3-Substituted-(5-arylfuran-2-ylcarbonyl)guanidines as NHE-1 inhibitors.
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.
Lee
Sunkyung
S
Bio-organic Science Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, Republic of Korea.
Kim
Taemi
T
Lee
Byung Ho
BH
Yoo
Sung-eun
SE
Lee
Kyunghee
K
Yi
Kyu Yang
KY
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis; D019791:Guanidine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D017202:Myocardial Ischemia / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D051381:Rats; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D019791:Guanidine