28822-58-4

Basic information

• Product Name: 3-ISOBUTYL-1-METHYLXANTHINE
• Synonyms: 1H-Purine-2,6-dione, 3,7-dihydro-1-methyl-3-(2-methylpropyl)-;3,7-dihydro-1-methyl-3-(2-methylpropyl)-1h-purine-6-dione;3-Isobutyl-1-methyl-3,7-dihydro-1H-purine-2,6-dione;3-Isobutyl-1-methylanxthine;3-isobutyl-1-methyl-xanthin;IMX;Isobutylmethylxanthine;Methylisobutylxanthine
• CAS NO: 28822-58-4
• Molecular Formula: C₁₀H₁₄N₄O₂
• Molecular Weight: 222.24
• EINECS: 249-259-3
• Product Categories: All Inhibitors;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 28822-58-4.mol
• Article Data: 4

Chemical Properties

• Melting Point: 200-201 °C(lit.)
• Boiling Point: 363.42°C (rough estimate)
• Flash Point: 223.3 °C
• Appearance: off-white/powder
• Density: 1.2042 (rough estimate)
• Vapor Pressure: 3.89E-08mmHg at 25°C
• Refractive Index: 1.6500 (estimate)
• Storage Temp.: −20°C
• Solubility: DMSO: 1 M with gentle warming
• PKA: 8.61±0.70(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
• BRN: 247859
• CAS DataBase Reference: 3-ISOBUTYL-1-METHYLXANTHINE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-ISOBUTYL-1-METHYLXANTHINE(28822-58-4)
• EPA Substance Registry System: 3-ISOBUTYL-1-METHYLXANTHINE(28822-58-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 24/25
• WGK Germany: 3
• RTECS: ZD8500000
• Hazardous Substances Data: 28822-58-4(Hazardous Substances Data)

Usage

Description

IBMX (28822-58-4) is a pan-specific inhibitor of phosphodiesterases (IC50=2-50 μM). Inhibition of PDEs leads to increased concentration of intracellular cAMP which activates PKA.2?IBMX does not inhibit PDE8 or PDE9.3?Weak adenosine receptor antagonist.4

Chemical Properties

White Needles with Yellow Cast

Uses

Different sources of media describe the Uses of 28822-58-4 differently. You can refer to the following data:
1. A nonspecific inhibitor of phosphodiesterases
2. phosphodiesterase inhibitor
3. 3-Isobutyl-1-methylxanthine is used in inhibition of phenylephrine-induced release of 5-hydroxytryptamine from neuroendocrine epithelial cells of the airway mucosa (IC50 = 1.3 uM). Also inhibits ion channels in the neuromuscular junction, GH3 cells, and vascular smooth muscle cells. Inhibits the growth of carcinoma cells both in vivo and in vitro in mice.

General Description

3-isobutyl-1-methylxanthine/IBMX is a non-selective, non-specific inhibitor of cAMP and cGMP phosphodiesterases. IBMX can induce melanogenesis, and can be used as a positive control in melanogenesis research. In oocyte research, IBMX assists in maintaining the germinal vesicle (GV) arrest of prophase I oocytes.

Biological Activity

Phosphodiesterase inhibitor (IC 50 values are 13, 18, 19, 32 and 50 μ M for PDE4, PDE3, PDE1, PDE5 and PDE2 respectively). Suppresses α -adrenoceptor-mediated 5-HT release from neuroendocrine epithelial cells (IC 50 = 1.3 μ M).

Biochem/physiol Actions

The increase in cAMP level as a result of phosphodiesterase inhibition by IBMX activates PKA, leading to decreased proliferation, increased differentiation, and induction of apoptosis. IBMX inhibits phenylephrine-induced release of 5-hydroxytryptamine from neuroendocrine epithelial cells of the airway mucosa (IC50: 1.3 μM). IBMX also serves as an adenosine receptor antagonist. IBMX has been shown to inhibit ion channels in the neuromuscular junction, GH3 cells, and vascular smooth muscle cells. IBMX induces calcium release from intracellular stores in sensory neurons.

Purification Methods

Recrystallise it from aqueous EtOH. [Beilstein 26

References

1) Beavo et al. (1970), Effects of xanthine derivatives on lipolysis and on adenosine 3′,5′-monophosphate phosphodiesterase activity; Mol. Pharmacol., 6 597 2) Tomes et al. (1993), Isobutylmethylxanthine and other classical cyclic nucleotide phosphodiesterase inhibitors affect cAMP-dependent protein kinase activity; Cell Signal., 5 615 3) Soderling et al. (2000), Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions; Curr. Opin. Cell Biol., 12 174 4) Daly et al. (1987), Adenosine receptors: development of selective agonists and antagonists; Prog. Clin. Biol. Res., 230 41

InChI:InChI=1/C10H14N4O2/c1-6(2)4-14-8-7(11-5-12-8)9(15)13(3)10(14)16/h5-6H,4H2,1-3H3,(H,11,12)

Synthetic route

7-Pivalyloxymethyl-1-methyl-3-isobutylxanthine (73018-01-6) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
hydrolysis;	76%

formic acid (64-18-6) + 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione (78033-18-8) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
With sodium hydroxide 1.) reflux, 2 h, 2.) reflux, 45 min; Multistep reaction;

7-Benzyl-3-isobutyl-1-methylxanthine (58481-23-5) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
With palladium dihydroxide In methanol

7-benzyl-1-methyl-3,7-dihydro-purine-2,6-dione (70404-25-0) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: K2CO3 / dimethylformamide 2: HCONH4; Pd(OH)2 / methanol View Scheme

1-methylxanthine (6136-37-4) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 41 percent / Na2CO3 / dimethylformamide / 17 h 2: 91 percent 3: 76 percent / hydrolysis View Scheme

1-methyl-7-<(pivaloyloxy)methyl>xanthine (69150-36-3) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent 2: 76 percent / hydrolysis View Scheme

6-amino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione (58481-39-3) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaNO2, AcOH / H2O / 2 h / Ambient temperature 2: Na2S2O4, 25percent aq. NH4OH / 20 - 50 °C 3: 2.) 2.2 M aq. NaOH / 1.) reflux, 2 h, 2.) reflux, 45 min View Scheme

1-isobutyl-3-methyl-urea (38014-54-9) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) acetic anhydride, 2.) 10percent aq. NaOH / 1.) 70 deg C, 2 h, 2.) from 20 to 70 deg C, 1 h 2: NaNO2, AcOH / H2O / 2 h / Ambient temperature 3: Na2S2O4, 25percent aq. NH4OH / 20 - 50 °C 4: 2.) 2.2 M aq. NaOH / 1.) reflux, 2 h, 2.) reflux, 45 min View Scheme

1-isobutyl-3-methyl-5-nitroso-6-amino uracil (54052-67-4) → 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: Na2S2O4, 25percent aq. NH4OH / 20 - 50 °C 2: 2.) 2.2 M aq. NaOH / 1.) reflux, 2 h, 2.) reflux, 45 min View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + methyl iodide (74-88-4) → 3-isobutyl-Paraxanthine (7464-84-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 35℃; for 3h;	78%

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + allyl bromide (106-95-6) → 7-Allyl-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione (102284-67-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 35℃; for 4h;	72%

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + propargyl bromide (106-96-7) → 3-isobutyl-1-methyl-7-propargylxanthine (58481-31-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 35℃; for 24h;	70%

2,2-dimethylpropyl bromide (630-17-1) + 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 7-(2,2-Dimethyl-propyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide 1.) 1 h, 2.) reflux, 8 h;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + tetramethyl ammoniumhydroxide (75-59-2) → C10H13N4O2(1-)*C4H12N(1+)

Conditions	Yield
In methanol; N,N-dimethyl-formamide for 0.0833333h;

1,2,3,5-tetra-O-acetyl-D-ribofuranose (28708-32-9) + 3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → Acetic acid (2R,3R,4R,5R)-4-acetoxy-5-acetoxymethyl-2-(3-isobutyl-1-methyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-tetrahydro-furan-3-yl ester (215647-97-5)

Conditions	Yield
With benzenesulfonamide; trimethylsilyl trifluoromethanesulfonate; Me2SiCl 2.) 1,2-dichloroethane, 60 deg C, 2 h; Yield given. Multistep reaction;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + XCH2-p-Cl-C6H4 → 7-(4-chloro-benzyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione (58481-29-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + XCH2Ph → 7-Benzyl-3-isobutyl-1-methylxanthine (58481-23-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + XCH2COOH → (3-isobutyl-1-methyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-acetic acid (68006-09-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + XCH2CHOHCH2OH → 7-(2,3-Dihydroxy-propyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione (132560-20-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + XCH(OMe)2 → 7-Dimethoxymethyl-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione (132560-17-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + XCH2CH(OCH2)2 → 7-[1,3]Dioxolan-2-ylmethyl-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione (132560-19-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + X(CH2)2COOH → 3-(3-Isobutyl-1-methyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-propionic acid (132560-21-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) + X(CH2)2CH(OEt)2 → 7-(3,3-Diethoxy-propyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione (132560-18-0)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20 - 80℃;

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 1-methyl-3-isobutyl-8-bromoxanthine (63908-35-0)

Conditions	Yield
With bromine; sodium acetate; acetic acid

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 7-benzyl-8-bromo-3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione (63908-34-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: Br2; NaOAc; AcOH 2: K2CO3 / dimethylformamide View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 7-benzyl-8-cyclopentylamino-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: Br2; NaOAc; AcOH 2: K2CO3 / dimethylformamide 3: iPr2NEt / 1-methyl-pyrrolidin-2-one / 160 °C View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 7-benzyl-8-cyclohexylamino-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: Br2; NaOAc; AcOH 2: K2CO3 / dimethylformamide 3: iPr2NEt / 1-methyl-pyrrolidin-2-one / 160 °C View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 7-((2R,3R,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) BSA, 2.) TMSOTf, Me2SiCl / 2.) 1,2-dichloroethane, 60 deg C, 2 h 2: NH3/MeOH View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 7-((2R,3R,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-3-isobutyl-1-methyl-8-methylamino-3,7-dihydro-purine-2,6-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) BSA, 2.) TMSOTf, Me2SiCl / 2.) 1,2-dichloroethane, 60 deg C, 2 h 2: 71 percent / NCS View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 7-((2R,3R,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-8-ethylamino-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) BSA, 2.) TMSOTf, Me2SiCl / 2.) 1,2-dichloroethane, 60 deg C, 2 h 2: 71 percent / NCS View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 8-Benzylamino-7-((2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) BSA, 2.) TMSOTf, Me2SiCl / 2.) 1,2-dichloroethane, 60 deg C, 2 h 2: 71 percent / NCS View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 7-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-8-chloro-1-methyl-3-isobutylxanthine (215647-99-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) BSA, 2.) TMSOTf, Me2SiCl / 2.) 1,2-dichloroethane, 60 deg C, 2 h 2: 71 percent / NCS View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 3-isobutylparaxanthine-7-(13CH3)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylformamide; methanol / 0.08 h 2: dimethylformamide; methanol / 2 h / Ambient temperature View Scheme

3,7-dihydro-1-methyl-3-(2-methylpropyl)-1H-purine-2,6-dione (28822-58-4) → 1-methyl-7-propyl-3-isobutylxanthine (102284-66-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / K2CO3 / dimethylformamide / 24 h / 35 °C 2: 83 percent / H2 / 10percent Pd/C / ethanol / 0.33 h / 2068.6 Torr View Scheme

Upstream product

• 54052-67-4 1-isobutyl-3-methyl-5-nitroso-6-amino uracil 
• 38014-54-9 1-isobutyl-3-methyl-urea 
• 58481-39-3 6-amino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione 
• 69150-36-3 1-methyl-7-<(pivaloyloxy)methyl>xanthine 
• 6136-37-4 1-methylxanthine 
• 70404-25-0 7-benzyl-1-methyl-3,7-dihydro-purine-2,6-dione 
• 58481-23-5 7-Benzyl-3-isobutyl-1-methylxanthine 
• 73018-01-6 7-Pivalyloxymethyl-1-methyl-3-isobutylxanthine 
• 64-18-6 formic acid 
• 78033-18-8 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione 

Downstream Products

• 69-89-6 xanthin 
• 132560-18-0 7-(3,3-Diethoxy-propyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione 
• 132560-21-5 3-(3-Isobutyl-1-methyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-propionic acid 
• 132560-17-9 7-Dimethoxymethyl-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione 
• 132560-20-4 7-(2,3-Dihydroxy-propyl)-3-isobutyl-1-methyl-3,7-dihydro-purine-2,6-dione 
• 68006-09-7 (3-isobutyl-1-methyl-2,6-dioxo-1,2,3,6-tetrahydro-purin-7-yl)-acetic acid 
• 7464-84-8 3-isobutyl-Paraxanthine 
• 63908-34-9 7-benzyl-8-bromo-3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione 
• 58481-23-5 7-Benzyl-3-isobutyl-1-methylxanthine 

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