Abstract
The C-3 substituents effect on NHE-1 inhibitory activity of (5-arylfuran-2-ylcarbonyl)guanidines, previously identified as potent NHE-1 inhibitors, was investigated. The introduction of amine or alkyl groups at the 3-position of the furan ring, next to the acylguanidine moiety, remarkably improves NHE-1 inhibitory potency. Especially the important finding is that 5-(2,5-dichloro)phenyl and 5-(2-methoxy-5-chloro)phenyl derivatives exhibit high NHE-1 inhibitory activities (IC50 < 0.02 microM) that match those of 3-unsubstituted derivatives.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cardiotonic Agents / chemical synthesis
-
Guanidine / analogs & derivatives
-
Guanidine / chemical synthesis*
-
Guanidine / pharmacology*
-
Heart / drug effects
-
Heart / physiopathology
-
In Vitro Techniques
-
Inhibitory Concentration 50
-
Myocardial Ischemia / drug therapy
-
Myocardial Reperfusion Injury / drug therapy
-
Rats
-
Sodium-Hydrogen Exchangers / antagonists & inhibitors*
-
Structure-Activity Relationship
Substances
-
Cardiotonic Agents
-
Sodium-Hydrogen Exchangers
-
growth factor-activatable Na-H exchanger NHE-1
-
Guanidine