Molecular pharmacology of the amiloride analog 3-amino-6-chloro-5-[(4-chloro-benzyl)amino]-N-[[(2,4-dimethylbenzyl)-amino]iminomethyl]-pyrazinecarboxamide (CB-DMB) as a pan inhibitor of the Na+-Ca2+ exchanger isoforms NCX1, NCX2, and NCX3 in stably transfected cells was written by Secondo, Agnese;Pannaccione, Anna;Molinaro, Pasquale;Ambrosino, Paolo;Lippiello, Pellegrino;Esposito, Alba;Cantile, Maria;Khatri, Priti R.;Melisi, Daniela;Di Renzo, Gianfranco;Annunziato, Lucio. And the article was included in Journal of Pharmacology and Experimental Therapeutics in 2009.Reference of 1458-01-1 This article mentions the following:
With the help of single-cell microfluorimetry, 45Ca2+ radiotracer fluxes, and patch-clamp in whole-cell configuration, the authors examined the effect of the amiloride derivative 3-amino-6-chloro-5-[(4-chloro-benzyl)amino]-N-[[(2,4-dimethylbenzyl) amino]-iminomethyl]-pyrazinecarboxamide (CB-DMB) on the activity of the three isoforms of the Na+/Ca2+ exchanger (NCX) and on several other membrane currents including voltage- and pH-sensitive ones. This amiloride analog suppressed the bidirectional activity of all NCX isoforms in a concentration-dependent manner. The IC50 values of CB-DMB were in the nanomolar range for the outward and the inward components of the bidirectional NCX1, NCX2, and NCX3 activity. Deletion mutagenesis showed that CB-DMB inhibited NCX activity mainly at level of the f-loop but not through the interaction with Gly 833 located at the level of the α2 repeat. CB-DMB suppressed in the micromolar range the other plasma membrane currents encoded by voltage-dependent Ca2+ channels, tetrodotoxin-sensitive Na+ channels, and pH-sensitive ASIC1a. Collectively, the data of the present study showed that CB-DMB, when used in the nanomolar range, is one of the most potent compounds that can block the activity of the three NCX isoforms when they work both in the forward and in the reverse modes of operation without interfering with other ionic channels. In the experiment, the researchers used many compounds, for example, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1Reference of 1458-01-1).
Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1) belongs to pyrazine derivatives. Pyrazine heterocycles and their benzo derivatives possess many interesting properties, including chemical reactivity profiles, and have diverse applications in total synthesis, medicine, chemical biology, materials, dyes, and imaging. Pyrazine heterocycles and their benzo derivatives possess many interesting properties, including chemical reactivity profiles, and have diverse applications in total synthesis, medicine, chemical biology, materials, dyes, and imaging.Reference of 1458-01-1