Linked Life Data

8464032

Source:http://linkedlifedata.com/resource/pubmed/id/8464032

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1993-4-30
pubmed:abstractText
A series of novel azulene-1 carboxylic acid derivatives 28-30, azulene-1 sulfonic acid sodium salts 41a-c, and related compounds were synthesized. These compounds were tested for TXA2 receptor antagonistic activity. The inhibitory concentrations (IC50) of these compounds for vascular contraction (TXA2 tau receptor) and platelet aggregation (TXA2 alpha receptor) induced by (15S)-15-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5(Z),13(E)- dienoic acid (U-46619) were obtained. Azulene-1-sulfonic acid sodium salts 41a-c were over 3 times more potent than azulene-1-carboxylic acids 28-30. The most potent compound, 41b was 4 orders of magnitude more potent than a TXA2 antagonist, BM13,177, in inhibiting vascular contraction (tau receptor) and had an IC50 of 9.0 x 10(-10) M. Compound 41b was also found to be a tau receptor selective antagonist (IC50 of contraction/IC50 of aggregation = 378) and to have no TXA2 synthetase inhibitory activity at concentrations up to 10(-4) M and no partial agonistic activity at concentrations up to 10(-5) M in rabbit aorta (tau receptor) and up to 10(-4) M in rabbit platelet-rich plasma (alpha receptor). In a radioligand binding assay using rabbit gel-filtered platelets, compound 41b had a high-affinity binding for the TXA2 receptor. In an in vivo study, compound 41b inhibited U-46619-induced sudden death in mice at a dose of 0.3 mg/kg and its duration of action was over 8 h when administered orally at 3 mg/kg.
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
2
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
791-800
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Design, synthesis, and pharmacology of 3-substituted sodium azulene-1-sulfonates and related compounds: non-prostanoid thromboxane A2 receptor antagonists.
pubmed:affiliation
Kotobuki Research Laboratories, Kotobuki Seiyaku Company, Ltd., Nagano, Japan.
pubmed:publicationType
Journal Article