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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2009-1-27
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pubmed:abstractText |
This Letter describes the synthesis and SAR of two mGluR4 positive allosteric modulator leads, 6 and 7. VU001171 (6) represents the most potent (EC(50)=650 nM), efficacious (141% Glu Max) and largest fold shift (36-fold) of any mGluR4 PAM reported to date. However, this work highlights the challenges in hit-to-lead for mGluR4 PAMs, with multiple confirmed HTS hits displaying little or no tractable SAR.
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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 |
Feb
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pubmed:issn |
1464-3405
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pubmed:author |
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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 |
962-6
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pubmed:meshHeading |
pubmed-meshheading:19097893-Allosteric Regulation,
pubmed-meshheading:19097893-Allosteric Site,
pubmed-meshheading:19097893-Animals,
pubmed-meshheading:19097893-CHO Cells,
pubmed-meshheading:19097893-Chemistry, Pharmaceutical,
pubmed-meshheading:19097893-Cricetinae,
pubmed-meshheading:19097893-Cricetulus,
pubmed-meshheading:19097893-Dose-Response Relationship, Drug,
pubmed-meshheading:19097893-Drug Design,
pubmed-meshheading:19097893-Drug Evaluation, Preclinical,
pubmed-meshheading:19097893-Models, Chemical,
pubmed-meshheading:19097893-Molecular Conformation,
pubmed-meshheading:19097893-Receptors, Metabotropic Glutamate,
pubmed-meshheading:19097893-Structure-Activity Relationship
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pubmed:year |
2009
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pubmed:articleTitle |
Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead.
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pubmed:affiliation |
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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