Synthesis of Novel Ligustrazine Derivatives as Na+/H+Exchange Inhibitors
- 12 November 2010
- journal article
- research article
- Published by Wiley in Chemistry & Biodiversity
- Vol. 7 (11) , 2727-2736
Abstract
A novel series of 3,5,6-trimethylpyrazine-2-methoxy (or methylamino) substituted benzoyl-guanidine derivatives were designed and synthesized as Na+/H+ exchange (NHE) inhibitors. In this study, compounds with electron-withdrawing substituents on the benzene ring seemed to improve NHE-1 inhibitory activities. Compounds 6d, 6k, and 6l were found to be potent inhibitors of NHE-1 (IC50=3.0±1.6, 3.0±1.4, and 1.6±0.4 nmol/l, resp.). Furthermore, they showed a remarkable reduction of infarct size in the rat myocardial infarction model in vivo.Keywords
This publication has 20 references indexed in Scilit:
- Synthesis and Na+/H+ Exchanger‐1 Inhibitory Activity of Substituted (Quinolinecarbonyl)guanidine DerivativesChemistry & Biodiversity, 2009
- Design, synthesis and biological evaluation of novel substituted benzoylguanidine derivatives as potent Na+/H+ exchanger inhibitorsBioorganic & Medicinal Chemistry Letters, 2009
- Natural products to drugs: natural product-derived compounds in clinical trialsNatural Product Reports, 2008
- Benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ischemic-reperfusion injuryBioorganic & Medicinal Chemistry Letters, 2007
- (5-Arylfuran-2-ylcarbonyl)guanidines as Cardioprotectives through the Inhibition of Na+/H+ Exchanger Isoform-1Journal of Medicinal Chemistry, 2005
- The Na+/H+ exchanger isoform 1The International Journal of Biochemistry & Cell Biology, 2005
- Recent advances in the structural modification of ligustrazine: Cerebro- and cardiovascular activity of ligustrazine derivativesDrugs of the Future, 2005
- An overview of inhibitors of Na+/H+ exchangerEuropean Journal of Medicinal Chemistry, 2003
- Synthesis and biological evaluation of aroylguanidines related to amiloride as inhibitors of the human platelet Na+/H+ exchangerBioorganic & Medicinal Chemistry, 2002
- Regulation of the Na+/H+Exchanger in the Mammalian MyocardiumJournal of Molecular and Cellular Cardiology, 1997