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 (IC50 = 79 nM for the rat enzyme) and a derivative of 5-flurouracil . It reduces acid ceramidase activity in a dose- and time-dependent manner and induces intracellular accumulation of various ceramide species, including C18 ceramide , C16 ceramide , and C14 ceramide in SW403 colon and LNCaP prostate cancer cells. Carmofur induces apoptosis in SW403 cells without inhibiting DNA synthesis (IC50 = 1,212 mM for human thymidylate synthetase). It also reduces acid ceramidase activity and increases ceramide accumulation in mouse lung and brain when administered at doses of 10 and 30 mg/kg.

Originator

Mifurol,Mitsui,Japan,1981

Uses

Different sources of media describe the Uses of 61422-45-5 differently. You can refer to the following data:
1. antineoplastic
2. Carmofur has been used as an inhibitor of acid ceramidase to study its effects on glucosylsphingosine (GlcSph) production in human embryonic kidney 293T (HEK293T) cells. It has also been used as an inhibitor of acid ceramidase to study its effects on acid‐mediated hydrolysis of ceramide which kicks-in consumption and the generation of sphingosine .

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

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

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

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