5-Amino-1-β-D-ribofuranosyl-1H-imidazol-4-carboxamid

Bezeichnung:5-Amino-1-β-D-ribofuranosyl-1H-imidazol-4-carboxamid

CAS-Nr2627-69-2

Englisch Name:AICAR

CBNumberCB1675294

SummenformelC9H14N4O5

Molgewicht258.23

MOL-Datei2627-69-2.mol

Synonyma

5-Amino-1-β-D-ribofuranosyl-1H-imidazol-4-carboxamid

5-Amino-1-β-D-ribofuranosyl-1H-imidazol-4-carboxamid physikalisch-chemischer Eigenschaften

Schmelzpunkt	214-215 °C
Siedepunkt	726.3±60.0 °C(Predicted)
Dichte	2.06±0.1 g/cm3(Predicted)
storage temp.	-20°C
Löslichkeit	H₂O: >10 mg/mL
Aggregatzustand	powder
pka	13.27±0.70(Predicted)
Farbe	tan
Wasserlöslichkeit	Soluble in DMSO at 2mg/ml. Soluble in water or ethanol at less than 1mg/ml
maximale Wellenlänge (λmax)	265nm(NaOH)(lit.)
Merck	14,16
Stabilität	Stable for 2 years from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20°C for up to 3 months.
InChIKey	RTRQQBHATOEIAF-UUOKFMHZSA-N
CAS Datenbank	2627-69-2(CAS DataBase Reference)
EPA chemische Informationen	1H-Imidazole-4-carboxamide, 5-amino-1-.beta.-D-ribofuranosyl- (2627-69-2)

Sicherheit

Kennzeichnung gefährlicher	Xi,T
R-Sätze:	36/37/38-61
S-Sätze:	26-36-45-53
WGK Germany	3
TSCA	Yes
HS Code	29349990

Gefahreninformationscode (GHS)

AICAR Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
AICAR (2627-69-2) activates AMP-activated protein kinase (AMPK). Promotes ligand-independent activation of the insulin receptor.1 Promotes skeletal muscle autophagy via activation of FoxO3a.2 Controls smooth muscle cell hyperproliferation in vascular disease.3 ?Induces osteogenic differentiation in mesenchymal stem cells.4 Inhibits proinflammatory response in glial cells.5 Cell permeable.
Chemische Eigenschaften
Solid
Originator
AICA,BIOMOL
Verwenden
glucose uptake stimulant; AMPK activator
Verwenden
5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside is used as a cell permeable activator of AMP-activated protein kinase (AMPK), a metabolic master regulator that is activated in times of reduced energy availability (high cellular AMP:ATP ratios) and serves to inhibit anabolic processes. In vivo, pharmacologic activation of AMPK with AICAR mimics exercise and triggers insulin-independent glucose uptake by skeletal muscle.
Verwenden
AICAR is a nucleoside analogue that is able to enter nucleoside pools and is able to significantly increase levels of adenosine during periods of ATP breakdown. Adenosine-regulating agents (ARAs) hav e been recognized for therapeutic potential in myocardial ischemia. Cardioprotective.
Definition
ChEBI: A 1-ribosylimidazolecarboxamide in which the carboxamide group is situated at position 4 of the imidazole ring, which is further substituted at position 5 by an amino group. A purine nucleoside analogue and activator of AMP-activated protein kinase, it is is used for the treatment of acute lymphoblastic leukemia and is reported to have cardioprotective effects.
Manufacturing Process
Adenosine 3', 5'-cyclic phosphate N'-oxide (76.0 g, 0.200 mole) as the dihydrate was dissolved in a solution of 400 ml DMSO and 31.0 g (0.204 mole) 1,5-diazabicyclo[5.4.0]undec-5-ene. The solution was cooled to 15°C and 40 ml methyl iodide was added with stirring at room temperature. After 30 min, the mixture had gelled; 1.5 L ethanol was added and the solid was thoroughly homogenized by vigorous stirring. The solid was filtered, and the resulting paste was resuspended in 2 L ethanol and homogenized. The product was again filtered, washed with ethanol and ether, and dried, giving 80.4 g of 1-methoxyadenosine 3',5'-cyclic phosphate suitable for further transformation (recrystallization from aqueous methanol with ether).
A solution of 30.0 g 1-methoxyadenosine 3',5'-cyclic phosphate (81.5 mmole), 20.0 g NaHCO3 (238 mmole), and 300 ml H2O was refluxed 45 mm. The pH of the solution was adjusted to 2.5 with Dowex 50x8 (H)+ while warm, and a water pump vacuum was applied to mixture to remove CO2. The pH was readjusted to 9-10 with NaOH, and the resin was removed by filtration. The solution was passed onto a column containing 400 ml Dowex 1x2 (formate, 100-200 mesh), and the column was washed well with water. The column was eluted with a gradient of 4 L water in the mixing chamber and 4 L 4 N formic acid in the reservoir. The first major product, coming after about 2 L eluate, was 5-amino-N-methoxy-1-β-D-ribofuranosylimidazole-4-carboxamidine 3',5'- cyclic phosphate, giving 5.4 g (19%) after evaporation of the solvent and trituration of the residue with ethanol (recrystallization from water). A solution of 5.0 g (14.3 mmoles) 5-amino-N-methoxy-1-β-Dribofuranosylimidazole- 4-carboxamidine 3',5'-cyclic phosphate in 200 ml H2 preheated to 60°C and containing approximately 5.0 g moist sponge nickel catalyst, was shaken with 2-3 atm. H2 at 60°C for 2 h. The filtered solution was evaporated to dryness to give 3.75 g of 5-amino-1-β-Dribofuranosylimidazole- 4-carboxamidine 3',5'-cyclic phosphate (82%), (recrystallization from water).
A mixture of 4.0 g (12.5 mmole) 5-amino-1-β-D-ribofuranosylimidazole-4- carboxamidine 3',5'-cyclic phosphate and 100 ml conc. NH4OH was heated in a bomb at 100°C for 16 h, then cooled and evaporated in vacuum. The residue was taken up in 100 ml H2O and applied to a 2.5x20 cm column of Dowex 1x2 (formate form, 100-200 mesh). After washing well with H2O the column was eluted with a gradient of 1 L H2O in the mixing chamber and 1 L 3 N formic acid in the reservoir. Fractions containing the product, appearing near the end of the elution, were evaporated. Trituration of the residue with EtOH gave 2.90 g (68%) of 5-amino-1-β-D-ribofuranosylimidazole-4- carboxamide 3',5'-cyclic phosphate.
The 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide may be produced by hydrolysis of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide 3',5'- cyclic phosphate with NaOH.
Therapeutic Function
Cardiotonic, Platelet aggregation inhibitor
Biologische Funktion
The first direct AMPK activator, 5-aminoimidazole-4-carboxamide riboside (AICAR), is an adenosine analog taken up into cells by adenosine transporters and phosphorylated by adenosine kinase, thus generating the AMP-mimetic, AICAR monophosphate (ZMP). Similarly to cellular AMP, ZMP binds to site 3 on the AMPKγ subunit. Although ZMP is a much less potent AMPK activator than AMP in cell-free systems, AICAR directly activates AMPK in most cells because ZMP can accumulate to millimolar concentrations in cells. AICAR is able to activate many other AMP-dependent enzymes, such as fructose-1,6-bisphosphatase.
Allgemeine Beschreibung
Adenosine monophosphate?protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide?ribonucleotide?(AICAR)?modulates cellular energy. It regulates lipid and glucose metabolism, pro-inflammatory responses,?cytokine production,?cell proliferation and apoptosis. AICAR improves ischemia or reperfusion injury and kidney fibrosis in rats. It provides protection against acute tubular necrosis.
Biologische Aktivität
Cell-permeable, allosteric activator of AMP-activated protein kinase (AMPK). Augments proliferation, differentiation and mineralization of osteoblastic MC3T3-EI cells and attenuates psychosine-induced expression of proinflammatory cytokines and iNOS in astrocytes.
Biochem/physiol Actions
AICAR is a cell permeable activator of AMP-activated protein kinase (AMPK), a metabolic master regulator that is activated in times of reduced energy availability (high cellular AMP:ATP ratios) and serves to inhibit anabolic processes. In vivo, pharmacologic activation of AMPK with AICAR mimics exercise and triggers insulin-independent glucose uptake by skeletal muscle.
Nebenwirkungen
AICAR is an AMPK (adenosine 5′-monophosphate (AMP)-activated protein kinase) activator that has been shown to have significant endurance-enhancing effects and is banned for use as a doping agent by the World Anti-Doping Agency. Overactivation of AMPK, or activation in the wrong tissues, can lead to serious side effects, including neurodegeneration or preventing cell division. Accumulation of naturally occurring AICAR in the body has also been linked to metabolic disorders in humans. However, AICAR has not been approved for human treatment and cannot be used as a drug. Therefore, its safety has yet to be verified.
Lager
-20°C
Clinical claims and research
AICAR has proved in vivo anti-tumor effects in xenograft models. It is currently under clinical trial phase I/II to treat patients with chronic lymphocytic leukemia and has shown good safety and tolerability properties, although some side effects have been reported.
Einzelnachweise
1) Chopra et al. (2012), Phosphorylation of the insulin receptor by AMP-activated protein kinase (AMPK) promotes ligand-independent activation of the insulin signalling pathway in rodent muscle; Diabetologia, 55 783 2) Sanchez et al. (2012), AMPK promotes skeletal muscle autophagy through activation of forkhead FoxO3a and interaction with Ulk1; J. Cell Biochem., 113 695 3) Ferri et al. (2012), AMP-activated protein kinase and the control of smooth muscle cell hyperproliferation in vascular disease; Vascul. Pharmacol., 56 9 4) Wu et al. (2011) AICAR, a small chemical molecule, primes osteogenic differentiation of adult mesenchymal stem cells; Int. J. Artif. Organs, 34 1128 5) Giri et al. (2004) 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside inhibits proinflammatory response in glial cells: a possible role of AMP-activated protein kinase; J. Neurosci., 24 479

AICAR Upstream-Materialien And Downstream Produkte

5-Amino-1-β-D-ribofuranosyl-1H-imidazol-4-carboxamid Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

2627-69-2, AICAR Verwandte Suche:

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