| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Calcium channel
|
|---|---|
| ln Vitro |
Norverapamil ((±)-norverapamil) works well with verapamil to destroy intracellular tuberculosis branches and reduce isoniazid and rifampicin tolerance when no other medications are available. Bacilli produce a comparable result. In addition, norverapamil has comparable serum levels to verapamil and can prevent tolerance induced by macrophages [1]. The CYP3A mechanism-based inhibitors and substrates verapamil and its main metabolite norverapamil were found, and their nonlinear pharmacokinetics in the clinic were reported [3].
|
| ln Vivo |
Norverapamil (9 mg/kg; oral) is the main metabolite of verapamil, with terminal half-life, AUC, and Cmax values of 9.4 hours, 260 ng·h/ml, and 41.6 ng/mL, respectively [ 4].
|
| Cell Assay |
Drug tolerance likely represents an important barrier to tuberculosis treatment shortening. We previously implicated the Mycobacterium tuberculosis efflux pump Rv1258c as mediating macrophage-induced tolerance to rifampicin and intracellular growth. In this study, we infected the human macrophage-like cell line THP-1 with drug-sensitive and drug-resistant M. tuberculosis strains and found that tolerance developed to most antituberculosis drugs, including the newer agents moxifloxacin, PA-824, linezolid, and bedaquiline. Multiple efflux pump inhibitors in clinical use for other indications reversed tolerance to isoniazid and rifampicin and slowed intracellular growth. Moreover, verapamil reduced tolerance to bedaquiline and moxifloxacin. Verapamil's R isomer and its metabolite norverapamil have substantially less calcium channel blocking activity yet were similarly active as verapamil at inhibiting macrophage-induced drug tolerance. Our finding that verapamil inhibits intracellular M. tuberculosis growth and tolerance suggests its potential for treatment shortening. Norverapamil, R-verapamil, and potentially other derivatives present attractive alternatives that may have improved tolerability[1].
|
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [4]
Doses: 9 mg/kg (pharmacokinetic/PK/PK study) Route of Administration: Oral Experimental Results: t1/2=9.4 hrs (hrs (hours)); AUC=260 ng·h/ml; Cmax =41.6ng/ml. |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Norverapamil has known human metabolites that include 2-(3,4-dimethoxyphenyl)acetaldehyde, 5-Amino-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile, and D-715 (PR-22). Norverapamil is a known human metabolite of Verapamil. |
| References |
|
| Additional Infomation |
2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl]amino}-2-(propan-2-yl)pentanenitrile is a secondary amino compound that is 3,4-dimethoxyphenylethylamine in which one of the hydrogens attached to the nitrogen has been replaced by a 4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl group. It is an aromatic ether, a nitrile, a polyether and a secondary amino compound.
|
| Molecular Formula |
C26H36N2O4
|
|---|---|
| Molecular Weight |
440.575
|
| Exact Mass |
476.244
|
| Elemental Analysis |
C, 70.88; H, 8.24; N, 6.36; O, 14.53
|
| CAS # |
67018-85-3
|
| Related CAS # |
Norverapamil hydrochloride;67812-42-4;Norverapamil-d7 hydrochloride;1216413-74-9;Norverapamil-d7;263175-44-6
|
| PubChem CID |
104972
|
| Appearance |
Typically exists as solid at room temperature
|
| Boiling Point |
586.1ºC at 760 mmHg
|
| Flash Point |
308.2ºC
|
| LogP |
5.943
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
13
|
| Heavy Atom Count |
32
|
| Complexity |
577
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C)C1=C(C=CC(=C1)C(C#N)(CCCN([H])CCC1C=CC(=C(C=1)OC)OC)C(C)C)OC
|
| InChi Key |
UPKQNCPKPOLASS-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H36N2O4/c1-19(2)26(18-27,21-9-11-23(30-4)25(17-21)32-6)13-7-14-28-15-12-20-8-10-22(29-3)24(16-20)31-5/h8-11,16-17,19,28H,7,12-15H2,1-6H3
|
| Chemical Name |
2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile
|
| Synonyms |
NORVERAPAMIL (6%); CHEMBL1298; 2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-propan-2-ylpentanenitrile; 957Z3K3R56; 5-((3,4-dimethoxyphenethyl)amino)-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile; (+/-)-Norverapamil;D591;
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 2.2697 mL | 11.3487 mL | 22.6974 mL | |
| 5 mM | 0.4539 mL | 2.2697 mL | 4.5395 mL | |
| 10 mM | 0.2270 mL | 1.1349 mL | 2.2697 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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