Synthesis and preliminary evaluation of amiloride analogs as inhibitors of the urokinase-type plasminogen activator (uPA) was written by Matthews, Hayden;Ranson, Marie;Tyndall, Joel D. A.;Kelso, Michael J.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2011.Formula: C6H7ClN4O2 This article mentions the following:
A known side-activity of the oral potassium-sparing diuretic drug amiloride is inhibition of the enzyme urokinase-type plasminogen activator (uPA, K i = 7 μM), a promising anticancer target. Several studies have demonstrated significant antitumor/metastasis properties for amiloride in animal cancer models and it would appear that these arise, at least in part, through inhibition of uPA. Selective optimization of amiloride’s structure for more potent inhibition of uPA and loss of diuretic effects would thus appear as an attractive strategy towards novel anticancer agents. A preliminary structure-activity exploration of amiloride analogs as inhibitors of uPA is reported. A key finding was that the well-studied 5-substituted analogs ethylisopropyl amiloride (EIPA) and hexamethylene amiloride (HMA) are approx. twofold more potent than amiloride as uPA inhibitors. In the experiment, the researchers used many compounds, for example, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1Formula: C6H7ClN4O2).
Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1) belongs to pyrazine derivatives. Pyrazine is an N-heterocyclic moiety, and it can be easily prepared from ethylenediamine and 1,2-diketone, α-hydroxyketone, α-methyl ketone. Pyrazines undergo nearly all of the same reactions as pyrimidines, from nucleophilic substitution (SNAr) to palladium-catalyzed cross coupling reactions.Formula: C6H7ClN4O2