|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0054858,
umls-concept:C0070829,
umls-concept:C0205103,
umls-concept:C0205332,
umls-concept:C0205360,
umls-concept:C0243077,
umls-concept:C0311400,
umls-concept:C0332256,
umls-concept:C1167622,
umls-concept:C1272745,
umls-concept:C1511539,
umls-concept:C1522492,
umls-concept:C1708528
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|
pubmed:issue |
16
|
|
pubmed:dateCreated |
2002-7-19
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|
pubmed:abstractText |
A detailed study directed towards metabolic stability optimization of the alkoxy substituents on the catechol moiety of CDP-840 is reported. Replacement of the methoxy and cyclopentyloxy substituents by cyclobutyloxy and/or difluromethoxy groups resulted in the discovery of potent and selective PDE4 inhibitors where the formation of reactive metabolites that could covalently bind to microsomal protein was significantly reduced or eliminated.
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pubmed:language |
eng
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pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0960-894X
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|
pubmed:author |
|
|
pubmed:issnType |
Print
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pubmed:day |
19
|
|
pubmed:volume |
12
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
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pubmed:pagination |
2149-52
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|
pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12127525-3',5'-Cyclic-AMP Phosphodiesterases,
pubmed-meshheading:12127525-Animals,
pubmed-meshheading:12127525-Catechols,
pubmed-meshheading:12127525-Cyclic Nucleotide Phosphodiesterases, Type 4,
pubmed-meshheading:12127525-Microsomes, Liver,
pubmed-meshheading:12127525-Molecular Structure,
pubmed-meshheading:12127525-Protein Binding,
pubmed-meshheading:12127525-Pyridines,
pubmed-meshheading:12127525-Rats,
pubmed-meshheading:12127525-Structure-Activity Relationship
|
|
pubmed:year |
2002
|
|
pubmed:articleTitle |
Improving metabolic stability of phosphodiesterase-4 inhibitors containing a substituted catechol: prevention of reactive intermediate formation and covalent binding.
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|
pubmed:affiliation |
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, H9R 4P8, Québec, Canada. nathalie_chauret@merk.com
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pubmed:publicationType |
Journal Article
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