Linked Life Data

1829486

Source:http://linkedlifedata.com/resource/pubmed/id/1829486

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1991-8-6
pubmed:abstractText
S-145, (+/-)-(5Z)-7-[3-endo-[(phenylsulfonyl)amino]bicyclo[2.2.1] heptenoic acid, its chain analogues HO2C(CH2)nNHSO2Ph (n = 3-8, 10, and 11) 1-8, and (5Z)-9-(phenylsulfonyl) aminonon-5-enoic acid (9) were synthesized in order to elucidate the dependence of the conformation in solution and of the pharmacological activity on the side-chain length. Their FTIR spectra were measured in dilute CCl4 solution. For these compounds, intramolecular hydrogen bonds similar to those observed for S-145 were found between the carboxyl and sulfonamido groups. A linear relationship was also found between the percentage (rho) of the intramolecular hydrogen-bonded molecules and the n value. Compounds 1-9 were examined in vitro for inhibitory concentrations (IC50) against U-46619- and collagen-induced aggregations for rabbit and rat washed platelets (WP), respectively, and U-46619-induced contraction for rat aorta. Three kinds of TXA2 receptor antagonistic potencies [log(1/IC50)] showed parabolic correlations with the n value, though the rho value was in direct proportion to the n value. The log (1/IC50) values for 6 (n = 8), which forms a 12-membered ring similar to the one observed for S-145, were found to be maximal values in 1-8 and were comparable to those for BM-13177. In compounds 9 (rho = 83%) and S-145 (rho = 89%), the IC50 values of 41 and 2.9 nM for rat WP were 10 and 141 times lower than that of 6 (rho = 52%), respectively. In these compounds, which form the 12-membered ring, the inhibitory potencies increase as the rho value increases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1885-91
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor antagonist S-145 and related compounds. 3. Conformation and activity of S-145 analogues.
pubmed:affiliation
Shionogi Research Laboratories, Shionogi & Company, Ltd., Osaka, Japan.
pubmed:publicationType
Journal Article