Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic-reperfusion injury

Rui Zhang; Lin Lei; Yun-Gen Xu; Wei-Yi Hua; Guo-Qing Gong

doi:10.1016/j.bmcl.2007.02.035

Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic-reperfusion injury

Bioorg Med Chem Lett. 2007 May 1;17(9):2430-3. doi: 10.1016/j.bmcl.2007.02.035. Epub 2007 Feb 17.

Authors

Rui Zhang¹, Lin Lei, Yun-Gen Xu, Wei-Yi Hua, Guo-Qing Gong

Affiliation

¹ Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.

PMID: 17346962
DOI: 10.1016/j.bmcl.2007.02.035

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Platelets / drug effects
Chemistry, Pharmaceutical / methods
Drug Design
Drug Evaluation, Preclinical
Guanidines / chemistry
Guanidines / pharmacology*
Imidazoles / chemistry
Imidazoles / pharmacology*
Inhibitory Concentration 50
Models, Chemical
Molecular Conformation
Rats
Reperfusion Injury / drug therapy*
Sodium-Hydrogen Exchangers / chemistry

Substances

Guanidines
Imidazoles
Sodium-Hydrogen Exchangers
imidazole