Linked Life Data

9341913

Source:http://linkedlifedata.com/resource/pubmed/id/9341913

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1997-11-28
pubmed:abstractText
Derivatives of 3-(1,3,5-trimethyl-4-octadecanoylpyrrol-2-yl)propionic acid (1) and (1,3,5-trimethyl-4-octadecanoylpyrrol-2-yl)acetic acid (4) were prepared and evaluated for their ability to inhibit the cytosolic phospholipase A2 of intact bovine platelets. While replacement of one of the methyl groups in position 1, 3, or 5 of the acetic acid 4 by a benzyl residue did not influence the inhibitory potency significantly, the introduction of a dodecyl chain led to compounds which even enhanced the enzymatic activity. Stepwise elongation of the alkyl substituent in position 1 showed that the ability to inhibit the enzyme was lost when the alkyl chain exceeded a length of five carbons in case of compound 1 or six carbons in case of compound 4. Introduction of a polar functional group at the end of the 1-alkyl chain of these inactive pyrroles, however, restored or even elevated inhibitory potency. The most preferable of the polar terminal functions investigated was the carboxylic acid moiety. 6-[2-(2-Carboxyethyl)-4-dodecanoyl-3,5-dimethylpyrrol-1-yl]hexanoi c acid (65c) and 6-[2-(carboxymethyl)-4-dodecanoyl-3,5-dimethylpyrrol-1-yl]nonanoic acid (66f) were the synthesized inhibitors with the greatest potency. With IC50 values of 3.4 and 3.3 microM, respectively, they were about 3-fold more active than the standard cPLA2 inhibitor arachidonyl trifluoromethyl ketone (IC50: 11 microM).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3381-92
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Structure-activity relationships of (4-acylpyrrol-2-yl)alkanoic acids as inhibitors of the cytosolic phospholipase A2: variation of the substituents in positions 1, 3, and 5.
pubmed:affiliation
Institute of Pharmacy and Food Chemistry, Ludwig-Maximilians-University, Munich, Germany.
pubmed:publicationType
Journal Article