59157-06-1

Basic information

• Product Name: 5,10-Dioxo-5H,10H-diimidazo(1,5-a:1,5-d)pyrazine-1,6-dicarbonyl dichloride
• Synonyms: 5,10-dioxo-5H,10H-diimidazo[1,5-a:1',5'-d]pyrazine-1,6-dicarboxylic acid dichloride;4H,9H-diimidazopyrazin 1,6-dicarbonyldichlorid;5,10-dioxo-5H,10H-diimidazo[1,5-a,1',5'-d]pyrazinedicarbonyl-1,6-dichloride;5,10-dioxo-5H,10H-diimidazo[1,5-a:1',5'-d]pyrazine-1,6-dicarbonyl dichloride;
• CAS NO: 59157-06-1
• Molecular Formula: C₁₀H₂Cl₂N₄O₄
• Molecular Weight: 313.056
• Mol File: 59157-06-1.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 729.7°Cat760mmHg
• Flash Point: 395.1°C
• Density: 2.13g/cm³
• CAS DataBase Reference: 5,10-Dioxo-5H,10H-diimidazo(1,5-a:1,5-d)pyrazine-1,6-dicarbonyl dichloride(CAS DataBase Reference)
• NIST Chemistry Reference: 5,10-Dioxo-5H,10H-diimidazo(1,5-a:1,5-d)pyrazine-1,6-dicarbonyl dichloride(59157-06-1)
• EPA Substance Registry System: 5,10-Dioxo-5H,10H-diimidazo(1,5-a:1,5-d)pyrazine-1,6-dicarbonyl dichloride(59157-06-1)

Safety Data

• Hazardous Substances Data: 59157-06-1(Hazardous Substances Data)

Upstream product

• 570-22-9 4,5-imidazoledicarboxylic acid 

Downstream Products

• 89562-34-5 5,10-dioxo-N¹,N⁶-diphenyl-5,10-dihydrodiimidazo[1,5-a:1',5'-d]pyrazine-1,6-dicarboxamide 
• 62255-05-4 1H-imidazole-4,5-dicarboxylic acid bis-benzylamide 
• 62254-97-1 1H-imidazole-4,5-dicarboxylic acid bis-butylamide 
• 474013-77-9 5,10-dioxo-5H,10H-diimidazolo[1,5-a:1',5'-d]pyrazine-1,6-dicarboxylic acid diphenyl ester 
• 627874-38-8 2-{[6-(1-benzyloxycarbonyl-3-methyl-butylcarbamoyl)-5,10-dioxo-5H,10H-diimidazo[1,5-a;1',5'-d]pyrazine-1-carbonyl]-amino}-4-methyl-pentanoic acid benzyl ester 
• 233584-99-1 4,5-bis{[(1,1-dimethylethoxy)-(S)-phenylalanyl]carbonyl}-1H-imidazole 
• 627874-20-8 2-{[6-(1-tert-butoxycarbonyl-2-phenyl-ethylcarbamoyl)-5,10-dioxo-5H,10H-diimidazo[1,5-a;1',5'-d]pyrazine-1-carbonyl]-amino}-3-phenyl-propionic acid tert-butyl ester 
• 476478-16-7 2-{[6-(1-benzyloxycarbonyl-2-methyl-propylcarbamoyl)-5,10-dioxo-5H,10H-diimidazo[1,5-a;1',5'-d]pyrazine-1-carbonyl]-amino}-3-methyl-butyric acid benzyl ester 
• 867061-98-1 N,N'-di-3,4-dichlorophenyl-5,10-dioxo-5H,10H-diimidazo[1,5-a:1',5'-d]pyrazine-1,6-dicarboxamide 
• 1018894-81-9 C₂₆H₂₂N₆O₄ 
• 1162645-88-6 C₂₈H₂₂N₆O₈ 
• 1162645-90-0 C₃₀H₂₆N₆O₈ 
• 1162645-94-4 C₄₂H₃₄N₆O₈ 
• 1217317-84-4 C₆₂H₇₂N₁₂O₁₄S₂ 

Relevant articles and documents

An inhibitor of fatty acid synthase thioesterase domain with improved cytotoxicity against breast cancer cells and stability in plasma

It is well recognized that many cancers are addicted to a constant supply of fatty acids (FAs) and exhibit brisk de novo FA synthesis. Upregulation of a key lipogenic enzyme, fatty acid synthase (FASN), is a near-universal feature of human cancers and their precursor lesions, and has been associated with chemoresistance, tumor metastasis, and diminished patient survival. FASN inhibition has been shown to be effective in killing cancer cells, but progress in the field has been hindered by off-target effects and poor pharmaceutical properties of candidate compounds. Our initial hit (compound 1) was identified from a high-throughput screening effort by the Sanford-Burnham Center for Chemical Genomics using purified FASN thioesterase (FASN-TE) domain. Despite being a potent inhibitor of purified FASN-TE, compound 1 proved highly unstable in mouse plasma and only weakly cytotoxic to breast cancer (BC) cells in vitro. An iterative process of synthesis, cytotoxicity testing, and plasma stability assessment was used to identify a new lead (compound 41). This lead is more cytotoxic against multiple BC cell lines than tetrahydro-4-methylene-2S-octyl-5-oxo-3R-furancarboxylic acid (the literature standard for inhibiting FASN), is stable in mouse plasma, and shows negligible cytotoxic effects against nontumorigenic mammary epithelial cells. Compound 41 also has drug-like physical properties based on Lipinski’s rules and is, therefore, a valuable new lead for targeting fatty acid synthesis to exploit the requirement of tumor cells for fatty acids.

AMIDO-SUBSTITUTED AZOLE COMPOUNDS

The present invention relates to compounds of general formula (I), in which X1, X2, R1, R2, R4, R5, R7, and R8 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.

AMIDO-SUBSTITUTED AZOLE COMPOUNDS

The present invention relates to amido-substituted azole compounds of general formula (I), in which X1, X2, R1, R2, R4, R5, R7 and R8 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.