| Targets |
The primary targets of this compound are likely to be similar to those of dronedarone, given their close structural similarity. Dronedarone, the parent drug, is a multi-channel blocker (Class III antiarrhythmic agent) that primarily targets cardiac ion channels, including potassium channels (IKr, IKs, IKur, and IK(ACh)), sodium channels (INa), and L-type calcium channels (ICa,L). It also exhibits antiadrenergic activity as a noncompetitive antagonist of beta1-adrenergic receptors. By extension, this intermediate may share similar channel- and receptor-binding properties, although it is not used therapeutically on its own.
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|---|---|
| ln Vitro |
In vitro studies on this specific intermediate are limited, as it is not a drug candidate itself. However, it serves as an important analytical standard for monitoring the quality and purity of dronedarone hydrochloride drug substance. In HPLC assays for dronedarone impurity profiling, the compound is used as a reference standard to identify and quantify trace levels of process-related impurities. In synthetic chemistry, its reactivity is well characterized: the nitro group can be reduced to an amino group, and the benzofuran core can undergo further functionalization.
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| ln Vivo |
In vivo activity is attributed not to the compound itself but to the parent drug dronedarone. Dronedarone exhibits antiarrhythmic efficacy in various animal models of atrial fibrillation. Studies in dogs, pigs, and rabbits have demonstrated that dronedarone reduces the inducibility of atrial fibrillation, prolongs atrial refractoriness, and suppresses atrial tachyarrhythmias without significant proarrhythmic effects. The in vivo effects are mediated through the blockade of multiple ion channels, which together prolong the cardiac action potential duration and refractory period.
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| Enzyme Assay |
Non-cellular experiments with this compound primarily involve HPLC-based analytical impurity profiling following ICH guidelines. A typical UPLC-ESI-MS/MS method uses a reverse-phase column (e.g., C18, 2.1 × 100 mm, 1.7 microm particles), with a mobile phase composed of ammonium formate buffer and acetonitrile delivered in a gradient elution program at a flow rate of 0.3 mL/min. Detection is performed by UV at 254 nm or by mass spectrometry in ESI positive mode. The compound is dissolved in methanol or acetonitrile to prepare reference standards at concentrations of 0.5-5 microg/mL for trace-level quantification.
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| Cell Assay |
Cell-based experiments for this compound are not typically performed, as it is an intermediate and impurity rather than a therapeutic agent. However, given its structural similarity to dronedarone, related benzofuran derivatives have been evaluated for cytotoxicity in hepatic cell lines (e.g., HepG2 cells) to assess safety profiles. Standard cytotoxicity assays would involve treating cells with increasing concentrations of the compound for 24-72 hours, followed by MTT or XTT reduction assays to measure cell viability and by lactate dehydrogenase (LDH) release assays to assess membrane integrity.
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| Animal Protocol |
In vivo animal experiments for this compound are not conducted as it is a synthetic intermediate. The parent drug dronedarone has been extensively evaluated in animal models. A typical study in beagle dogs involves oral administration of dronedarone at doses of 10-30 mg/kg. Electrophysiological parameters are assessed by ECG telemetry, while efficacy against atrial fibrillation is evaluated using burst pacing protocols. Dronedarone shows good oral bioavailability in dogs and effectively suppresses the inducibility of atrial fibrillation with a long duration of action.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties are associated with the parent drug dronedarone, not with this intermediate. Dronedarone is approximately 70-100% absorbed orally but has low bioavailability (4-15%) due to extensive first-pass metabolism. It is highly protein bound (>98%), primarily to albumin, and is metabolized predominantly by CYP3A4 in the liver to form N-debutyl and other metabolites. The elimination half-life ranges from 13 to 19 hours. Dronedarone is a substrate and inhibitor of P-glycoprotein. The intermediate compound itself is a solid with a melting point of 129.8-130.7degC, a density of 1.3+/-0.1 g/cm3, a boiling point of 559.5+/-50.0degC at 760 mmHg, and a flash point of 292.2+/-30.1degC.
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| Toxicity/Toxicokinetics |
The toxicity profile of this compound is not separately characterized, but the parent drug dronedarone is known to have a boxed warning for heart failure exacerbation, liver injury, and severe skin reactions (including Stevens-Johnson syndrome). As a research-use-only intermediate, standard chemical safety precautions apply: may cause skin and eye irritation, harmful if swallowed, and should be handled in a well-ventilated area with appropriate PPE. The compound is stable at room temperature but should be protected from light.
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| Additional Infomation |
Additional information: The compound has a purity level where impurities are typically controlled to <0.5% in pharmaceutical manufacturing. It is available for purchase from chemical suppliers as a reference standard for analytical and research applications only, not for human or veterinary use. Its synonyms include 2-butyl-3-(4-hydroxybenzoyl)-5-nitrobenzofuran, Dronedarone Related Compound D, and 2-butyl-5-nitro-1-benzofuran-3-yl)(4-hydroxyphenyl)methanone.
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| Molecular Formula |
C19H17NO5
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|---|---|
| Molecular Weight |
339.35
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| Exact Mass |
339.111
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| CAS # |
141645-16-1
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| PubChem CID |
11473234
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
483
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCC1=C(C2=C(O1)C=CC(=C2)[N+](=O)[O-])C(=O)C3=CC=C(C=C3)O
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| InChi Key |
ZJZKLBXEGZKOBW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17NO5/c1-2-3-4-17-18(19(22)12-5-8-14(21)9-6-12)15-11-13(20(23)24)7-10-16(15)25-17/h5-11,21H,2-4H2,1H3
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| Chemical Name |
(2-butyl-5-nitro-1-benzofuran-3-yl)-(4-hydroxyphenyl)methanone
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| Synonyms |
2-Butyl-5-nitro-3-(4-hydroxybenzoyl)benzofuran (Standard)
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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 | 2.9468 mL | 14.7341 mL | 29.4681 mL | |
| 5 mM | 0.5894 mL | 2.9468 mL | 5.8936 mL | |
| 10 mM | 0.2947 mL | 1.4734 mL | 2.9468 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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