28822-58-4

Usage

Uses

Used in Pharmaceutical and Research Applications:
3-Isobutyl-1-methylxanthine is used as a phosphodiesterase inhibitor for increasing the intracellular concentration of cAMP, which in turn activates protein kinase A (PKA). This makes it a valuable tool in various research and pharmaceutical applications, including the study of signal transduction pathways and the development of drugs targeting these pathways.
Used in Melanogenesis Research:
IBMX is used as a positive control in melanogenesis research, as it can induce the production of melanin, the pigment responsible for skin, hair, and eye color. This application is particularly relevant in the study of skin pigmentation disorders and the development of treatments for conditions such as vitiligo.
Used in Oocyte Research:
In oocyte research, 3-Isobutyl-1-methylxanthine is used to maintain the germinal vesicle (GV) arrest of prophase I oocytes. This application is crucial for the study of oocyte maturation and development, as well as for assisted reproductive technologies.
Used in Inhibition of Phenylephrine-Induced Release of 5-Hydroxytryptamine:
IBMX is used in the inhibition of phenylephrine-induced release of 5-hydroxytryptamine from neuroendocrine epithelial cells of the airway mucosa, with an IC50 of 1.3 μM. This application is important in the study of airway inflammation and the development of treatments for respiratory disorders.
Used in Inhibition of Ion Channels:
3-Isobutyl-1-methylxanthine also inhibits ion channels in the neuromuscular junction, GH3 cells, and vascular smooth muscle cells. This makes it a useful tool in the study of ion channel function and the development of treatments for neurological and cardiovascular disorders.
Used in Anticancer Applications:
IBMX is used to inhibit the growth of carcinoma cells both in vivo and in vitro in mice. Its ability to inhibit cancer cell growth makes it a potential candidate for the development of anticancer drugs and therapies.

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

• 64-18-6 formic acid 
• 78033-18-8 5,6-diamino-1-isobutyl-3-methyl-1H-pyrimidine-2,4-dione 
• 58481-23-5 7-Benzyl-3-isobutyl-1-methylxanthine 
• 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 
• 73018-01-6 7-Pivalyloxymethyl-1-methyl-3-isobutylxanthine 

Downstream Products

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

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