Abstract:
: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.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Rogister F,Laeckmann D,Plasman P,Van Eylen F,Ghyoot M,Maggetto C,Liégeois J,Géczy J,Herchuelz A,Delarge J,Masereel Bdoi
10.1016/s0223-5234(01)01247-8subject
Has Abstractpub_date
2001-07-01 00:00:00pages
597-614issue
7-8eissn
0223-5234issn
1768-3254pii
S0223523401012478journal_volume
36pub_type
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