Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1996-8-23
pubmed:abstractText
Continuing studies on modifications of potent cyclic pentapeptide endothelin (ET) receptor antagonists, represented by BQ-123, and potent linear tripeptide derivative ET receptor antagonists, represented by BQ-788, are described herein. The introduction of D-tryptophan analogues with C-2 substituents in these peptidic ET antagonists resulted in potent ET receptor antagonists with various ETA/ETB subtype selectivity. Combined ETA/ETB receptor antagonists were found in both cyclic pentapeptide and linear tripeptide series with 2-halo- and 2-methyl-D-tryptophans. In contrast, compounds with 2-cyano-D-tryptophan were ETB receptor-selective antagonists. The C-2 substituent of the D-tryptophanyl residue appeared to be very important for the discrimination of ETA/ETB subtype selectivity of the antagonists. The potent ET receptor antagonists with various ETA/ETB subtype selectivity synthesized in this study may be useful tools for elucidating the physiological and pathophysiological roles of ET and ET receptors.
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:day
7
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2313-30
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Synthesis and structure-activity relationships of 2-substituted D-tryptophan-containing peptidic endothelin receptor antagonists: importance of the C-2 substituent of the D-tryptophan residue for endothelin A and B receptor subtype selectivity.
pubmed:affiliation
Drug Discovery Research Laboratories, Tsukuba Research Institute, Banyu Pharmaceutical Company, Ltd., Ibaraki, Japan.
pubmed:publicationType
Journal Article, Comparative Study