4-Substituted (benzo[b]thiophene-2-carbonyl)guanidines as novel Na+/H+ exchanger isoform-1 (NHE-1) inhibitors.
A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficacy. Especially the 4-nitro 20 and cyano 50 compounds excellently improved the cardiac function and reduced infarct size against ischemia/reperfusion injury.
Lee
Sunkyung
S
Medicinal Science Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, Republic of Korea.
Lee
Hyunsuk
H
Yi
Kyu Yang
KY
Lee
Byung Ho
BH
Yoo
Sung-Eun
SE
Lee
Kyunghee
K
Cho
Nam Sook
NS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D009203:Myocardial Infarction / Q000188:drug therapy; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors; D051381:Rats; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D020033:Protein Isoforms; D017923:Sodium-Hydrogen Exchangers