Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic-reperfusion injury.
A novel series of benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines were designed and synthesized as Na(+)/H(+)exchanger inhibitors. Most of them were found to inhibit NHE1-mediated platelet swelling in a concentration-dependent manner, and to have significant cardioprotective effect against myocardial ischemic-reperfusion injury, among which compounds 10a and 34 were more potent than cariporide in both in vivo and in vitro tests.
Zhang
Rui
R
Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
Lei
Lin
L
Xu
Yun-Gen
YG
Hua
Wei-Yi
WY
Gong
Guo-Qing
GQ
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy*; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry
D006146:Guanidines; D007093:Imidazoles; D017923:Sodium-Hydrogen Exchangers; C029899:imidazole