1069-66-5 Usage
Uses
Used in Pharmaceutical Industry:
Sodium 2-propylpentanoate is used as an antiepileptic agent for increasing levels of GABA in the brain, which helps in controlling seizures and preventing epileptic episodes.
Used in Antimicrobial Applications:
In the healthcare industry, Sodium 2-propylpentanoate is used as an antibacterial agent, helping to combat bacterial infections and promote overall health.
Used in Neurological Applications:
Sodium 2-propylpentanoate is used as an anticonvulsant for treating various neurological disorders, such as epilepsy, by stabilizing the electrical activity in the brain and preventing seizures.
Used in Alzheimer's Disease Treatment:
Sodium 2-propylpentanoate is used as a therapeutic agent for Alzheimer's disease, as it has been shown to inhibit Aβ production, reduce neuritic plaque formation, and improve memory deficits in Alzheimer's mouse models.
Used in Stem Cell Research:
In the field of regenerative medicine, Sodium 2-propylpentanoate is used to improve stem cell reprogramming efficiency and enable efficient induction of pluripotency without the introduction of the oncogene c-Myc.
Chemical Properties:
Sodium 2-propylpentanoate is a white solid with the chemical formula ChEBI: The sodium salt of valproic acid.
Brand Name:
The brand name for Sodium 2-propylpentanoate is Depacon, manufactured by Abbott.
Originator
Anticon,Generics-UK,UK
Manufacturing Process
(a) Di-n-propyl cyanacetic acid
First of all, a sodium n-propylate solution was prepared from 7.42 g (0.322
mol) of sodium and 180 ml of anhydrous n-propanol, by heating with gentle
reflux until complete dissolution of the sodium.
Into a 500 ml spherical flask, equipped with a dropping funnel, a mechanical
stirrer, a thermometer and a condenser, above which was disposed a calcium
chloride trap, were introduced 16.95 g (0.141 mol) of ethyl cyanacetate and
40.69 g (0.33 mol) of n-propyl bromide. This mixture was heated to 45°C and
then there was added thereto, slowly and while stirring, the previously
prepared solution of sodium n-propylate, keeping the temperature of the
reaction medium at 50°-55°C by gentle external cooling.With the completion of the operation of introduction, the mixture was brought
to reflux temperature in 30 minutes and kept at this temperature for 3 hours.
The n-propanol was then distilled and the distillation stopped when the
temperature of the residual mass had reached 115°C.
The crude ester obtained in this way was then treated with a solution of 7.5 g
of flaked sodium hydroxide in 67.5 ml of water. The mixture was introduced
into a 250 ml spherical flask, equipped with a condenser, and then the
reaction medium was slowly brought to 60°-70°C. This temperature was
maintained for 3 hours, whereafter the mixture was cooled to about 50°C and
the ethanol which had formed and the residue of n-propanol were eliminated
under a pressure of 70 mm Hg. The solution thus obtained was cooled to
20°C and acidified, while stirring, by addition of 26.25 g of 36% hydrochloric
acid. During this operation, the temperature of the reaction medium was kept
below 40°C by cooling. Stirring was continued for 30 minutes, whereafter the
mixture was left standing for 30 minutes. The oily layer of di-n-propyl
cyanacetic acid was decanted and the aqueous phase extracted with 35 ml of
toluene. The extract in toluene was then added to the decanted di-n-propyl
cyanacetic acid, whereafter the solution in toluene was washed, in a
separation funnel, with a solution of 1.5 g of sodium chloride in 14 ml of
water. The toluenic phase was decanted and the toluene distilled under
atmospheric pressure.
Using this procedure, 25 g of crude di-n-propyl cyanacetic acid were obtained.
(b) Di-n-propyl acetonitrile
Into a 100 ml spherical flask fitted with a thermometer and a condenser were
introduced 25 g of crude di-n-propyl cyanacetic acid obtained by the method
previously described, and the mixture was heated on an oil bath.
Decarboxylation commenced at a temperature in the region of 140°C. The
mixture was refluxed at about 160°C and at 190°C for 2 hours. This
temperature was maintained until the release of gas was completed, this
taking 2 hours. The di-n-propyl acetonitrile thus formed was then slowly
distilled and the fraction passing over between 165°C and 175°C was
collected. A second distillation was then carried out. Using this procedure,
14.7 g of di-n-propyl acetonitrile were collected. Boiling point: 170°C. Yield:
83%, relatively to the ethyl cyanacetate used. Di-n-propyl acetonitrile may be
saponifyed with equal molecular quantity of NaOH to give the desired valproic
acid (valproate). After that it may be converted into the sodium salt with help
of equivalent NaOH to give the valproate sodium.
Therapeutic Function
Anticonvulsant, Antiepileptic
Biological Activity
Histone deacetylase inhibitor (IC 50 = 400 μ M) that exhibits anticancer, anti-inflammatory and neuroprotective effects. Displays anticonvulsive activity via an increase in GABA levels and decreases A β production in animal models of Alzheimer's disease. Also attenuates NMDA-mediated excitation, blocks voltage-gated Na + channels and modulates firing of neurons. Enables induction of pluripotent stem cells from somatic cells by Oct4 and Sox2.
Biochem/physiol Actions
Cell permeable: yes
Clinical Use
All forms of epilepsy
Migraine prophylaxis (unlicensed)
in vitro
vpa showed to have cellular neuroprotective properties. in cultured neurons, vpa protected from thapsigargin-induced endoplasmic reticulum stress, glutamate-induced excitotoxicity, as well as lipopolysaccharide (lps)-induced dopaminergic neuronal death. in midbrain neuron-glia cultures, vpa was also shown to inhibit lps-induced, microglia-mediated inflammation [1].
in vivo
post-pmcao injections with vpa could decrease the brain infarct volume. postinsult treatment with vpa also reduced the number of microglia, suppressed microglial activation, and inhibited other inflammatory markers in the ischemic brain. the reduction in acetylated histone h3 was prevented by treatment with vpa. moreover, vpa superinduced heat-shock protein 70 and blocked pmcao-induced down-regulation of cyclooxygenase-2. the sensory, motor, and reflex performance of pmcao rats was improved by vpa treatment [1].
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: metabolism possibly inhibited
by erythromycin; avoid with pivmecillinam;
concentration reduced by carbapenems - avoid.
Antidepressants: antagonise anticonvulsant effect;
avoid with St John’s wort.
Antiepileptics: concentration reduced by
carbamazepine; concentration of active carbamazepine
metabolite increased; increased concentration of
lamotrigine, phenobarbital, rufinamide and possibly
ethosuximide; sometimes reduces concentration of
active metabolite of oxcarbazepine; alters phenytoin
concentration; phenytoin and phenobarbital reduce
valproate concentration; hyperammonaemia and CNS
toxicity with topiramate.
Antimalarials: mefloquine antagonises
anticonvulsant effect.
Antipsychotics: antagonise anticonvulsant effect;
increased neutropenia with olanzapine; possibly
increases or decreases concentration of clozapine;
possibly increases quetiapine concentration.
Ciclosporin: variable ciclosporin blood level response.
Orlistat: possibly increased risk of convulsions.
Sodium oxybate: concentration of sodium oxybate
increased.
Ulcer-healing drugs: metabolism inhibited by
cimetidine, increased concentration.
IC 50
0.4 mm
Metabolism
Valproic acid is extensively metabolised in the liver, a large
part by glucuronidation (up to 60%) and the rest by a
variety of complex pathways (up to 45%).
It is excreted in the urine almost entirely in the form of
its metabolites; small amounts are excreted in faeces and
expired air.
References
1) Phiel et al. (2001), Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen; J. Biol. Chem. 276 36734
2) Kim et al. (2007), Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action; J. Pharmacol. Exp. Ther. 321 892
3) Qing et al. (2008), Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer’s mouse models; J. Exp. Med. 205 2781
4) Hangfu et al. (2008), Induction of pluripotent stem cells by defined factors is greatly improved by small molecule compounds; Nat. Biotechnol. 26 795
Check Digit Verification of cas no
The CAS Registry Mumber 1069-66-5 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,0,6 and 9 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1069-66:
(6*1)+(5*0)+(4*6)+(3*9)+(2*6)+(1*6)=75
75 % 10 = 5
So 1069-66-5 is a valid CAS Registry Number.
InChI:InChI=1/C8H16O2.Na/c1-3-5-7(6-4-2)8(9)10;/h7H,3-6H2,1-2H3,(H,9,10);/q;+1/p-1
1069-66-5Relevant articles and documents
Synthesis, characterization and behavior in water/DMSO solution of Ru(II) arene complexes with bioactive carboxylates
Biancalana, Lorenzo,Pampaloni, Guido,Zacchini, Stefano,Marchetti, Fabio
, p. 201 - 211 (2018)
The reactions of [RuCl(μ-Cl)(η6-p-cymene)]2 with sodium carboxylates, in methanol or acetonitrile solution, afforded the complexes [RuCl(κ2O-RCO2)(η6-p-cymene)] (RCO2 = valproate, 1; aspirinate, 2; diclofenate, 3), in 79–96% yields. Analogously, [RuCl(κ2O-dfCO2)(η6-benzene)], 4, was obtained in admixture with minor by-products from [RuCl(μ-Cl)(η6-benzene)]2 and sodium/silver diclofenate. The sequential reaction of [RuCl(μ-Cl)(η6-p-cymene)]2 with sodium salicylate and PPh3 gave [Ru(κ2O,O′-salCO2)(PPh3)(η6-p-cymene)], 5, in 70% yield. The hydride complex [Ru2Cl2(μ-Cl)(μ-H)(η6-p-cymene)2], 6, was produced in 36% yield from [RuCl(μ-Cl)(η6-p-cymene)]2 and sodium formate. An optimization of the experimental work-up allowed to isolate [RuCl(μ-Cl)(η6-p-cymene)]2 with an improved yield respect to the literature (98% vs. 65%). The bidentate coordination mode of the carboxylato ligands in 1–5 was unambiguously ascertained by IR and NMR spectroscopy, moreover the solid state structure of 1 was elucidated by single crystal X-ray diffraction. Complexes 1–3 experience rapid and quantitative dissociation of the carboxylato anion in DMSO/water/NaCl mixtures, mainly converting into [RuCl2(DMSO)(η6-p-cymene)], 7.
Preparation method of sodium valproate
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Paragraph 0044; 0050-0052; 0058-0060; 0066-0068; 0074; ..., (2021/08/06)
The invention discloses a preparation method of sodium valproate, which comprises the following steps of by taking 2-cyano-2-propyl valerate as a raw material and a sulfuric acid aqueous solution as a catalyst, obtaining a mixture of valproic acid and valproate at 120-160 DEG C, then hydrolyzing by using an alkali solution to obtain a valproate aqueous solution, and extracting, acidifying and rectifying to obtain valproic acid. The reaction yield can reach 76%, and the purity of valproic acid can reach 99%. Compared with the traditional mechanism of oxidizing amide into carboxylic acid by nitrous acid, the method provided by the invention avoids the pollution to the atmosphere and the water body caused by the conversion of sodium nitrite into nitrous acid in an acid environment and the further conversion of nitrous acid into nitric oxide and nitrogen dioxide gas under an acid condition, and improves the operation safety of operators at the same time; and corrosion of nitric oxide and nitrogen dioxide to equipment is avoided.
Pharmaceutical composition with high safety, and preparation method thereof
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Paragraph 0029-0040, (2021/06/22)
The invention provides a pharmaceutical composition with high safety, which is characterized in that the pharmaceutical composition contains not less than 90% of sodium valproate and not more than 0.014% of 2-methylvaleric acid; and the content of the sodium valproate is preferably not less than 95% and more preferably not less than 99%. Meanwhile, the invention also provides a preparation method and application of the pharmaceutical composition. The sodium valproate pharmaceutical composition and the preparation thereof in the invention provide an effective solution for improving the safety and the stability of the medicine. Meanwhile, the preparation method of the sodium valproate pharmaceutical composition disclosed by the invention is simple in process, high in yield, high in purity and suitable for industrial mass production.
Preparation method of sodium valproate
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Paragraph 0033; 0036-0037; 0038; 0041-0042; 0043; 0046-0047, (2020/07/14)
The invention provides a preparation method of sodium valproate, and belongs to the technical field of medicine synthesis. The method comprises the following steps: by taking ethyl valerate as a raw material, adding a methyl tert-butyl ether solution of a pyrrole metal reagent into an ether solution of ethyl valerate, then adding halopropane, carrying out an alkylation reaction, adding a weakly acidic solution in a dropwise manner to terminate the reaction after the reaction is finished, and washing with water to obtain an intermediate product; and adding a sodium hydroxide solution into the alcohol solvent of the intermediate product, carrying out a saponification reaction, and purifying to obtain sodium valproate after the saponification reaction is finished. The method is short in reaction route, high in total yield, easily available in raw materials, low in cost, high in operability and suitable for industrialization. The total molar yield of sodium valproate prepared by the methodis greater than or equal to 86.0%, and the purity of the final product is greater than or equal to 99.5%.
Vpa synthesis process (by machine translation)
-
Paragraph 0010, (2017/03/17)
The invention discloses a process for synthesizing valproic acid sodium, comprises the following processes: malonic acid diethyl ester and 1- the bromine is positive propane mutual dissolution, the mixture is slowly added at certain temperature ethanol solution of sodium ethylate, heating reflux 2 hours, to recycle ethanol 110 °C, cooling to 80 °C the following, add quantitative a water-soluble sodium bromide, added after laminating a fresh keeping 15-30% aqueous sodium hydroxide solution, for 60-70 °C hydrolysis 3 hours, the gas temperature of the temperature recovery ethanol 99 °C, cooling to 80 °C the following, and in adding hydrochloric acid and dyeworks, adding crude valproic acid dissolving dipropyl malonic acid, mixed acid forming the, mixed acid for 110-160 °C decarboxylation slowly increase and produce crudely valproic acid. Valproic acid crude product after being refined after rectification, to neutralize the sodium hydroxide aqueous solution, adding toluene reflux with water, dewatering and crystallization of the valproic acid sodium, filtering, chlorofrom washing drying to obtain the finished product. The process safety and environmental protection, good quality, low cost, is suitable for industrial production. (by machine translation)
METHOD FOR PREPARING METAL SALT OF VALPROIC ACID
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Page/Page column 2, (2011/04/14)
The present invention provides a simple, safe and more efficient process for preparing metal salts of valproic acid. The process includes steps of: (i) mixing valproic acid and a metal hydroxide (either dry solid or aqueous solution) in a drier to form a reaction mixture; and (ii) removing water, which is produced during the step of mixing the valproic acid and the metal hydroxide, from the reaction mixture to obtain the desired metal salts of valproic acid.
METHODS AND COMPOSITIONS FOR TREATING MOOD DISORDER
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Page/Page column 45, (2008/06/13)
The invention relates to compositions and methods for treating mood spectrum disorder. The compositions relate to novel combinations and formulations of pharmaceutical compounds for treatment of mood spectrum disorders. The methods provide for use of the compounds provided herein for the treatment of mood spectrum disorders in addition to the use of mood screens for diagnosing a patient.
Process for the preparation of substituted acetic acids and derivatives thereof
-
, (2008/06/13)
A process for the preparation of substituted acetic acids and derivatives thereof, having the formula STR1 wherein X is --COOH, --COOY or --CN, Y is --CH3 or --C2 H5, R1 is a saturated, branched or unbranched aliphatic radical having from 1 to 6 carbon atoms, a phenyl radical, or a phenyl radical substituted by alkyl or alkoxy groups, and R2 is hydrogen or a saturated, branched or unbranched aliphatic radical having from 1 to 6 carbon atoms, a phenyl radical, or a phenyl radical substituted by alkyl or alkoxy groups, wherein R1 and R2 may be the same or different which process comprises converting the corresponding malonic or cyanoacetic ester of the formula STR2 wherein Z is --COOY or --CN, and Y, R1 and R2 are identified as above at elevated temperature in the presence of a catalyst, e.g., a catalyst containing from about 50 to 75 weight percent SiO2 and from 15 to 19 weight percent Al2 O3 and exhibit ignition losses ranging from 15 to 20 weight percent.
