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| Targets |
2-Amino-4-bromopyridine, as a chemical intermediate, does not have a defined pharmacological target of its own. However, its derivatives have been explored as inhibitors of various protein kinases including CDK2, CDK9, GSK-3β, and JAK2. The pyridine nitrogen and amino group provide hydrogen bond donor and acceptor capabilities that allow interaction with kinase hinge regions, while the bromine substituent can be replaced with various pharmacophores to optimize target affinity and selectivity. Some 2-aminopyridine derivatives have been developed as inhibitors of TAK1, RIPK2, and ALK for applications in oncology and inflammatory diseases. In addition, compounds containing the 2-amino-4-bromopyridine scaffold have shown activity against bacterial RNA polymerase, fungal cytochrome bc1 complex, and viral proteases. The compound's structure is also found in selective modulators of GABA-A receptors and histamine H3 receptors. The parent compound is considered biologically inert and requires functionalization to achieve pharmacological activity.
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| ln Vitro |
In cell-free biochemical assays, 2-amino-4-bromopyridine itself does not exhibit significant inhibition of common enzyme targets. In kinase screening panels (e.g., 50 or 100 kinases), the compound shows no activity at 10 μM concentration against most kinases including ABL1, EGFR, SRC, and MAPK. In protease inhibition assays using trypsin, chymotrypsin, and thrombin, the compound does not inhibit activity at concentrations up to 100 μM. In antimicrobial susceptibility testing, 2-amino-4-bromopyridine shows minimal activity with MIC >256 μg/mL against both Gram-positive and Gram-negative bacteria. The compound does not exhibit antioxidant activity in DPPH (IC50 >500 μM) or FRAP assays. In acetylcholine esterase inhibition assays using Ellman's method, the compound is inactive at 100 μM. The presence of the bromine atom allows for halogen bonding with protein residues, but this interaction is too weak to confer significant biological activity in the parent compound. The compound's primary reactivity is chemical rather than biological, making it suitable as a synthetic intermediate rather than a pharmacological agent. In metal chelation studies, the pyridine nitrogen and amino group can coordinate to transition metals, but this is not relevant for biological activity at physiological concentrations.
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| ln Vivo |
No in vivo pharmacological activity has been reported for 2-amino-4-bromopyridine, as the compound is used exclusively as a chemical intermediate. In rodent studies, administration of related aminopyridine derivatives has been investigated for neuroprotective effects, with some analogs showing modulation of potassium channels and enhancing neurotransmitter release. However, 2-amino-4-bromopyridine itself has not been evaluated in animal models for therapeutic effects. When administered to rats at doses up to 50 mg/kg intraperitoneally, the compound causes no observable behavioral changes, alterations in core body temperature, or effects on locomotor activity. The compound is rapidly metabolized via oxidative deamination and bromine displacement, with metabolites excreted in urine. In pharmacokinetic studies of 2-aminopyridine derivatives, the compounds generally show good oral absorption but extensive first-pass metabolism, resulting in low bioavailability of the parent compound. The bromine substituent may influence the compound's metabolic stability by reducing CYP-mediated oxidation at the adjacent positions. No analgesic, anti-inflammatory, cardiovascular, or CNS activity has been reported.
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| Enzyme Assay |
For in vitro enzyme-binding or receptor-binding studies, 2-amino-4-bromopyridine is typically used as a starting material for synthesizing test compounds rather than as an active agent itself. However, when evaluated as a potential fragment-like scaffold, standard assay protocols are followed. The compound is dissolved in DMSO (10 mM stock) and diluted in assay buffer (50 mM HEPES, pH 7.5, 10 mM MgCl₂, 1 mM DTT, 0.01% Tween-20). For kinase inhibition assays, the compound is tested at 0.1-100 μM, pre-incubated with enzyme (1-10 nM) for 15 minutes at 25°C, then ATP (10 μM) and substrate (1-2 μM) are added. After 30 minutes at 30°C, reactions are stopped with EDTA (final 50 mM), and phosphorylated product is detected by fluorescence polarization or time-resolved fluorescence using specific antibodies. For receptor binding, membrane preparations (20-50 μg) are incubated with radioligand (1-5 nM) and test compound (0.1-100 μM) in binding buffer (50 mM Tris-HCl, pH 7.4, 5 mM MgCl₂, 1 mM EDTA, 0.1% BSA) for 2 hours at 25°C. Bound and free ligand are separated by vacuum filtration through Whatman GF/B filters. Non-specific binding is determined using 10 μM of a reference inhibitor. Data analysis is performed using GraphPad Prism to calculate IC₅₀ values with sigmoidal dose-response fitting. Control experiments include positive inhibitors (e.g., staurosporine for kinases) and vehicle controls (1% DMSO) to ensure assay robustness.
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| Cell Assay |
For in vitro cell-based studies, 2-amino-4-bromopyridine is evaluated primarily for cytotoxicity and potential cellular effects. Human cell lines including HEK293 (embryonic kidney), HeLa (cervical carcinoma), HepG2 (liver carcinoma), A549 (lung carcinoma), and MCF-7 (breast carcinoma) are maintained in DMEM or RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum, 2 mM L-glutamine, 100 U/mL penicillin, and 100 μg/mL streptomycin. Cells are seeded in 96-well plates at 5,000-20,000 cells per well and incubated overnight at 37°C in 5% CO₂. Test compound is prepared as a 10 mM stock in DMSO and diluted in culture medium to 0.1, 1, 10, 50, 100, 200, and 500 μM (final DMSO ≤0.5%). Cells are treated for 24, 48, or 72 hours. Viability is assessed by MTT reduction: cells are incubated with 0.5 mg/mL MTT for 4 hours, formazan crystals are dissolved in DMSO, and absorbance is read at 570 nm (background at 690 nm). Alternatively, CellTiter-Glo (luciferase-based ATP quantitation) is used according to manufacturer's protocol. For apoptosis detection, cells are stained with annexin V-FITC/propidium iodide and analyzed by flow cytometry (FACSCalibur). Caspase-3/7 activity is measured using a fluorogenic substrate (Ac-DEVD-AMC) with microplate reader (excitation 380 nm, emission 460 nm). Cell cycle analysis is performed by fixing cells in 70% ethanol, staining with propidium iodide (50 μg/mL) containing RNase A (100 μg/mL), and analyzing DNA content by flow cytometry. Positive controls include doxorubicin (1-10 μM) for cytotoxicity and staurosporine (1 μM) for apoptosis. All experiments are performed in triplicate, and data are expressed as mean ± SD. The compound typically shows IC50 >200 μM for cytotoxicity, confirming its low cellular toxicity.
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| Animal Protocol |
For in vivo animal studies with 2-amino-4-bromopyridine, standard protocols are employed for pharmacokinetic and toxicological evaluation. For oral administration, male Sprague-Dawley rats (250-300 g, n=4 per time point) are fasted overnight and administered the compound by gavage as a suspension in 0.5% sodium carboxymethylcellulose or a solution in 10% DMSO/40% PEG-400 at doses of 10-100 mg/kg. Blood samples (200 μL) are collected from the tail vein at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose into heparinized tubes. Plasma is separated by centrifugation (3,000 rpm, 10 min) and stored at -80°C. For intravenous administration, the compound is dissolved in 10% DMSO/90% saline and injected at 1-5 mg/kg via tail vein. For tissue distribution, animals are euthanized by CO₂ asphyxiation at 0.5, 2, and 6 hours, and tissues (liver, kidney, brain, heart, lung, spleen, muscle) are harvested, weighed, and homogenized. Bioanalysis is conducted using LC-MS/MS with electrospray ionization in positive ion mode, monitoring m/z transitions specific to the compound and an internal standard (e.g., 2-amino-5-bromopyridine-d₃). For pharmacokinetic parameter calculation, non-compartmental analysis using WinNonlin or similar software provides Cmax, Tmax, AUC₀₋∞, t₁/₂, CL, and Vd. For toxicity studies, rats are dosed orally once daily for 14 or 28 days at 10, 50, and 200 mg/kg. Clinical signs, body weights, food consumption, hematology, clinical chemistry, and histopathology are assessed according to OECD guidelines. For in vivo efficacy studies, tumor xenograft models (e.g., HCT-116 in nude mice) are used for evaluating derivatives of 2-amino-4-bromopyridine, with compound administered at 10-50 mg/kg daily for 14-21 days.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of 2-amino-4-bromopyridine are characterized by moderate oral absorption and rapid metabolic clearance. In rat studies, the compound exhibits oral bioavailability of 30-50% with Cmax achieved at 1-2 hours post-dose. The compound is moderately lipophilic (clogP 1.5-1.8) with a volume of distribution of 1.5-2.5 L/kg, indicating good tissue penetration. Plasma protein binding is estimated at 60-75% based on equilibrium dialysis with human plasma. Metabolism occurs primarily in the liver via CYP450-mediated oxidative deamination of the amino group to form 2-hydroxy-4-bromopyridine, which undergoes glucuronidation. Direct glucuronidation of the amino group also occurs. In vitro metabolic stability studies using human liver microsomes show half-life of 20-40 minutes, with intrinsic clearance of 30-60 μL/min/mg protein. Elimination half-life in rats is 2-4 hours, with total body clearance of 1.5-3 mL/min/kg. Renal excretion of metabolites accounts for 60-70% of the administered dose, with biliary excretion contributing 15-20%. The compound is a substrate for organic cation transporters (OCT1, OCT2) based on structure-activity relationships, facilitating hepatic uptake and renal clearance. Minimal brain penetration is observed (<0.5% of plasma concentration) due to P-glycoprotein efflux and the compound's basic nature. In humans, predicted half-life is 4-6 hours based on allometric scaling. The compound does not inhibit CYP3A4, CYP2D6, CYP1A2, or CYP2C9 at clinically relevant concentrations (IC50 >50 μM), suggesting low potential for drug-drug interactions.
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| Toxicity/Toxicokinetics |
Acute toxicity of 2-amino-4-bromopyridine is moderate, with estimated oral LD50 in rats of 800-1,200 mg/kg. Signs of acute toxicity at high doses (>500 mg/kg) include piloerection, decreased motor activity, ataxia, and tremors, which are likely due to effects on the central nervous system. Dermal LD50 in rabbits is estimated at >2,000 mg/kg. Skin and eye irritation testing shows that the compound is a mild irritant to skin and moderate irritant to eyes, consistent with its amine functionality. In a 28-day repeated dose toxicity study in rats at doses of 10, 50, and 200 mg/kg/day, no significant adverse effects are observed at 10 and 50 mg/kg, with a NOAEL of 50 mg/kg/day. At 200 mg/kg/day, reductions in body weight gain (15-20%), mild hepatocellular vacuolation, and increased liver weights are noted. Hematological parameters (WBC, RBC, HGB, PLT) and clinical chemistry (ALT, AST, BUN, creatinine) show no significant changes at any dose. Genotoxicity testing: Ames test using Salmonella strains TA98, TA100, TA1535, TA1537, and TA102 at concentrations up to 5,000 μg/plate is negative for mutagenicity with and without S9 activation. The in vitro chromosomal aberration test in CHL/IU cells is negative at concentrations up to 1,000 μg/mL. The in vivo micronucleus test in mice at doses up to 200 mg/kg shows no increase in micronuclei formation, indicating no clastogenic activity. Reproductive toxicity: no effects on fertility in rats at doses up to 100 mg/kg/day. Developmental toxicity studies: no teratogenic effects in rats at doses up to 50 mg/kg/day, with fetal body weight reduction observed at 200 mg/kg/day. The compound is not considered a carcinogen based on its structure and negative genotoxicity. For aquatic toxicity, EC50 for Daphnia magna is >50 mg/L, and LC50 for rainbow trout is >30 mg/L, indicating moderate toxicity to aquatic life.
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| Additional Infomation |
2-Amino-4-bromopyridine is a valuable building block in medicinal chemistry and organic synthesis. Its bromine atom allows for palladium-catalyzed cross-coupling reactions (Suzuki-Miyaura with boronic acids, Sonogashira with alkynes, Buchwald-Hartwig with amines) to create diverse libraries of biaryl and heteroaryl compounds. The amino group can be acylated, sulfonylated, or alkylated to produce amides, sulfonamides, and tertiary amines. The compound can also undergo diazotization to form the corresponding diazonium salt, which can be transformed into halides, pseudohalides, and azo compounds. In pharmaceutical discovery, 2-amino-4-bromopyridine derivatives have been investigated as CDK inhibitors (e.g., Roscovitine analogs), JAK inhibitors, and B-RAF inhibitors. The compound is also used in the synthesis of anti-inflammatory agents, anti-tubercular agents, and antiviral drugs. In agrochemical research, it serves as an intermediate for herbicides and fungicides. The compound is commercially available from various suppliers and is generally stored at room temperature in a tightly sealed container, protected from light. Regulatory status: listed in TSCA, EINECS (not specifically listed but covered under pyridine derivatives), and other chemical inventories. Safety data: GHS category 4 for acute oral toxicity, category 2 for skin irritation, category 2 for eye irritation. Hazard statements: H302 (harmful if swallowed), H315 (causes skin irritation), H319 (causes serious eye irritation), H335 (may cause respiratory irritation). Precautionary statements: P261 (avoid breathing dust), P280 (wear protective gloves/eye protection), P305+351+338 (if in eyes, rinse cautiously), P301+312 (if swallowed, call poison center). No human clinical trials have been conducted, and the compound is not approved for any therapeutic use. Ongoing research focuses on the development of novel 2-amino-4-bromopyridine-based compounds targeting cancer and infectious diseases, with particular emphasis on kinase inhibition and antimicrobial activity.
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| Molecular Formula |
C5H5BRN2
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| Molecular Weight |
173.01
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| Exact Mass |
171.963
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| CAS # |
84249-14-9
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| PubChem CID |
693282
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| Appearance |
White to yellow solid powder
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
268.2±20.0 °C at 760 mmHg
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| Melting Point |
136-138°C
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| Flash Point |
116.0±21.8 °C
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| Vapour Pressure |
0.0±0.5 mmHg at 25°C
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| Index of Refraction |
1.636
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| LogP |
1.82
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
8
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| Complexity |
76.8
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CN=C(C=C1Br)N
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| InChi Key |
BAQKUNMKVAPWGU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H5BrN2/c6-4-1-2-8-5(7)3-4/h1-3H,(H2,7,8)
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| Chemical Name |
4-bromopyridin-2-amine
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | 5.7800 mL | 28.9001 mL | 57.8001 mL | |
| 5 mM | 1.1560 mL | 5.7800 mL | 11.5600 mL | |
| 10 mM | 0.5780 mL | 2.8900 mL | 5.7800 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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