| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Azimilide (NE-10064) is a class III antiarrhythmic agent acting as a potassium channel blocker. It can be potentially used for the treatment of arrhythmia. Azimilide inhibits I(Ks) and I(Kr) in guinea-pig cardiac myocytes and I(Ks) (minK) channels expressed in Xenopus oocytes.
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Oral absorption is excellent. Metabolism/Metabolites Azimilite undergoes a unique metabolic pathway in the human body, breaking down into two structurally different metabolites. One study showed that the cleavage metabolite 4-chloro-2-phenylfuranoic acid has a high plasma concentration, while other plasma metabolites, such as azimilite N-oxide and a cleaved hydantoin metabolite, have lower concentrations. In urine, the cleavage metabolite is the major metabolite (accounting for more than 35% of the dose), followed by phenols (in conjugated form, accounting for 7%-8%), azimilite N-oxide (4%-10%), a butyrate metabolite (2%-3%), and desmethylazimilite (2%). Preliminary investigation of fecal metabolites revealed the presence of azimilite (3%–5%), demethylazimilite (1%–3%), and butyrate metabolites (<1%). In vitro and in vivo studies identified the metabolic pathways of azimilite, including CYP1A1 (approximately 28%), 3A4/5 (approximately 20%), 2D6 (<1%), FMO (approximately 14%), and cleavage (35%). No enzymes involved in azimilite cleavage were identified. The known human metabolites of azimilit include 1-[(Z)-[5-(4-chlorophenyl)furan-2-yl]methyleneamino]-3-[4-(4-methyl-4-oxypiperazin-4-onth-1-yl)butyl]imidazolidine-2,4-dione and 1-[(E)-[5-(4-chlorophenyl)furan-2-yl]methyleneamino]-3-(4-piperazin-1-ylbutyl)imidazolidine-2,4-dione. |
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| References |
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| Additional Infomation |
Azimilite is an imidazolidine-2,4-dione compound. Azimilite is an investigational class III antiarrhythmic drug that blocks both the fast and slow components of delayed rectifier potassium channels. It is not currently approved for use in any country but is undergoing clinical trials in the United States. Drug Indications: Investigative treatment for arrhythmias and atrial fibrillation. Mechanism of Action: Azimilite's mechanism of action involves blocking both slow-conduction rectifier potassium currents (I(Ks)) and fast-conduction rectifier potassium currents (I(Kr)) in cardiomyocytes. This differs from other class III antiarrhythmic drugs, which typically block only I(Kr) or simultaneously block sodium, calcium, or transient outward potassium currents (I(to)). Azimilite also blocks sodium currents (I(Na)) and calcium currents (I(CaL)). Its effect on ventricular arrhythmias induced by reentrant circuits in the infarct borderline zone is unclear.
Pharmacodynamics Azimilit is a novel class III antiarrhythmic drug. Its characteristics include: relatively no adverse drug dependence, good oral absorption, no need for dose titration, outpatient initiation of treatment, no dose adjustment required in renal or hepatic failure, and no interaction with warfarin or digoxin. It carries a certain risk of torsades de pointes and, in rare cases, may cause neutropenia. |
| Molecular Formula |
C23H28N5O3CL
|
|---|---|
| Molecular Weight |
457.95312
|
| Exact Mass |
457.188
|
| CAS # |
149908-53-2
|
| Related CAS # |
Azimilide dihydrochloride;149888-94-8
|
| PubChem CID |
9571004
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| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.32 g/cm3
|
| Boiling Point |
594.9ºC at 760 mmHg
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| Flash Point |
313.6ºC
|
| LogP |
2.977
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
32
|
| Complexity |
677
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1N(CCCCN2CCN(C)CC2)C(CN1/N=C/C3=CC=C(C4=CC=C(Cl)C=C4)O3)=O
|
| InChi Key |
MREBEPTUUMTTIA-PCLIKHOPSA-N
|
| InChi Code |
InChI=1S/C23H28ClN5O3/c1-26-12-14-27(15-13-26)10-2-3-11-28-22(30)17-29(23(28)31)25-16-20-8-9-21(32-20)18-4-6-19(24)7-5-18/h4-9,16H,2-3,10-15,17H2,1H3/b25-16+
|
| Chemical Name |
1-[(E)-[5-(4-chlorophenyl)furan-2-yl]methylideneamino]-3-[4-(4-methylpiperazin-1-yl)butyl]imidazolidine-2,4-dione
|
| 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 | 2.1836 mL | 10.9182 mL | 21.8364 mL | |
| 5 mM | 0.4367 mL | 2.1836 mL | 4.3673 mL | |
| 10 mM | 0.2184 mL | 1.0918 mL | 2.1836 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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