94944-70-4

Basic information

• Product Name: 1-[4-(1,2,3,4-TETRAHYDROXYBUTYL)-1H-IMIDAZOL-2-YL]ETHANONE
• Synonyms: 1-[4-(1,2,3,4-TETRAHYDROXYBUTYL)-1H-IMIDAZOL-2-YL]ETHANONE;2-acetyl-4(5)-tetrahydroxybutylimidazole;2-ACETYL-4(5)-(1,2,3,4-TETRAHYDROXYBUTYL)-IMIDAZOLE (THI);2-Athbi;Ethanone, 1-(4-(1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)-, (1R-(1R*,2S*,3R*))-;2-Acetyl-5-tetrahydroxybutyl Imidazole;Ethanone, 1-[5-[(1R,2S,3R)-1,2,3,4-tetrahydroxybutyl]-1H-iMidazol-2-yl]-;Ethanone, 1-[4-(1,2,3,4-tetrahydroxybutyl)-1H-iMidazol-2-yl]-, [1R-(1R*,2S*,3R*)]- (9CI)
• CAS NO: 94944-70-4
• Molecular Formula: C₉H₁₄N₂O₅
• Molecular Weight: 230.22
• Mol File: 94944-70-4.mol
• Article Data: 9

Chemical Properties

• Melting Point: approximate 230℃ (dec.)
• Boiling Point: 613.5°Cat760mmHg
• Flash Point: 324.8°C
• Appearance: white to light brown/Powder
• Density: 1.536g/cm³
• Vapor Pressure: 6.58E-16mmHg at 25°C
• Refractive Index: 1.635
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble2mg/mL, clear (warmed)
• PKA: 10.63±0.10(Predicted)
• Water Solubility: Soluble in distilled water, DMSO (>5 mg/ml), clear (warmed), and PBS pH 7.2 (~0.15 mg/ml).
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in distilled water may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: 1-[4-(1,2,3,4-TETRAHYDROXYBUTYL)-1H-IMIDAZOL-2-YL]ETHANONE(CAS DataBase Reference)
• NIST Chemistry Reference: 1-[4-(1,2,3,4-TETRAHYDROXYBUTYL)-1H-IMIDAZOL-2-YL]ETHANONE(94944-70-4)
• EPA Substance Registry System: 1-[4-(1,2,3,4-TETRAHYDROXYBUTYL)-1H-IMIDAZOL-2-YL]ETHANONE(94944-70-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• Hazardous Substances Data: 94944-70-4(Hazardous Substances Data)

Usage

Description

THI (94944-70-4) was identified as a biologically active impurity in caramel food coloring.1 It is a potent inhibitor of sphingosine-1-phosphate (S1P) lyase.2 It disrupts lymphocyte egress from lymphoid tissue by interfering with S1P gradients.3,4 The novel immunomodulatory activity of THI and its biochemical mechanism may represent a new target for the development of new generation of immunosuppressants.5

Uses

Different sources of media describe the Uses of 94944-70-4 differently. You can refer to the following data:
1. Sphingosine-1-phosphate (S1P) lyase catalyzes the irreversible decomposition of S1P to hexadecanaldehyde and phosphoethanolamine. 2-Acetyl-5-tetrahydroxybutyl imidazole (THI) is an inhibitor of S1P lyase. Because S1P lyase is primarily expressed in lymphatic tissue, treatment of mice with THI (50 μg/ml in drinking water) increases lymphoid tissue S1P concentrations 100-fold, reducing lymphocyte egress from thymus and peripheral lymphoid organs. The resulting lymphopenia is reversible following cessation of THI treatment. Reducing S1P lyase activity results in therapeutic levels of immunosuppression without the non-lymphoid lesions that result from synthetic S1P receptor agonists.
2. 2-Acetyl-4-(1,2,3,4-tetrahydroxybutyl)imidazole used for treatment of autoimmune disorders.

Biochem/physiol Actions

2-Acetyl-5-tetrahydroxybutyl imidazole (THI) can block S1P lyase in vivo and up-regulates circulatory and tissue S1P levels. It has the ability to repress dystrophic muscle degeneration.

References

1) MacKenzie et al. (1992), Toxicity Studies of Caramel Colour III and 2-Acetyl-4(5)-Tetrahydroxybutylimidazole in F344 rats; Food Chem. Toxicol. 30 417 2) Ohtoyo et al. (2015), Sphingosine 1-phosphate lyase inhibition by 2-acetyl-4-(tetrahydroxybutyl)imidazole (THI) under conditions of vitamin B6 deficiency; Mol.Cell Biochem. 400 125 3) Gugasyan et al. (1998), Emigration of mature T cells from the thymus is inhibited by the imidazole-based compound 2-acetyl-4-tetrahydroxybutylimidazole; Immunology 93 398 4) Schwab et al. (2005), Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients; Science 309 1735 5) Bradbury et al. (1997), The immunomodulatory compound 2-acetyl-4-tetrahydroxybutyl imidazole causes sequestration of lymphocytes in non-lymphoid tissue; Immunol. Cell Biol. 75 497

InChI:InChI=1/C9H14N2O5/c1-4(13)9-10-2-5(11-9)7(15)8(16)6(14)3-12/h2,6-8,12,14-16H,3H2,1H3,(H,10,11)/t6-,7-,8-/m1/s1

Upstream product

• 26419-66-9 2-methyl-1,3-dithiolane-2-carboxaldehyde 
• 643-71-0 D-glucosone 
• 1294498-22-8 C₆H₁₁NO₂ 
• 6333-49-9 1-amino-1-deoxy-D-arabino-hexulose acetate 
• 66-84-2 D-(+)-glucosamine hydrochloride 
• 1078691-95-8 (+)-D-glucosamine hydrochloride 
• 19479-65-3 2-ethoxyacrylonitrile 
• 1201794-87-7 1-amino-1-deoxy-D-fructose acetic acid salt 
• 185798-10-1 1-[4-((S)-2,2-Diethyl-[1,3]dioxolan-4-ylethynyl)-1-ethoxymethyl-1H-imidazol-2-yl]-ethanone 
• 185798-08-7 4-((S)-2,2-Diethyl-[1,3]dioxolan-4-ylethynyl)-1-ethoxymethyl-1H-imidazole 
• 185798-25-8 (1'R,2'S,3'R)-2-acetyl-4-<3',4'-O-(3'-pentylidene)-1',2',3',4'-tetrahydroxy-1'-butyl>-1-(ethoxymethyl)imidazole 
• 170882-83-4 (3'S)-(E)-2-acetyl-4-<3',4'-O-(3'-pentylidene)-3',4'-dihydroxybut-1'-enyl>-1-(ethoxymethyl)imidazole 
• 170882-82-3 (3'S)-(E)-4-<3',4'-O-(3'-pentylidene)-3',4'-dihydroxybut-1'-enyl>-1-(ethoxymethyl)imidazole 
• 67-56-1 methanol 

Downstream Products

• 1160957-37-8 (1R,2S,3R)-1-(2-(1-hydroxyethyl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol 
• 1160957-32-3 1-(1-methyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone 
• 1258455-16-1 C₉H₁₂⁽²⁾H₃N₃O₅ 
• 1223368-83-9 C₃₄H₃₇N₃O₅ 
• 1223368-84-0 C₁₅H₂₃N₃O₅ 
• 1054544-16-9 C₁₆H₂₁N₃O₅ 
• 1055027-48-9 (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol 
• 1258454-93-1 C₁₀H₁₅N₃O₅ 

Relevant articles and documents

Asymmetric synthesis of (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole

A method for preparing the biologically active compound (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole 1 using a palladium (0) catalysed coupling of 1-ethoxymethyl-4-iodomidazole 2 to the functionalised vinylstannane 3 and the Sharpless catalytic asymmetric dihydroxylation is reported.

A Convenient Synthesis of 2-Acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)imidazole

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Practical synthesis of potent sphingosine-1-phosphate lyase inhibitors THI and LX2931

A practical and scalable synthesis of in vivo sphingosine-1-phosphate lyase inhibitor LX2931 (1) is described. The synthetic route features an improved Büchi cyclocondensation of 2-ethoxyacrylonitrile (3) with either 1-amino-1-deoxy-d-fructose acetate (4a) or d-(+)-glucosamine hydrochloride (4b) to produce 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone (2, THI), followed by oximation of THI and acid-promoted oxime isomerization to give LX2931 (1).

Inhibition of sphingosine-1-phosphate lyase for the treatment of autoimmune disorders

During nearly a decade of research dedicated to the study of sphingosine signaling pathways, we identified sphingosine-1-phosphate lyase (S1PL) as a drug target for the treatment of autoimmune disorders. S1PL catalyzes the irreversible decomposition of sphingosine-1-phosphate (S1P) by a retro-aldol fragmentation that yields hexadecanaldehyde and phosphoethanolamine. Genetic models demonstrated that mice expressing reduced S1PL activity had decreased numbers of circulating lymphocytes due to altered lymphocyte trafficking, which prevented disease development in multiple models of autoimmune disease. Mechanistic studies of lymphoid tissue following oral administration of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI) 3 showed a clear relationship between reduced lyase activity, elevated S1P levels, and lower levels of circulating lymphocytes. Our internal medicinal chemistry efforts discovered potent analogues of 3 bearing heterocycles as chemical equivalents of the pendant carbonyl present in the parent structure. Reduction of S1PL activity by oral administration of these analogues recapitulated the phenotype of mice with genetically reduced S1PL expression.