Valproic Acid

Base Information

• Chemical Name: Valproic Acid
• CAS No.: 99-66-1
• Molecular Formula: C8H16O2
• Molecular Weight: 144.214
• Hs Code.: 29159080
• European Community (EC) Number: 202-777-3
• NSC Number: 93819
• UNII: 614OI1Z5WI
• DSSTox Substance ID: DTXSID6023733
• Nikkaji Number: J4.972G
• Wikipedia: Valproate
• Wikidata: Q240642
• NCI Thesaurus Code: C29536
• RXCUI: 11118
• Pharos Ligand ID: F3BQDP62S1D8
• Metabolomics Workbench ID: 337
• ChEMBL ID: CHEMBL109
• Mol file: 99-66-1.mol

Synonyms:2 Propylpentanoic Acid;2-Propylpentanoic Acid;Calcium Valproate;Convulsofin;Depakene;Depakine;Depakote;Dipropyl Acetate;Divalproex;Divalproex Sodium;Ergenyl;Magnesium Valproate;Propylisopropylacetic Acid;Semisodium Valproate;Sodium Valproate;Valproate;Valproate Calcium;Valproate Sodium;Valproic Acid;Valproic Acid, Sodium Salt (2:1);Vupral

Chemical Property of Valproic Acid

Chemical Property:

• Appearance/Colour: Colorless liquid
• Vapor Pressure: 1.39E-22mmHg at 25°C
• Melting Point: 120 - 130oC
• Refractive Index: 1.4250
• Boiling Point: 220 °C at 760 mmHg
• PKA: 4.6(at 25℃)
• Flash Point: 116.6 °C
• PSA: 37.30000
• Density: 0.926 g/cm³
• LogP: 2.28740
• Storage Temp.: 2-8°C
• Solubility.: H2O: slightly soluble
• Water Solubility.: slightly soluble
• XLogP3: 2.8
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 5
• Exact Mass: 144.115029749
• Heavy Atom Count: 10
• Complexity: 93.4

Purity/Quality:

98% ^*data from raw suppliers

Valproic acid ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,T,F
• Hazard Codes: Xn,T,F
• Statements: 22-36/37/38-39/23/24/25-23/24/25-11-34-61
• Safety Statements: 26-45-36/37-16-7-36/37/39-53

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CCCC(CCC)C(=O)O
• Recent ClinicalTrials: Valproic Acid/Simvastatin Plus Gemcitabine/Nab-paclitaxel Based Regimens in Untreated Metastatic Pancreatic Adenocarcinoma Patients
• Recent EU Clinical Trials: Randomized phase 2 study of Valproic acid combinEd with Simvastatin and gemcitabine/nab-paclitaxel-based regimens in untreated metastatic Pancreatic Adenocarcinoma patients (The VESPA trial)
• Recent NIPH Clinical Trials: Efficacy and safety of valproic acid in patients with postviral olfactory dysfunction
• Description: Valproate is a first- generation antiepileptic drug (AED) known with the proprietary brand names of Epilim? (Sanofi, Paris) and Episenta? (Desitin, Hamburg) in the UK and Depakote? (Sanofi, Paris) in the USA. Valproic acid and its salts are a new group of antiepileptic drugs that differs from the known drugs both structurally and in terms of its mechanism of action. It is believed that it acts on the metabolism of the GABA system. Valproic acid has been shown to elevate the level of GABA in the brain by means of competitive inhibition of GABA transaminase and the dehydrogenase of succinic semialdehyde. This drug not only exhibits anticonvulsant action, but also betters the mental condition of the patient.
• Indications: Epilepsy Monotherapy and adjunctive therapy of focal and generalized seizures. Recommendations summarized from NICE (2012) Seizure types: first line (generalized tonic- clonic seizures, tonic/ atonic seizures, absence seizures, myoclonic seizures, focal seizures), adjunctive (generalized tonic- clonic seizures, absence seizures, myoclonic seizures, focal seizures). Epilepsy types: first line (absence syndromes, juvenile myoclonic epilepsy, epilepsy with generalized tonic- clonic seizures only, idiopathic generalized epilepsy, benign epilepsy with centrotemporal spikes, Panayiotopoulos syndrome, late- onset childhood occipital epilepsy, Dravet syndrome, Lennox– Gastaut syndrome), adjunctive (absence syndromes, juvenile myoclonic epilepsy, epilepsy with generalized tonic- clonic seizures only, idiopathic generalized epilepsy, benign epilepsy with centrotemporal spikes, panayiotopoulos syndrome, late- onset childhood occipital epilepsy). Psychiatry Treatment of acute mania associated with bipolar disorder. Neurology Migraine prophylaxis (unlicensed).
• Uses: For treatment and management of seizure disorders, mania, and prophylactic treatment of migraine headache. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures asso 2-Propylpentanoic acid has been used as a supplement in mouse embryonic fibroblast - conditioned medium (MEF-CM)?to feed the cells.
• Therapeutic Function: Anticonvulsant
• Biological Functions: Although it is marketed as both valproic acid (Depakene) and as sodium valproate (Depakote), it is the valproate ion that is absorbed from the gastrointestinal tract and is the active form. As with several other AEDs, it is difficult to ascribe a single mechanism of action to valproic acid.This compound has broad anticonvulsant activity, both in experimental studies and in the therapeutic management of human epilepsy.Valproic acid has been shown to block voltage-dependent sodium channels at therapeutically relevant concentrations. In several experimental studies, valproate caused an increase in brain GABA; the mechanism was unclear.There is evidence that valproate may also inhibit T-calcium channels and that this may be important in its mechanism of action in patients with absence epilepsy.
• Clinical Use: Valproic acid is well absorbed from the gastrointestinal tract and is highly bound (~90%) to plasma protein, and most of the compound is therefore retained within the vascular compartment.Valproate rapidly enters the brain from the circulation; the subsequent decline in brain concentration parallels that in plasma, indicating equilibration between brain and capillary blood. A large number of metabolites have been identified, but it is not known whether they play a role in the anticonvulsant effect of the parent drug. Valproic acid inhibits the metabolism of several drugs, including phenobarbital, primidone, carbamazepine, and phenytoin, leading to an increased blood level of these compounds. At high doses, valproic acid can inhibit its own metabolism. It can also displace phenytoin from binding sites on plasma proteins, with a resultant increase in unbound phenytoin and increased phenytoin toxicity. In this instance, the dosage of phenytoin should be adjusted as required. These examples reinforce the need to determine serum anticonvulsant levels in epileptic patients when polytherapy is employed. Valproic acid has become a major AED against several seizure types. It is highly effective against absence seizures and myoclonic seizures. In addition, valproic acid can be used either alone or in combination with other drugs for the treatment of generalized tonic– clonic epilepsy and for partial seizures with complex symptoms.

Technology Process of Valproic Acid

There total 51 articles about Valproic Acid which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.0%

valproic acid calcium salt (33433-82-8,98378-05-3,119923-11-4) → valproic acid (99-66-1)

Guidance literature:

With hydrogenchloride; In water;

Reference yield: 98.0%

magnesium valproate → valproic acid (99-66-1)

Guidance literature:

With hydrogenchloride; In water;

Reference yield: 97.7%

di-n-propylmalonic acid (1636-27-7) → valproic acid (99-66-1)

Guidance literature:

copper(I) oxide; In acetonitrile; at 90 - 100 ℃; for 12 - 15h; Product distribution / selectivity;

upstream raw materials:

methyl magnesium iodide

2,2-dipropyl-malonic acid diethyl ester

ethyl 2-acetyl-2-propylpentanoate

2-propylpentanal

Downstream raw materials:

ethyl 2-propylpentanoate

valproyl chloride

2-bromo-2-propyl pentanoic acid ethyl ester

1-(4-methoxy-phenyl)-2-propyl-pentan-1-one

Refernces

• 1、 Palmieri, Alessandro,Gabrielli, Serena,Ballini, Roberto. "Michael reaction of nitroalkanes with β-nitroacrylates under a solid promoter: Advanced regio-and diastereoselective synthesis of nitro-functionalized ββ-unsaturated esters and 1,3-butadiene-2-carboxylates". . p. 1485 - 1492. Retrieved 2010.
• 2、 -. "Novel method for preparing valproic acid". Paragraph 0018; 0027-0051. . Retrieved 2021/08/06.
• 3、 -. "Method for recovering 2-propylmalonic acid and preparing valproic acid from 2-propylmalonic acid". Paragraph 0015-0030. . Retrieved 2021/01/15.