Linked Life Data

8387599

Source:http://linkedlifedata.com/resource/pubmed/id/8387599

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1993-6-9
pubmed:abstractText
Synthetic analogs of the natural product griseolic acid in which a guanine base is substituted for the adenine have been prepared. The best of these compounds inhibits a cyclic guanosine 3',5'-monophosphate (cGMP) phosphodiesterase preparation with an IC50 of 0.34 microM but is a very weak inhibitor of a cyclic adenosine 3',5'-monophosphate (cAMP) phosphodiesterase. An exploration of stereochemistry indicates that the configuration of the carboxylic acids and the ring fusion in the inhibitors is important for potent cGMP PDE inhibition. PDE inhibition is not sensitive to the presence of the 2' or 4' oxygen atoms in the ribose, but inhibition is decreased when the 3' oxygen is removed. A selected group of analogs in which a monocarboxylic acid is present are poor inhibitors. The structure-activity relationship is consistent with the carboxylic acid functionality acting as a mimetic for the phosphate anion in cGMP. This concept is supported by a conformational analysis of two of the inhibitors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1210-20
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Synthesis and phosphodiesterase activity of carboxylic acid mimetics of cyclic guanosine 3',5'-monophosphate.
pubmed:affiliation
Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
pubmed:publicationType
Journal Article, Comparative Study