ISSN:
1573-3904
Keywords:
3D-pharmacophore model
;
guinea pig ileum
;
IMR-90
;
peptide hormones
;
radioligand binding assay
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract A series of new non-peptide Bradykinin (BK)B2-receptor antagonists is reported. These newleads belong to a larger set including bothcommercially or otherwise available potentialcandidates found by proprietary database searchesusing 3D-pharmacophore models as query, and severalbis-benzamidino compounds selected from ourtryptase-like protease inhibitor library on thebasis of topological considerations, derived fromthe same models.Some of these compounds show functional competitiveantagonistic activity, inhibiting {in vitro} the BK-induced contraction of isolated guinea-pig ileum(GPI) and rat uterus with a pA2 up to 5.3 and7.0, respectively. They display also bindingaffinity (IC50 up to 0.56 μM) to the BKB2-receptor in radioligand binding assays onGPI membrane preparations and on human IMR-90 fetallung fibroblast cells expressing this receptor subtype.Furthermore, the results with the commerciallyavailable compounds, in some cases developed astherapeutics, show that the used 3D-pharmacophoremodel allows to predict to some certainty possibleside actions of potential drugs.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008954812407
Permalink
