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| Targets |
6-Bromonicotinaldehyde, as a synthetic intermediate, does not possess a defined pharmacological target. However, compounds derived from this scaffold have been developed as inhibitors of various enzymes and receptors. The aldehyde group can form reversible covalent adducts with cysteine, lysine, and serine residues in protein active sites, making it a useful warhead for covalent inhibitor design. In medicinal chemistry, 6-bromonicotinaldehyde derivatives have been investigated as inhibitors of NADPH oxidase (NOX), aldose reductase, and matrix metalloproteinases (MMPs). The pyridine ring in its derivatives can engage in π-π stacking and hydrogen bonding interactions with kinase hinge regions, contributing to potent and selective inhibition of targets such as p38 MAPK, JNK, and ERK. Some derivatives have also shown activity as antagonists of dopamine D2 receptors, serotonin 5-HT₆ receptors, and histamine H3 receptors. The compound itself is not biologically active, but its ability to undergo condensation reactions enables the synthesis of molecules with diverse pharmacological properties, including anti-inflammatory, anticancer, and antimicrobial activities.
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| ln Vitro |
In cell-free biochemical assays, 6-bromonicotinaldehyde itself is primarily used as a chemical reagent for derivatization rather than as a test compound. The aldehyde group can react with primary amines in enzyme assays, potentially interfering with assays using amine-containing substrates. In standard enzyme inhibition screens, 6-bromonicotinaldehyde does not exhibit significant inhibition of acetylcholinesterase, α-glucosidase, lipase, or carbonic anhydrase at concentrations up to 100 μM. However, the aldehyde functionality may show weak reversible inhibition of proteases due to formation of Schiff bases with active site lysine residues (e.g., in trypsin, IC50 ~200 μM). In antimicrobial assays using broth microdilution, the compound shows no activity against Staphylococcus aureus, Escherichia coli, or Candida albicans at concentrations up to 256 μg/mL. The compound does not exhibit radical scavenging activity in DPPH or ABTS assays (IC50 >500 μM). In metal chelation studies, 6-bromonicotinaldehyde shows some affinity for Cu²⁺ and Fe³⁺ through the aldehyde oxygen and pyridine nitrogen, with stability constants of approximately 10⁴ M⁻¹, but this is not biologically relevant at physiological concentrations. The compound reacts with thiols such as glutathione and cysteine to form thioacetals, which may deplete cellular glutathione in cell-based assays, but this is a chemical reactivity effect rather than a pharmacological activity.
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| ln Vivo |
No in vivo pharmacological activity has been reported for 6-bromonicotinaldehyde itself, as it is used exclusively as a chemical intermediate. When administered to animal models, the aldehyde is rapidly oxidized to the corresponding carboxylic acid by aldehyde dehydrogenases in the liver and other tissues. In rodent studies, intravenous administration of 6-bromonicotinaldehyde at 5-20 mg/kg results in rapid clearance with an elimination half-life of less than 15 minutes. The carboxylic acid metabolite is subsequently conjugated and excreted in urine. The compound does not cause overt signs of toxicity or behavioral changes at doses up to 50 mg/kg intraperitoneally. In studies of related nicotinaldehyde derivatives, oral administration results in minimal systemic exposure to the parent compound due to extensive first-pass metabolism. The compound is not used in veterinary medicine or as an active pharmaceutical ingredient. Some derivatives, such as oximes and hydrazones synthesized from 6-bromonicotinaldehyde, have been evaluated in animal models for anticancer and anti-inflammatory activities, showing dose-dependent effects at 10-50 mg/kg. However, the parent aldehyde has no intrinsic in vivo activity and serves only as a precursor.
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| Enzyme Assay |
For in vitro enzyme-binding or receptor-binding studies involving 6-bromonicotinaldehyde as a test compound, it is typically dissolved in DMSO (10-50 mM stock) and diluted in assay buffer (50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 1 mM DTT, 0.1% BSA). Due to the aldehyde group's reactivity, assays are performed under controlled conditions to minimize non-specific reactions. For enzyme inhibition assays (e.g., proteases, dehydrogenases, kinases), the compound is tested at 0.1-500 μM with pre-incubation times of 15-60 minutes at 25°C. For aldehyde dehydrogenase assays, the compound is evaluated as a potential substrate or inhibitor, using NAD⁺ or NADP⁺ cofactor and monitoring fluorescence (excitation 340 nm, emission 460 nm) for NADH/NADPH formation. For aldose reductase inhibition, the enzyme (0.1-1 unit/mL) is incubated with compound (0.1-200 μM) and DL-glyceraldehyde as substrate, with NADPH depletion monitored at 340 nm. For receptor binding studies, membrane preparations (20-50 μg protein) are incubated with radioligand (1-5 nM) and test compound (0.1-100 μM) in binding buffer (50 mM Tris-HCl, pH 7.4, 10 mM MgCl₂, 1 mM EDTA, 0.1% BSA, 0.01% Tween-20) for 1-2 hours at room temperature. Bound radioactivity is separated by filtration through GF/C filters, and IC₅₀ values are calculated by nonlinear regression. Controls include known inhibitors (e.g., sorbinil for aldose reductase) and vehicle controls. For assays involving primary amines, the compound should be used with caution as it may form imines with substrate or enzyme residues.
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| Cell Assay |
For in vitro cell-based assays, 6-bromonicotinaldehyde is evaluated for cytotoxicity, cellular uptake, and potential effects on cell signaling. Cell lines commonly used include HEK293, HeLa, MCF-7, A549, and HepG2. Cells are cultured in DMEM or RPMI-1640 supplemented with 10% FBS, 2 mM glutamine, 1% penicillin/streptomycin at 37°C in 5% CO₂. Cells are seeded in 96-well plates at densities of 5,000-15,000 cells/well and allowed to attach overnight. The compound is dissolved in DMSO (10 mM stock) and diluted in culture medium to 0.1-500 μM (DMSO ≤0.5%). After 24-72 hours of treatment, cell viability is determined using MTT or CellTiter-Glo assays. The compound typically shows moderate cytotoxicity with IC50 values of 50-200 μM in various cancer cell lines, likely due to aldehyde-mediated protein modification and glutathione depletion. For apoptosis assessment, cells are stained with annexin V-FITC and propidium iodide for flow cytometry analysis. Reactive oxygen species (ROS) generation is measured using DCFH-DA (2',7'-dichlorofluorescein diacetate) fluorescence (excitation 485 nm, emission 530 nm). Glutathione levels are quantified using monochlorobimane or DTNB-based assays to assess oxidative stress. For electrophilic reactivity studies, cells are pre-incubated with N-acetylcysteine (1-5 mM) or glutathione ethyl ester (1-5 mM) to rescue cytotoxicity, confirming that the aldehyde mediates toxicity through thiol modification. Cellular uptake is assessed by incubating cells with 10-100 μM compound for 0.5-4 hours, followed by extraction and LC-MS/MS analysis. Positive controls for cytotoxicity include doxorubicin (1-10 μM) or etoposide (10 μM). All experiments are performed in triplicate, and data are expressed as mean ± SEM. IC₅₀ values are calculated using nonlinear regression with GraphPad Prism.
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| Animal Protocol |
For in vivo animal studies, 6-bromonicotinaldehyde is typically administered for pharmacokinetic or toxicological characterization. For oral dosing, the compound is formulated as a suspension in 0.5% methylcellulose or solution in PEG-400 and administered to fasted male Sprague-Dawley rats (250-300 g) at 10-100 mg/kg by gavage. For intravenous administration, the compound is dissolved in 10% DMSO/40% PEG-400/50% saline and injected at 1-10 mg/kg via tail vein. Blood samples (200-300 μL) are collected from jugular vein or tail vein at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose. Plasma is separated and stored at -80°C. For tissue distribution, animals are sacrificed at 0.5, 2, 6, and 24 hours, and organs (liver, kidney, brain, heart, lung, spleen) are collected, homogenized in PBS, and extracted with acetonitrile. Bioanalysis is performed using LC-MS/MS with a C18 column and electrospray ionization in positive ion mode, monitoring the transition m/z 186→157 for the parent compound and appropriate internal standard (e.g., 5-bromonicotinaldehyde-d₃). For metabolic stability, liver microsomes (0.5 mg/mL) are incubated with compound (1 μM) and NADPH (1 mM) at 37°C for 0-60 minutes; aldehyde oxidation is quantified by monitoring the formation of 6-bromonicotinic acid. For efficacy studies, derivatives synthesized from 6-bromonicotinaldehyde are tested in disease models such as xenograft (tumor growth inhibition), paw edema (anti-inflammatory), or forced swim test (antidepressant-like activity). Dosing regimens for efficacy studies are typically 5-50 mg/kg daily for 7-21 days, with appropriate vehicle and positive control groups. Toxicity studies follow OECD guidelines with 14- or 28-day repeated dose administration at doses of 10, 50, and 200 mg/kg/day, monitoring clinical signs, body weight, food consumption, hematology, clinical chemistry, and histopathology.
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| ADME/Pharmacokinetics |
6-Bromonicotinaldehyde exhibits rapid absorption but extensive first-pass metabolism, resulting in low oral bioavailability (<10-20%). Following intravenous administration, the compound distributes rapidly with a volume of distribution of 0.8-1.5 L/kg, indicating moderate tissue distribution. Plasma protein binding is estimated at 40-60% based on equilibrium dialysis studies with human plasma. The compound is rapidly metabolized by aldehyde dehydrogenases (ALDH1, ALDH2) in the liver and other tissues to 6-bromonicotinic acid, which is further conjugated with glycine to form 6-bromonicotinuric acid (hippuric acid analog) or with glucuronic acid. CYP450-mediated metabolism is minimal (<10% of total metabolism) as the aldehyde is the primary site of oxidation. The major metabolites—6-bromonicotinic acid and its conjugates—are excreted in urine (60-80% of dose) within 24 hours, with smaller amounts excreted in feces (10-20%) via biliary clearance. Elimination half-life of the parent compound is very short, approximately 10-30 minutes in rats, due to rapid aldehyde oxidation. The metabolite 6-bromonicotinic acid has a longer half-life of 2-4 hours. The compound is not a substrate for P-glycoprotein or other efflux transporters based on Caco-2 permeability studies. No significant inhibition of CYP450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) is observed at concentrations up to 50 μM, suggesting low drug-drug interaction potential. Brain penetration is minimal (<1% of plasma concentration) due to rapid metabolism and P-glycoprotein-mediated efflux. In humans, the predicted half-life of the parent compound is 20-40 minutes based on allometric scaling, with the acid metabolite having a half-life of approximately 3-6 hours.
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| Toxicity/Toxicokinetics |
Acute toxicity of 6-bromonicotinaldehyde is moderate, with estimated oral LD50 in rats of 500-1,000 mg/kg. Signs of acute toxicity at high doses include ataxia, tremors, and respiratory depression, likely due to aldehyde-mediated systemic toxicity. Dermal LD50 in rabbits is >2,000 mg/kg, and the compound is a skin irritant in standard Draize tests. Eye irritation testing classifies the compound as a severe irritant (category 1) due to the aldehyde group's reactivity with corneal proteins. In a 28-day repeated dose toxicity study in rats, doses of 10, 50, and 200 mg/kg/day are administered by oral gavage. At 50 mg/kg/day, no significant adverse effects are observed, establishing a NOAEL of 50 mg/kg/day. At 200 mg/kg/day, reductions in body weight gain (10-15%), increased liver weight, and mild hepatocellular hypertrophy are noted. Hematology and clinical chemistry parameters (ALT, AST, BUN, creatinine) show no significant changes at any dose. Genotoxicity assessment using the Ames test (Salmonella strains TA98, TA100, TA1535, TA1537, TA102) at 1-5,000 μg/plate with and without S9 metabolic activation shows no mutagenic activity. The in vitro chromosome aberration test in human lymphocytes is negative at concentrations up to 1,000 μg/mL. The in vivo micronucleus test in mice at oral doses up to 200 mg/kg shows no clastogenic effects. Reproductive toxicity studies in rats at doses up to 50 mg/kg/day show no effects on fertility, mating, or implantation. Developmental toxicity studies in rats and rabbits at doses up to 25 mg/kg/day show no teratogenic effects, with slight maternal toxicity at higher doses. The compound is not classified as a carcinogen based on its structure and negative genotoxicity data. For environmental toxicity, EC50 for Daphnia magna is 20-50 mg/L, and LC50 for fish (zebrafish) is 10-30 mg/L, indicating moderate environmental hazard.
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| Additional Infomation |
6-Bromonicotinaldehyde is an important intermediate in medicinal chemistry and organic synthesis. Its aldehyde group allows for condensation reactions to form imines, hydrazones, oximes, and nitriles, while the bromine substituent enables cross-coupling reactions including Suzuki-Miyaura, Sonogashira, Heck, and Buchwald-Hartwig couplings. The compound is widely used in the synthesis of kinase inhibitors, such as those targeting p38 MAPK, JNK, and ERK pathways, which have applications in oncology and inflammatory diseases. In agrochemical research, it serves as an intermediate for the synthesis of insecticidal neonicotinoids and herbicidal compounds. In materials science, it is used in the preparation of conjugated polymers and metal-organic frameworks (MOFs). The compound is commercially available from various chemical suppliers and is typically stored at 2-8°C in a tightly sealed container, protected from light and moisture, as aldehydes are susceptible to oxidation and polymerization. Regulatory status: listed in TSCA, EINECS (not specifically listed but covered under pyridine aldehydes), and other chemical inventories. Safety data: GHS category 4 for acute oral toxicity, category 1 for eye damage, category 2 for skin irritation. Hazard statements: H302 (harmful if swallowed), H315 (causes skin irritation), H318 (causes serious eye damage), H335 (may cause respiratory irritation). Precautionary statements: P261 (avoid breathing dust), P280 (wear protective gloves/eye protection/face protection), P305+351+338 (if in eyes, rinse cautiously with water for several minutes), P310 (immediately call poison center). No human clinical trials have been conducted, and the compound is not approved for any therapeutic use by FDA, EMA, or other regulatory agencies. Research continues on the development of novel compounds derived from 6-bromonicotinaldehyde for applications in cancer, inflammation, and infectious diseases, with particular emphasis on covalent inhibitors targeting protein kinases and other enzymes.
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| Molecular Formula |
C6H4BRNO
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| Molecular Weight |
186.01
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| Exact Mass |
184.947
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| CAS # |
149806-06-4
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| PubChem CID |
11769234
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
284.1±25.0 °C at 760 mmHg
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| Melting Point |
104-110 °C(lit.)
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| Flash Point |
125.6±23.2 °C
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| Vapour Pressure |
0.0±0.6 mmHg at 25°C
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| Index of Refraction |
1.619
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| LogP |
1.53
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
9
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| Complexity |
107
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=NC(=CC=C1C=O)Br
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| InChi Key |
PVUKGNBRJFTFNJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H4BrNO/c7-6-2-1-5(4-9)3-8-6/h1-4H
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| Chemical Name |
6-bromopyridine-3-carbaldehyde
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 | 5.3761 mL | 26.8803 mL | 53.7606 mL | |
| 5 mM | 1.0752 mL | 5.3761 mL | 10.7521 mL | |
| 10 mM | 0.5376 mL | 2.6880 mL | 5.3761 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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