Novel non-peptide lead structures for Bradykinin B2-receptor antagonists

被引：0

作者：

Pineda L.F. ^{[1
,4
]}

Liebmann C. ^{[1
]}

Hensellek S. ^{[1
]}

Paegelow I. ^{[2
]}

Steinmetzer T. ^{[1
]}

Schweinitz A. ^{[1
]}

Stürzebecher J. ^{[3
]}

Reissmann S. ^{[1
]}

机构：

[1] Inst. of Biochemistry and Biophysics, Faculty of Biology and Pharmacology, Friedrich-Schiller Univ. of Jena, D-07743 Jena

[2] Inst. Exp. Clin. Pharmacol. Toxicol., University of Rostock, D-18057 Rostock

[3] Ctr. for Vasc. Biology and Medicine, Clin. Friedrich-Schiller Univ. Jena, D-99089 Erfurt

[4] Inst. für Molec. Biotech. e.V., D-07708 Jena

来源：

Letters in Peptide Science | 2000年 / 7卷 / 2期

关键词：

3D-pharmacophore mode; Guinea pig ileum; IMR-90; Peptide hormones; Radioligand binding assay;

D O I：

10.1023/A:1008954812407

中图分类号：

学科分类号：

摘要：

A series of new non-peptide Bradykinin (BK) B2-receptor antagonists is reported. These new leads belong to a larger set including both commercially or otherwise available potential candidates found by proprietary database searches using 3D-pharmacophore models as query, and several bis-benzamidino compounds selected from our tryptase-like protease inhibitor library on the basis of topological considerations, derived from the same models. Some of these compounds show functional competitive antagonistic activity, inhibiting in vitro the BK-induced contraction of isolated guinea-pig ileum (GPI) and rat uterus with a pA2 up to 5.3 and 7.0, respectively. They display also binding affinity (IC50 up to 0.56 μM) to the BK B2-receptor in radioligand binding assays on GPI membrane preparations and on human IMR-90 fetal lung fibroblast cells expressing this receptor subtype. Furthermore, the results with the commercially available compounds, in some cases developed as therapeutics, show that the used 3D-pharmacophore model allows to predict to some certainty possible side actions of potential drugs.

引用

页码：69 / 77

页数：8