Novel inhibitors of the sodium–calcium exchanger: benzene ring analogues of N-guanidino substituted amiloride derivatives
| Autor: | F. Rogister, Carine Maggetto, Jacques Delarge, Bernard Masereel, Marianne Ghyoot, Françoise Van Eylen, Jean-François Liégeois, André Herchuelz, Didier Laeckmann, P O Plasman, Joseph Géczy |
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| Rok vydání: | 2001 |
| Předmět: |
Blood Platelets
Pyrazine Stereochemistry Sodium chemistry.chemical_element Calcium Guanidines Chemical synthesis Sodium-Calcium Exchanger Amiloride Inhibitory Concentration 50 chemistry.chemical_compound Drug Discovery Tumor Cells Cultured medicine Animals Humans Diuretics Guanidine Pharmacology HEPES Sodium-calcium exchanger Calcium Radioisotopes Organic Chemistry Benzene General Medicine Rats chemistry Insulinoma medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 36:597-614 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/s0223-5234(01)01247-8 |
| Popis: | A series of N-guanidino substituted 2,4-diamino-5-carbonylguanidine molecules related to amiloride were synthesised and evaluated for their ability to inhibit the sodium-calcium exchanger in rat insulinoma cells (RINm5F) and human platelets. Specific chemical pathways were used to prepare the benzene derivatives designed as bioisosteric analogues of the pyrazine derivatives of amiloride. Several so-called 'simplified analogues', where some substituents of amiloride were omitted or replaced, were also prepared and included in the biological evaluation. The inhibitory potency of the sodium-calcium exchanger was screened on both cell types by measuring their effect on 45Ca(2+) uptake. Among the most active compounds, N-(2-amino-5-chloro-4-nitrobenzoyl)-N'-(1-naphtylmethyl)guanidine (IC(50)=3.4 microM) was found more active than amiloride (IC(50)=690 microM) and 3,4-dichlorobenzamil (IC(50)=15.2 microM), the reference inhibitor. |
| Databáze: | OpenAIRE |
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