcl
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofBioorganic and Medicinal Chemistry Letters
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdipocytes - drug effects
 
dc.subject.meshAnti-Inflammatory Agents - chemical synthesis - chemistry - pharmacology
 
dc.subject.meshDrug Design
 
dc.subject.meshFatty Acid-Binding Proteins - antagonists and inhibitors
 
dc.subject.meshPyrazoles - chemical synthesis - chemistry - pharmacology
 
dc.subjecta-FABP inhibitor
 
dc.subjectAromatic substituted pyrazoles
 
dc.subjectInflammation related diseases
 
dc.subjectInflammatory response
 
dc.titleNew aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein
 
dc.typeArticle
 
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<contributor.author>Wang, D</contributor.author>
<contributor.author>Diao, Y</contributor.author>
<contributor.author>Li, H</contributor.author>
<contributor.author>Hui, X</contributor.author>
<contributor.author>Wang, Y</contributor.author>
<contributor.author>Xu, A</contributor.author>
<contributor.author>Wu, D</contributor.author>
<contributor.author>Ke, D</contributor.author>
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<description.abstract>a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5g bound to a-FABP with an apparent K i value below 1.0 nM, while did not inhibit h-FABP at 50 &#956;M and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases. &#169; 2011 Elsevier Ltd. All rights reserved.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong
  2. Chinese Academy of Sciences
  3. East China University of Science and Technology