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| Targets |
1H-Pyrazole-4-boronic acid pinacol ester is a chemical reagent and does not directly target biological receptors or enzymes. Its role in biological research is indirect: it is used as a synthetic intermediate in the preparation of pharmacologically active compounds, particularly kinase inhibitors. It has been employed as a reagent for preparing inhibitors of various therapeutic targets, including VEGF (vascular endothelial growth factor), Aurora kinases, RHO (ROCK), Janus Kinase 2 (JAK2), c-MET, ALK, CDC7, and Acetyl-CoA carboxylase. The boronic acid pinacol ester group is a protecting group for the boronic acid functionality, which participates in transmetalation during Suzuki-Miyaura cross-coupling. Upon deprotection, the resulting boronic acid can bind to the active site serine of certain enzymes (e.g., proteasome), but this is not the intended use for this intermediate.
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| ln Vitro |
As a synthetic reagent, 1H-Pyrazole-4-boronic acid pinacol ester does not possess intrinsic in vitro biological activity. It is not used in cell-based assays to directly modulate biological functions. However, it is an essential building block for the synthesis of compounds that exhibit potent in vitro activities. For example, it has been used in the synthesis of JAK2 inhibitors for the treatment of myeloproliferative disorders, and such inhibitors (e.g., ruxolitinib analogs) have IC50 values in the low nanomolar range in cellular assays. Similarly, it has been used to prepare Aurora kinase inhibitors with antiproliferative activity in cancer cell lines. The in vitro activity, therefore, depends entirely on the final synthesized compound, not on this intermediate itself. Researchers use this reagent to assemble complex drug-like molecules via cross-coupling chemistry.
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| ln Vivo |
1H-Pyrazole-4-boronic acid pinacol ester is not administered in vivo and does not exhibit in vivo biological activity. Its purpose is strictly as a chemical reagent for organic synthesis. The compounds that are synthesized using this intermediate may have significant in vivo activities. For example, JAK2 inhibitors prepared using this reagent have shown efficacy in mouse models of myeloproliferative neoplasms, reducing splenomegaly and improving hematocrit levels. Similarly, ROCK inhibitors synthesized from this building block have demonstrated antihypertensive effects in rodent models, and Aurora kinase inhibitors have shown tumor growth inhibition in xenograft models. The in vivo activity of the final drug candidate is unrelated to the boronic acid ester intermediate beyond its structural contribution. This reagent is not intended for therapeutic applications.
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| Enzyme Assay |
A typical non-cellular protocol for using 1H-Pyrazole-4-boronic acid pinacol ester involves its use in a Suzuki-Miyaura cross-coupling reaction. In a microwave vial or round-bottom flask, the boronic acid pinacol ester (1.0 equiv, e.g., 1 mmol, 194 mg) and an aryl or heteroaryl halide (e.g., bromopyridine, 1.0 equiv) are combined in a solvent mixture of 1,4-dioxane and water (4:1, 5 mL). A base such as potassium carbonate (K2CO3, 2-3 equiv) is added, followed by a palladium catalyst (e.g., Pd(PPh3)4, 5 mol% or Pd(dppf)Cl2, 2-5 mol%). The reaction mixture is degassed by bubbling nitrogen or argon for 10-15 minutes. The mixture is then heated to 80-100degC for 2-12 hours, depending on the substrates. The progress of the reaction is monitored by TLC or LC-MS. After completion, the mixture is cooled, diluted with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The crude product is purified by flash column chromatography on silica gel to yield the cross-coupled product. The reaction can be scaled up to multi-gram quantities.
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| Cell Assay |
Since 1H-Pyrazole-4-boronic acid pinacol ester is a chemical reagent, it is not used directly in cell culture. However, after it has been incorporated into a biologically active molecule via cross-coupling, that final molecule can be tested in cell-based assays. A typical protocol for testing the anticancer activity of a pyrazole-containing compound synthesized from this reagent uses A549 lung cancer cells. Cells are seeded in 96-well plates at 5×103 cells/well in DMEM with 10% FBS and 1% penicillin/streptomycin, and cultured at 37degC in 5% CO2 overnight. The next day, the test compound (synthesized from 1H-Pyrazole-4-boronic acid pinacol ester) is dissolved in DMSO (10 mM stock) and diluted in culture medium to final concentrations ranging from 0.1 nM to 10 uM. Cells are treated for 48-72 hours. Cell viability is measured using an MTT assay (10 uL of 5 mg/mL MTT per well for 4 hours, followed by 100 uL of solubilization buffer, absorbance measured at 570 nm). The IC50 is calculated. For mechanism studies, cells are treated with the test compound for 24 hours, harvested, lysed, and analyzed by Western blot for target protein inhibition.
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| Animal Protocol |
The in vivo use of 1H-Pyrazole-4-boronic acid pinacol ester is limited to its incorporation into drug-like molecules via chemical synthesis. The synthesized compounds are then tested in animal models. A typical protocol for evaluating a kinase inhibitor prepared using this building block involves a xenograft model. Female NCr nu/nu mice (6-8 weeks old) are subcutaneously injected with 5×10⁶ cancer cells (e.g., A549 lung cancer cells) in 0.1 mL of PBS mixed 1:1 with Matrigel. When tumors reach approximately 150 mm3, mice are randomized into treatment groups (n=8-10 per group). The synthesized compound (e.g., a JAK2 inhibitor) is formulated in a suitable vehicle (e.g., 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline) and administered orally or intraperitoneally once daily at doses of 10-50 mg/kg. The vehicle control group receives the same volume of vehicle. Tumor volumes are measured twice weekly with calipers, and body weights are monitored. After 21-28 days, mice are euthanized, and tumors are harvested for histological analysis (H&E, Ki67 immunohistochemistry, TUNEL staining). The boronic acid ester reagent itself is not administered to animals.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for 1H-Pyrazole-4-boronic acid pinacol ester are not applicable because this compound is a synthetic intermediate and not a drug candidate. However, the compound has been characterized for its physicochemical properties. It is a solid with a melting point in the range of 140-150degC and has low solubility in water. It is soluble in organic solvents such as DMSO, DMF, and dichloromethane. The boronic acid pinacol ester group is stable under standard storage conditions but can be hydrolyzed to the corresponding boronic acid under acidic or aqueous conditions. The molecular weight is 194.04 g/mol. For synthetic applications, the compound is stable for months when stored at room temperature in a tightly sealed container. No further ADME parameters (absorption, distribution, metabolism, excretion) are relevant or reported.
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| Toxicity/Toxicokinetics |
1H-Pyrazole-4-boronic acid pinacol ester is a chemical reagent and, as such, should be handled with standard laboratory safety precautions. It is not intended for human or animal use. The compound is irritating to the eyes, respiratory system, and skin. Wear appropriate personal protective equipment (chemical-resistant gloves such as nitrile, safety goggles, and a lab coat). Use only in a well-ventilated area, preferably a chemical fume hood. Avoid inhalation of dust, contact with skin and eyes, and ingestion. Wash hands thoroughly after handling. In case of contact, rinse eyes or skin with plenty of water for at least 15 minutes and seek medical attention if irritation persists. The compound should be stored in a tightly sealed container in a cool, dry place, away from incompatible materials (e.g., oxidizing agents, acids). No acute or chronic toxicity data specific to this compound are available. It is for research use only and should not be used in humans or animals for therapeutic or diagnostic purposes.
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| Additional Infomation |
1H-Pyrazole-4-boronic acid pinacol ester is a boronic acid ester widely employed in Suzuki-Miyaura cross-coupling reactions for the construction of carbon-carbon bonds. Its molecular formula is C9H15BN2O2, and its molecular weight is 194.04 g/mol. The compound is also known as 1H-pyrazole-4-boronic acid pinacol ester or 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. It is available with a purity of typically 97.5-98%. The reagent is used in the preparation of various biologically active compounds, including inhibitors of VEGF, Aurora kinases, RHO (ROCK), Janus Kinase 2 (JAK2), c-MET, ALK, S-nitrosoglutathione reductase, CDC7, and Acetyl-CoA carboxylase. It is also used for ruthenium-catalyzed asymmetric hydrogenation. The compound is insoluble in water but soluble in common organic solvents. It is for research use only and is not an FDA-approved drug.
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| Molecular Formula |
C9H15BN2O2
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| Molecular Weight |
194.04
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| Exact Mass |
194.122
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| CAS # |
269410-08-4
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| PubChem CID |
2774010
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| Appearance |
White to light yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
335.4±15.0 °C at 760 mmHg
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| Melting Point |
142-146 °C(lit.)
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| Flash Point |
156.6±20.4 °C
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| Vapour Pressure |
0.0±0.7 mmHg at 25°C
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| Index of Refraction |
1.487
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| LogP |
0.708
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
217
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1B(C2C([H])=NN([H])C=2[H])OC(C([H])([H])[H])(C([H])([H])[H])C1(C([H])([H])[H])C([H])([H])[H]
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| InChi Key |
TVOJIBGZFYMWDT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H15BN2O2/c1-8(2)9(3,4)14-10(13-8)7-5-11-12-6-7/h5-6H,1-4H3,(H,11,12)
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| Chemical Name |
4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.1536 mL | 25.7679 mL | 51.5358 mL | |
| 5 mM | 1.0307 mL | 5.1536 mL | 10.3072 mL | |
| 10 mM | 0.5154 mL | 2.5768 mL | 5.1536 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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