(2-Aryl-5-methylimidazol-4-ylcarbonyl)guanidines and (2-aryl-5-methyloxazol-4-ylcarbonyl)guanidines as NHE-1 inhibitors.
A series of (2-aryl-5-methylimidazol-4-ylcarbonyl)guanidines and (2-aryl-5-methyloxazol-4-ylcarbonyl)guanidines were synthesized and evaluated as NHE-1 inhibitors. The structure-activity relationships well matched those of furan derivatives, which were previously investigated. The (2,5-disubstituted)phenyl compounds showed better activities than the other analogues in both imidazole and oxazole compounds. Especially, 2-(2,5-dichlorophenyl)imidazole 52, and 2-(2-methoxy-5-chlorophenyl)imidazole 54 compounds exhibited potent cardioprotective efficacy both in vitro and in vivo as well as high NHE-1 inhibitory activities.
Lee
Sunkyung
S
Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon 305-600, Republic of Korea.
Yi
Kyu Yang
KY
Youn
Sung Jun
SJ
Lee
Byung Ho
BH
Yoo
Sung-Eun
SE
D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors*; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D002316:Cardiotonic Agents; D027682:Cation Transport Proteins; D006146:Guanidines; D007093:Imidazoles; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers