Linked Life Data

1654427

Source:http://linkedlifedata.com/resource/pubmed/id/1654427

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1991-10-22
pubmed:abstractText
Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists. In the omega-[(phenylmethoxy)phenyl]-omega-oxoalkanoic acid series, 5-[4-[(4-acetyl-2-ethyl-3-hydroxyphenyl)methoxy]phenyl]-3,3-dimethyl-5- oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pKB of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv). Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds. In the omega-[5-[[(phenylmethoxy)phenyl]alkyl] tetrazolyl]alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat. The pKB value in the guinea pig ileum for 1-[2-hydroxy-3-propyl-4- [[4-[[2-[3-(1H-tetrazol-5-yl)propyl]-2H-tetrazol-5-yl]methyl ] phenoxy]methyl]phenyl]ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv. The sodium salts of 8 (9) and 25 (26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner. Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2768-78
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
(Phenylmethoxy)phenyl derivatives of omega-oxo- and omega-tetrazolylalkanoic acids and related tetrazoles. Synthesis and evaluation as leukotriene D4 receptor antagonists.
pubmed:affiliation
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
pubmed:publicationType
Journal Article