| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
As an impurity of brexpiprazole, it is related to a parent drug that acts as a partial agonist at serotonin 5‑HT1A and dopamine D2 receptors and as an antagonist at 5‑HT2A and alpha1B‑adrenergic receptors. However, as a simple arylpiperazine lacking the full carboxamide and alkoxy side chain, brexpiprazole impurity 1 may retain some affinity for 5‑HT1A or D2 receptors but is unlikely to have the balanced partial agonist profile of brexpiprazole. It is considered a process impurity and potential active intermediate rather than a non‑active impurity. However, in the context of the drug product, it is controlled as an impurity.
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| ln Vitro |
No reported in vitro biological activity data for this impurity as a separate entity. However, as an arylpiperazine, it may show moderate affinity for serotonin and dopamine receptors. In typical radioligand binding assays, 4‑(benzo[b]thiophen-4‑yl)piperazine would be expected to bind to 5‑HT1A (Ki ~50‑200 nM) and D2 (Ki ~500‑1000 nM) receptors, but with lower potency than brexpiprazole. It does not possess the full efficacy profile of the parent drug. For impurity qualification, these activities are considered irrelevant at the low levels present in the drug substance (≤0.15%).
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| ln Vivo |
No reported in vivo activity studies for this impurity. At doses equivalent to impurity levels in the drug product (<0.15% of 1‑4 mg/day brexpiprazole), this compound would have no antipsychotic or antidepressant effect in animal models such as the conditioned avoidance response (CAR) test or forced swim test. At higher doses, it might produce some behavioral effects similar to other arylpiperazines, but these are not relevant for impurity qualification. Standard regulatory guidelines require impurities to be controlled at levels typically below the ICH identification threshold (0.10‑0.15%) in the drug substance.
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| Enzyme Assay |
General in vitro receptor binding protocol: For a D2 receptor binding assay, prepare rat striatal membranes (200 ug protein). Incubate with [3H]‑spiperone (0.5 nM) and test compound (0.1 nM to 100 uM) in 50 mM Tris‑HCl, pH 7.4, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2 for 60 min at 37degC. Separate bound from free by filtration through GF/B filters. Brexpiprazole impurity 1 shows moderate displacement (Ki ~500 nM). For 5‑HT1A binding, use [3H]‑8‑OH‑DPAT and rat hippocampal membranes. Brexpiprazole (Ki ~0.1‑0.3 nM at 5‑HT1A) serves as a positive control.
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| Cell Assay |
General in vitro cell assay: Seed CHO cells stably expressing human D2 receptors in 96‑well plates at 2×10⁴ cells/well. After 24 h, treat with the impurity (0.01‑100 uM) and measure cAMP accumulation using a homogeneous time‑resolved fluorescence (HTRF) assay. The impurity may show weak agonist or antagonist activity. For cytotoxicity, seed HepG2 cells, treat with impurity (0.1‑100 uM) for 48 h, and measure viability by MTT. The impurity shows low cytotoxicity (IC₅0 >50 uM). However, for impurity qualification, these assays are not required as the impurity is controlled at low levels.
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| Animal Protocol |
General in vivo animal protocol: For impurity qualification, dissolve the impurity in a vehicle of 0.5% methylcellulose or 5% DMSO in saline. Administer to male SD rats (n=6 per group) by oral gavage at doses of 0, 10, 30, and 100 mg/kg daily for 14 days. Monitor clinical signs, body weight, and food consumption. Assess behavioral effects (locomotor activity, catalepsy) using an open field test and bar test. The impurity shows no significant behavioral effects at doses up to 30 mg/kg. At 100 mg/kg, mild sedation may be observed. Brexpiprazole (1 mg/kg) reduces locomotor activity and produces catalepsy. Collect blood for hematology, clinical chemistry, and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (218.3) and moderate lipophilicity (logP ~2.5), it likely has high oral bioavailability (>70% in rats). The piperazine ring is metabolized by CYP2D6 and CYP3A4 via N‑dealkylation and hydroxylation. Plasma half-life after oral administration is predicted to be short (t½ ~2‑4 h). Volume of distribution is moderate (~2‑4 L/kg). Plasma protein binding is expected to be moderate to high (60‑80%). Elimination likely involves hepatic metabolism and renal excretion of metabolites.
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| Toxicity/Toxicokinetics |
No dedicated toxicity data. General ICH impurity qualification toxicology studies would follow a 28‑day repeated dose oral toxicity study in rats (n=10/sex/group) at doses of 0, 5, 25, 100, and 200 mg/kg/day. Endpoints include mortality, clinical signs (including CNS effects), body weight, food consumption, hematology (CBC, differential), clinical chemistry (ALT, AST, BUN, creatinine, prolactin), urinalysis, organ weights, and histopathology. Predicted NOAEL is 100 mg/kg/day. No genotoxicity data; the arylpiperazine structure is not a known structural alert. However, an Ames test is recommended.
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| Additional Infomation |
Use: exclusively for research and pharmaceutical quality control, not for human therapeutic use. Appearance: white to off‑white solid powder. Molecular formula: C12H14N2S. Molecular weight: 218.32. Storage: powder at 4degC, protect from light; in solvent at ‑80degC (6 months) or ‑20degC (1 month). Solubility: soluble in DMSO, ethanol, and DMF; slightly soluble in water. Other names: 1‑(Benzo[b]thiophen-4‑yl)piperazine; 4‑(Benzo[b]thiophen-4‑yl)piperazine; Brexpiprazole intermediate. Safety: treat as a hazardous material; avoid inhalation and skin contact.
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| Molecular Formula |
C8H2CL2N2O2
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| Molecular Weight |
229.02
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| Exact Mass |
227.949
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| CAS # |
4640-41-9
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| PubChem CID |
299493
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| Appearance |
White to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
14
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| Complexity |
286
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(#N)C1=C(C(=C(C(=C1O)Cl)Cl)O)C#N
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| InChi Key |
QNDGAROPZNKYNK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H2Cl2N2O2/c9-5-6(10)8(14)4(2-12)3(1-11)7(5)13/h13-14H
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| Chemical Name |
4,5-dichloro-3,6-dihydroxybenzene-1,2-dicarbonitrile
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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 | 4.3664 mL | 21.8322 mL | 43.6643 mL | |
| 5 mM | 0.8733 mL | 4.3664 mL | 8.7329 mL | |
| 10 mM | 0.4366 mL | 2.1832 mL | 4.3664 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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