Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
16
|
| pubmed:dateCreated |
1996-9-24
|
| pubmed:abstractText |
As part of our research for the development of novel antiinflammatory drug candidates, we have designed and synthesized a series of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)alkyl]-2-propenoic acid derivatives as dual inhibitors of 5-lipoxygenase (5-LO) and thromboxane (TX) A2 synthetase. In order to increase the absorption after oral administration, we introduced a carboxylic acid moiety into the 1,4-benzoquinone skeleton, which has 5-LO-inhibitory character. Introduction of a 3-pyridylalkyl group at the double bond of the 1,4-benzoquinonyl propenoic acid moiety afforded good to moderate inhibitory activities against the production of leukotriene (LT) B4 and TXA2 while not significantly inhibiting that of prostaglandin E2 by glycogen-induced peritoneal cells of rat (in vitro). The length of the methylene chain of the 3-pyridylalkyl group influenced the inhibition of LTB4 and TXB2 production. An increase of lipophilicity by introducing a more lipophilic alkoxy group did not markedly increase the inhibitory activity on LTB4 production. The position of alkoxy group on the 1,4-benzoquinone skeleton played an important role in TXA2 synthetase inhibition. Compounds such as 20c (E6700) with an appropriate alkoxy group and proper length of methylene side chain, together with a polar substituent (carboxylic acid), showed good inhibition of both 5-LO and TXA2 synthetase and possess a variety of pharmacologically beneficial effects.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyurea,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene B4,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Methacrylates,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Thromboxane B2,
http://linkedlifedata.com/resource/pubmed/chemical/Thromboxane-A Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/ozagrel,
http://linkedlifedata.com/resource/pubmed/chemical/zileuton
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
2
|
| pubmed:volume |
39
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3148-57
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:8759636-Animals,
pubmed-meshheading:8759636-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:8759636-Benzoquinones,
pubmed-meshheading:8759636-Blood Platelets,
pubmed-meshheading:8759636-Cells, Cultured,
pubmed-meshheading:8759636-Humans,
pubmed-meshheading:8759636-Hydroxyurea,
pubmed-meshheading:8759636-Leukotriene B4,
pubmed-meshheading:8759636-Lipoxygenase Inhibitors,
pubmed-meshheading:8759636-Magnetic Resonance Spectroscopy,
pubmed-meshheading:8759636-Methacrylates,
pubmed-meshheading:8759636-Molecular Structure,
pubmed-meshheading:8759636-Neutrophils,
pubmed-meshheading:8759636-Pyridines,
pubmed-meshheading:8759636-Rats,
pubmed-meshheading:8759636-Structure-Activity Relationship,
pubmed-meshheading:8759636-Thromboxane B2,
pubmed-meshheading:8759636-Thromboxane-A Synthase
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Structure-activity relationships of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)-alkyl]-2-propenoic acid derivatives that inhibit both 5-lipoxygenase and thromboxane A2 synthetase.
|
| pubmed:affiliation |
Tsukuba Research Laboratories, Eisai Company Ltd., Ibaraki, Japan.
|
| pubmed:publicationType |
Journal Article
|