Ethosuximide

Base Information

• Chemical Name: Ethosuximide
• CAS No.: 77-67-8
• Molecular Formula: C7H11 N O2
• Molecular Weight: 141.17
• Hs Code.: 2925190100
• European Community (EC) Number: 201-048-7
• NSC Number: 758192,64013
• UNII: 5SEH9X1D1D
• DSSTox Substance ID: DTXSID7023019
• Nikkaji Number: J1.477J
• Wikipedia: Ethosuximide
• Wikidata: Q421567
• NCI Thesaurus Code: C47523
• RXCUI: 4135
• Pharos Ligand ID: VKRLPA37GDYW
• Metabolomics Workbench ID: 143454
• ChEMBL ID: CHEMBL696
• Mol file: 77-67-8.mol

Synonyms:Emeside;Ethosuccimid;Ethosuximide;Ethylmethylsuccimide;Ethymal;Etosuximida Faes;Faes, Etosuximida;Petnidan;Pyknolepsinum;Suksilep;Suxilep;Zarontin

Chemical Property of Ethosuximide

Chemical Property:

• Melting Point: 51 °C
• Refractive Index: 1.5026 (estimate)
• Boiling Point: 265.3 °C at 760 mmHg
• PKA: pKa 9.5 (Uncertain)
• Flash Point: 123.8 °C
• PSA: 46.17000
• Density: 1.1522 (rough estimate)
• LogP: 0.77800
• Storage Temp.: Refrigerator
• Solubility.: ethanol: 100 mg/mL
• Water Solubility.: 190g/L(25 oC)
• XLogP3: 0.4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 141.078978594
• Heavy Atom Count: 10
• Complexity: 188

Purity/Quality:

99% ^*data from raw suppliers

Ethosuximide ^*data from reagent suppliers

Safty Information:

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

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Anticonvulsants
• Canonical SMILES: CCC1(CC(=O)NC1=O)C
• Recent ClinicalTrials: Ethosuximide to Treat IBS
• Recent EU Clinical Trials: Evaluation of the effectiveness and safety of ethosuximide in the treatment of abdominal pain associated with irritable bowel syndrome
• Description: Ethosuximide is a first- generation antiepileptic drug (AED) known under the proprietary brand name of Zarontin? (Pfizer, New York, NY) in the UK and USA.
• Indications: Epilepsy: monotherapy and adjunctive therapy of absence seizures; adjunctive therapy of generalized tonic- clonic seizures. Recommendations summarized from NICE (2012) Seizure types: first line (absence seizures), adjunctive (absence seizures). Epilepsy types: first line (absence syndromes), adjunctive (absence syndromes).
• Uses: Ethosuximide is an anticonvulsant drug that is used in minor forms of epilepsy. cholinergic Anticonvulsant.
• Therapeutic Function: Anticonvulsant
• Biological Functions: It is now generally accepted that the specific antiepileptic action of ethosuximide (and the older agent trimethadione, no longer employed) against absence epilepsy is its ability to reduce the low-threshold calcium current (LTCC) or T (transient) current. These currents underlie the 3-Hz spike wave discharges that are characteristic of absence epilepsy. A blockade of T-calcium current is likely also to be a mechanism used by valproic acid. The only clinical use for ethosuximide (Zarontin) is in the treatment of absence epilepsy. If absence attacks are the only seizure disorder present, ethosuximide alone is effective. If other types of epilepsy are present, ethosuximide can be readily combined with other agents. For the most part, ethosuximide is a safe drug. Most of the side effects are dose related and consist of nausea, gastrointestinal irritation, drowsiness, and anorexia. A variety of blood dyscrasias have been reported, but serious blood disorders are quite rare.
• Clinical Use: Although ethosuximide is the drug of choice for treatment of simple absence seizures, it is not effective against partial complex or tonic-clonic seizures and may increase the frequency of grand mal attacks. Thus, it must be administered in combination with other AEDs when treating persons with mixed seizure types. Ethosuximide is a substrate for both CYP3A4 and CYP2E1. The major metabolite for ethosuximide is 3-(1-hydroxyethyl) succinimide, which is inactive and excreted unconjugated into the urine Several additional metabolites have been characterized recently. Approximately 20% of an oral dose is excreted unchanged. Although ethosuximide is thought to be the least toxic of the succinimides, it can cause gastrointestinal disturbances and dose-related CNS effects, such as drowsiness, dizziness, ataxia, sleep disturbances and depression. Idiosyncratic hypersensitivity reactions include severe rashes, leukopenia, agranulocytosis (some fatal), systemic lupus erythematosus, and parkinsonian-like symptoms. In addition to being less toxic than trimethadione, ethosuximide offers a wider range of protection against different kinds of absence seizures.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration increased by isoniazid. Antidepressants: lower convulsive threshold; avoid with St John’s wort. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenytoin and phenobarbital; concentration of fosphenytoin and phenytoin possibly increased; concentration increased by valproate. Antimalarials: anticonvulsant effect antagonised by mefloquine. Antipsychotics: lower convulsive threshold. Orlistat: possible increased risk of convulsions.

Technology Process of Ethosuximide

There total 11 articles about Ethosuximide 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: 83.0%

C14H17NO3 → ethosuximide (77-67-8)

Guidance literature:

C₁₄H₁₇NO₃; With palladium on activated charcoal; hydrogen;

With triethylamine; α-bromoacetophenone;

DOI:10.1039/c9sc03175h

Reference yield: 47.0%

4-ethyl-1-(4-methoxybenzyl)-4-methylpyrrolidine-2,5-dione (166324-36-3) → ethosuximide (77-67-8)

Guidance literature:

With ammonium cerium(IV) nitrate; In water; acetonitrile; for 1h; Ambient temperature;

DOI:10.1016/0040-4020(95)00056-E

Reference yield:

2-ethyl-2-methylsuccinic acid (631-31-2) → ethosuximide (77-67-8)

Guidance literature:

With ammonia;

DOI:10.1021/jo00326a031

upstream raw materials:

2-ethyl-2-methylsuccinic acid

4-ethyl-1-(4-methoxybenzyl)-4-methylpyrrolidine-2,5-dione

2-Methylbutyraldehyde

4-ethyl-5-hydroxy-1-(4-methoxybenzyl)-4-methylpyrrolidin-2-one

Downstream raw materials:

3-methyl-3-ethyl-1-{[(4-methylphenyl)amino]methyl}pyrrolidine-2,5-dione

3-ethyl-1,3-dimethyl-2,5-pyrrolidinedione

N-[{4-(3,4-dichlorophenyl)-piperazin-1-yl}-methyl]-3-ethyl-3-methyl-pyrrolidine-2,5-dione

N-[{4-(4-chlorophenyl)-piperazin-1-yl}-methyl]-3-ethyl-3-methyl-pyrrolidine-2,5-dione

Refernces

• 1、 -. "AMIDOALKYLPIPERAZINYL DERIVATIVES FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES". Page/Page column 28; 29. . Retrieved 2013/03/26.
• 2、 Ishibashi, Hiroyuki,Nakaharu, Tohru,Nishimura, Masako,Nishikawa, Atsuko,Kameoka, Chisato,Ikeda, Masazumi. "Uncatalyzed Cationic Olefin Cyclizations of N-Vinylic α-Chloro-α-thioacetamides. Formation of β- and γ-Lactams". . p. 2929 - 2938. Retrieved 2007/10/02.