179678-91-2

Upstream product

• 179678-90-1 (S)-3-Isobutyl-4-(4-methoxy-benzyl)-1-methoxymethoxy-5-[1-(4-methoxy-phenyl)-meth-(Z)-ylidene]-piperazine-2,6-dione 
• 7517-19-3 methyl (L)-leucinate hydrochloride 
• 179678-66-1 N-(1-tert-butoxy-acet-2-yl)-(S)-leucine methyl ester 
• 179678-71-8 (S)-1-Hydroxy-3-isobutyl-4-(4-methoxy-benzyl)-piperazine-2,6-dione 
• 162715-72-2 N-p-methoxybenzyl-N-carboxymethyl-(S)-leucine methyl ester 
• 360556-27-0 (S)-2-[Hydroxycarbamoylmethyl-(4-methoxy-benzyl)-amino]-4-methyl-pentanoic acid methyl ester 
• 162715-73-3 1-methoxymethoxy-3S-isobutyl-4-p-methoxybenzylpiperazine-2,6-dione 
• 162715-71-1 N-p-methoxybenzyl-N-(1-tert-butoxy-acet-2-yl)-(S)-leucine methyl ester 
• 179678-70-7 (S)-2-[(2,5-Dioxo-pyrrolidin-1-yloxycarbonylmethyl)-(4-methoxy-benzyl)-amino]-4-methyl-pentanoic acid methyl ester 
• 360556-38-3 Methanesulfonic acid (R)-[(2S,6S)-6-isobutyl-1-(4-methoxy-benzyl)-4-methoxymethoxy-3,5-dioxo-piperazin-2-yl]-(4-methoxy-phenyl)-methyl ester 
• 179678-89-8 (3S,5S)-3-[(R)-Hydroxy-(4-methoxy-phenyl)-methyl]-5-isobutyl-4-(4-methoxy-benzyl)-1-methoxymethoxy-piperazine-2,6-dione 

Relevant academic research and scientific papers

Synthesis of natural flutimide and analogous fully substituted pyrazine-2,6-diones, endonuclease inhibitors of influenza virus

Flutimide, a fully substituted 1-hydroxy-3H-pyrazine-2,6-dione, is a fungal metabolite isolated from a new species of Delitschia cofertaspora. It has been shown to selectively inhibit cap-dependent endonuclease activity of influenza virus A. The inhibition of this activity is a target for the potential development of a therapeutic agent to treat influenza infections. A convergent total synthesis of flutimide starting from L-leucine has been described. The synthetic methodology has been extended to include the synthesis of specifically designed aromatic analogues of flutimide, some of which exhibited greater than 7-fold improvement in activity. The most potent compounds were those with p-fluorobenzylidene or p-methoxybenzylidene substitutions at C-5 of 3H-pyrazine-2,6-dione and showed IC50 values of 0.9 and 0.8 μM, respectively. The details of the rationale for the synthetic design, syntheses, and biological activities of these analogues are described.