61422-45-5

Basic information

• Product Name: Carmofur
• Synonyms: 2,4-dioxo-5-fluoro-n-hexyl-1,2,3,4-tetrahydro-1-pyrimidinecarboxamide;2,4-dioxo-5-fluoro-n-hexyl-3,4-dihydro-1(2h)-pyrimidinecarboxamidme;3,4-dihydro-2,4-dioxo-5-fluoro-n-hexyl-1(2h)-pyrimidinecarboxamid;hcfu;CARMOFUR;HCFUTM;1-(N-HEXYLCARBAMOYL)-5-FLUOROURACIL;5-FLUORO-1-HEXYLCARBAMOYLURACIL
• CAS NO: 61422-45-5
• Molecular Formula: C₁₁H₁₆FN₃O₃
• Molecular Weight: 257.26
• EINECS: 1312995-182-4
• Product Categories: Pharmaceutical material and intermeidates
• Mol File: 61422-45-5.mol
• Article Data: 5

Chemical Properties

• Melting Point: 110-111
• Appearance: white to off-white/
• Density: 1.2287 (estimate)
• Refractive Index: 1.525
• Storage Temp.: 2-8°C
• Solubility: DMSO: >15mg/mL
• PKA: 6.94±0.10(Predicted)
• Merck: 14,1844
• CAS DataBase Reference: Carmofur(CAS DataBase Reference)
• NIST Chemistry Reference: Carmofur(61422-45-5)
• EPA Substance Registry System: Carmofur(61422-45-5)

Safety Data

• Hazard Codes: Xi,T
• Statements: 60-61-25
• Safety Statements: 45
• RIDADR: UN 2811 6.1 / PGII
• WGK Germany: 3
• RTECS: UV7714000
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 61422-45-5(Hazardous Substances Data)

Usage

Description

Carmofur is an inhibitor of acid ceramidase and a derivative of 5-flurouracil, which reduces acid ceramidase activity and induces intracellular accumulation of various ceramide species in cancer cells. It induces apoptosis in SW403 colon cancer cells without inhibiting DNA synthesis and has been used to study its effects on glucosylsphingosine production and acid-mediated hydrolysis of ceramide.

Uses

Used in Antineoplastic Applications:
Carmofur is used as an antineoplastic agent for its ability to reduce acid ceramidase activity and induce apoptosis in cancer cells, particularly in SW403 colon cancer cells.
Used in Research Applications:
Carmofur is used as an inhibitor of acid ceramidase in research settings to study its effects on glucosylsphingosine production in human embryonic kidney 293T (HEK293T) cells and its role in acid-mediated hydrolysis of ceramide, which contributes to consumption and the generation of sphingosine.

Originator

Mifurol,Mitsui,Japan,1981

Manufacturing Process

13.0 g (0.10 mol) of 5-fluorouracil was suspended in 60 ml of dimethyl acetamide, then 14.0 g (0.11 mol) of n-hexyl isocyanate was added thereto at room temperature and stirred at 50°C for 8 hours. After the reaction mixture was concentrated under reduced pressure, the residue was poured into 400 ml of water and resultant precipitate was filtered off. The precipitate was washed and dried and 19.3 g (75.0% yield) of 5-fluoro-1-(n-hexylcarbamoyl)uracil was obtained. The product was recrystallized from ether and there were obtained white crystals melting at 283°C (decomposition).

Therapeutic Function

Antineoplastic

Biochem/physiol Actions

Carmofur is a derivative of fluorouracil, an antimetabolite used as an antineoplastic agent.

InChI:InChI=1/C11H16FN3O3/c1-2-3-4-5-6-13-10(17)15-7-8(12)9(16)14-11(15)18/h7H,2-6H2,1H3,(H,13,17)(H,14,16,18)

Upstream product

• 51-21-8 5-fluorouracil 
• 2525-62-4 Hexyl isocyanate 

Downstream Products

• 1431627-99-4 3-benzoyl-5-fluoro-N-hexyl-2,4-dioxo-pyrimidine-1-carboxamide 
• 1431627-97-2 methyl 5-fluoro-3-(hexylcarbamoyl)-2,6-dioxo-pyrimidine-1-carboxylate 
• 1431627-96-1 5-fluoro-N-hexyl-3-(2-methylpropanoyl)-2,4-dioxo-pyrimidine-1-carboxamide 
• 51-21-8 5-fluorouracil 

Relevant articles and documents

Design and synthesis of uracil urea derivatives as potent and selective fatty acid amide hydrolase inhibitors

Fatty acid amide hydrolase (FAAH) is one of the key enzymes involved in the biological degradation of endocannabinoids, especially anandamide. Pharmacological blockage of FAAH restores the levels of endocannabinoids, providing therapeutic benefits in the management of inflammation, depression and multiple sclerosis. In this study, a series of uracil urea derivatives as FAAH inhibitors were designed and synthesized. Structural modifications at the C5 position and side chain of N-hexyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide (1a) led to FAAH inhibitors with improved potency and selectivity. Structure-activity relationship (SAR) studies indicated that C5 electron-withdrawing substituents were preferred for optimal potency but not for selectivity, whereas replacement of the alkyl chain with phenylalkyl moieties or biphenyl groups significantly improved both inhibitory potency and selectivity towards FAAH. Two highly potent picomolar FAAH inhibitors (4c, IC50 = 0.3 ± 0.05 nM; 4d, IC50 = 0.8 ± 0.1 nM) were developed. Compound 4c inhibited FAAH in a rapid, selective, noncompetitive, and irreversible pattern. This study provides several highly potent and selective FAAH inhibitors and an optimized chemical scaffold for the development of FAAH inhibitors. We anticipate that these FAAH inhibitors will enable new possibilities in understanding FAAH functions and development of therapeutics for pain and inflammatory diseases.

Carbamyl uracil derivative and application thereof

The invention discloses a carbamyl uracil derivative and application thereof. The structural formula of the derivative is as shown in the description. The derivative is a novel compound with the endogenous cannabinoid hydrolase inhibiting function, and a new method is provided for inflammation and pain treatment.

5-Fluorouracil derivatives. I. The synthesis of 1-carbamoyl-5-fluorouracils

-