Linked Life Data

1324315

Source:http://linkedlifedata.com/resource/pubmed/id/1324315

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1992-9-22
pubmed:abstractText
The synthesis and structure-activity profile of a new class of potent and specific LTA4 hydrolase inhibitors are described. Many compounds of this series of omega-[5-(omega-arylalkyl)-2-thienyl]- and omega-[4-(omega-arylalkyl)phenyl]alkanoic acids were found to be potent in vitro inhibitors of the LTB4 production by porcine leukocytes with IC50 ranging from 1 to 10 microM. The side-chain lengths were critical for an optimal activity. Substitutions on the terminal aromatic ring, in the benzene series, by lipophilic and electron-donating substituents substantially enhanced the LTA4 hydrolase inhibition potency. On the other hand, in the thiophene series, the effect of of such substitutions on the LTA4 hydrolase inhibition was rather small. Functionalization within the carboxylic acid side chain by a carbonyl or by a hydroxyl group led to less potent compounds. A metabolically stable LTA4 hydrolase inhibitor, RP64966, was obtained by insertion of an oxygen atom in the beta-position on the carboxylic acid side chain. After oral administration of RP64966 to rats, a plasma extract was found to display potent inhibition of the LTB4 biosynthesis (40% inhibition at 5 mg/kg, po).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3156-69
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Omega-[(omega-arylalkyl)aryl]alkanoic acids: a new class of specific LTA4 hydrolase inhibitors.
pubmed:affiliation
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Departement de Chimie Pharmaceutique et de Biologie, Vitry sur Seine, France.
pubmed:publicationType
Journal Article, Comparative Study