Levetiracetam

Base Information

• Chemical Name: Levetiracetam
• CAS No.: 102767-28-2
• Molecular Formula: C8H14N2O2
• Molecular Weight: 170.211
• Hs Code.: 2933990090
• European Community (EC) Number: 600-348-9
• NSC Number: 760119
• UNII: 44YRR34555
• DSSTox Substance ID: DTXSID9023207
• Nikkaji Number: J523.599E
• Wikipedia: Levetiracetam
• Wikidata: Q417227
• NCI Thesaurus Code: C47581
• RXCUI: 114477
• Pharos Ligand ID: 1D981BVUG2F4
• Metabolomics Workbench ID: 53254
• ChEMBL ID: CHEMBL1286
• Mol file: 102767-28-2.mol

Synonyms:alpha ethyl 2 oxo 1 Pyrrolidineacetamide;alpha-ethyl-2-oxo-1-pyrrolidineacetamide;etiracetam;Etiracetam, (R)-;Etiracetam, R isomer;etiracetam, R-isomer;Etiracetam, S isomer;etiracetam, S-isomer;Keppra;levetiracetam;R-isomer Etiracetam;S-isomer Etiracetam;UCB 6474;ucb L059;ucb L060;UCB-6474;ucb-L059;ucb-L060;UCB6474;UcbL060

Chemical Property of Levetiracetam

Chemical Property:

• Appearance/Colour: White crystalline powder
• Vapor Pressure: 1.78E-06mmHg at 25°C
• Melting Point: 118-119 °C
• Refractive Index: 1.518
• Boiling Point: 395.9 °C at 760 mmHg
• Flash Point: 193.2 °C
• PSA: 63.40000
• Density: 1.168 g/cm³
• LogP: 0.51090
• XLogP3: -0.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 170.105527694
• Heavy Atom Count: 12
• Complexity: 203

Purity/Quality:

99% ^*data from raw suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Anticonvulsants
• Canonical SMILES: CCC(C(=O)N)N1CCCC1=O
• Isomeric SMILES: CC[C@@H](C(=O)N)N1CCCC1=O
• Recent ClinicalTrials: Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia
• Recent EU Clinical Trials: “FAST ACUTE SEDATION AT INTENSIVE CARE VS. HIGH-DOSE I.V. ANTI-SEIZURE MEDICATION FOR TREATMENT OF NON-CONVULSIVE STATUS EPILEPTICUS - A RANDOMIZED, MULTICENTER TRIAL (FAST TRIAL)”
• Recent NIPH Clinical Trials: Levetiracetam pharmacokinetics analysis and elucidation of appropriate administration design in critically ill patients
• Uses: Approximately 50 million people worldwide are affected by epilepsy. ^[3] Levetiracetam was approved by the US FDA in November 1999 as add-on therapy for the treatment of partial-onset seizures in adults (age 16 years and older). Levetiracetam is a Pregnancy Category C drug. Overall, when used in combination with other AEDs, levetiracetam was generally well tolerated as add-on treatment for partial-onset seizures.^[1]; Levetiracetam (LEV) stands out from other AEDs due to its novel and main mechanism of action through the interaction with the synaptic vesicle protein 2A (SV2A) ^[3].
• Pharmacokinetics: Pharmacokinetic studies of levetiracetam have been conducted in healthy volunteers, in adults, children and elderly patients with epilepsy, and in patients with renal and hepatic impairment. After oral ingestion, levetiracetam is rapidly absorbed, with peak concentration occurring after 1.3 hours, and its bioavailability is ≥95%. Co-ingestion of food slows the rate but not the extent of absorption. Levetiracetam is not bound to plasma proteins and has a volume of distribution of 00.5–0.7 L/kg. Plasma concentrations increase in proportion to dose over the clinically relevant dose range (500–5000mg) and there is no evidence of accumulation during multiple administration. Steady-state blood concentrations are achieved within 24–48 hours.; The elimination half-life in adult volunteers, adults with epilepsy, children with epilepsy and elderly volunteers is 6–8, 6–8, 5–7 and 10–11 hours, respectively. Approximately 34% of a levetiracetam dose is metabolised and 66% is excreted in urine unmetabolised; however, the metabolism is not hepatic but occurs primarily in blood by hydrolysis. Autoinduction is not a feature. As clearance is renal in nature it is directly dependent on creatinine clearance. Consequently, dosage adjustments are necessary for patients with moderate to severe renal impairment.^[2]
• Potential and Exploration: A vast number of studies have reported many other molecular targets, besides the SV2A protein, through which LEV can exert its action directly or indirectly. Additionally, important evidence has shown that LEV has anti-ictogenic, antiepileptogenic, neuroprotective, anti-inflammatory, and antioxidant effects. Recently, LEV has been catalogued as a multitarget drug with interesting properties that are able to address some of the current necessities in epilepsy and in other conditions. ^[3]
• Regulatory Status: Levetiracetam (LEV) was approved in the early 2000s as an antiepileptic drug in both the United States and the European Union, rapidly reaching the 200,000 patient-year usage milestone by the end of 2002.^[3]
• References: [1] Safety Profile of Levetiracetam (DOI 10.1111/j.1528-1167.2001.00008.x); [2] Clinical Pharmacokinetics of Levetiracetam (DOI 10.2165/00003088-200443110-00002); [3] Levetiracetam Mechanisms of Action: From Molecules to Systems (DOI 10.3390/ph15040475)

Technology Process of Levetiracetam

There total 63 articles about Levetiracetam 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: 99.9%

dehydro levetiracetam → levetiracetam (102767-28-2)

Guidance literature:

With C₆₈H₇₂Cl₂Co₂P₄; hydrogen; In methanol; at 50 ℃; Reagent/catalyst; enantioselective reaction;

DOI:10.1126/science.aar6117

Reference yield: 93.7%

2-pyrrolidinon (616-45-5) + 2-chlorobutyramide (7462-73-9) → levetiracetam (102767-28-2)

Guidance literature:

2-pyrrolidinon; With sodium hydroxide; In toluene; at 20 ℃; for 1.5h;

2-chlorobutyramide; With C₃₈H₃₃O₈P; In toluene; for 14h; Reagent/catalyst; Time; Reflux;

Reference yield: 91.2%

2-pyrrolidinon (616-45-5) + 2-bromobutyramide (5398-24-3) → levetiracetam (102767-28-2)

Guidance literature:

2-pyrrolidinon; With sodium hydroxide; In toluene; at 20 ℃; for 1.5h;

2-bromobutyramide; With C₃₈H₃₃O₈P; In toluene; for 16h; Reflux;

upstream raw materials:

α-ethyl-2-oxo-1-pyrrolidineacetic acid,

(R)-2-pyrrolidone-N-butyric acid

(2S)-2-(2-oxopyrrolidin-1-yl)butanoic acid

(S)-methyl 2-(2-oxopyrrolidin-1-yl)-2-butanoate

Downstream raw materials:

α-ethyl-2-oxo-1-pyrrolidineacetamide

C₈H₈O₃*C₈H₁₄N₂O₂

(S)-2-(4-fluorophenyl)-2-hydroxyacetic acid

(R)-2-(4-bromophenyl)-2-hydroxyacetic acid

Refernces

• 1、 Cioc, R?zvan C.,Schaepkens van Riempst, Lola,Schuckman, Peter,Ruijter, Eelco,Orru, Romano V. A.. "Ugi Four-Center Three-Component Reaction as a Direct Approach to Racetams". . p. 1664 - 1674. Retrieved 2017.
• 2、 Song, Lixing,Shemchuk, Oleksii,Robeyns, Koen,Braga, Dario,Grepioni, Fabrizia,Leyssens, Tom. "Ionic Cocrystals of Etiracetam and Levetiracetam: The Importance of Chirality for Ionic Cocrystals". . p. 2446 - 2454. Retrieved 2019.
• 3、 Arndt, Sebastian,Grill, Birgit,Schwab, Helmut,Steinkellner, Georg,Pogorev?nik, Ur?ka,Weis, Dominik,Nauth, Alexander M.,Gruber, Karl,Opatz, Till,Donsbach, Kai,Waldvogel, Siegfried R.,Winkler, Margit. "The sustainable synthesis of levetiracetam by an enzymatic dynamic kinetic resolution and an: Ex-cell anodic oxidation". . p. 388 - 395. Retrieved 2021.
• 4、 Springuel, Geraldine,Collard, Laurent,Leyssens, Tom. "Ternary and quaternary phase diagrams: Key tools for chiral resolution through solution cocrystallization". . p. 7951 - 7958. Retrieved 2013.
• 5、 Li, Zhen,Wu, Chengjun,Liu, Jiazu,Li, Linwei,Sun, Changshan,Sun, Tiemin. "Theoretical studies on racemization of levetiracetam: Structural movements, character of hydroxide ion and guidelines for efficient control". . . Retrieved 2019.
• 6、 Kotkar, Shriram P.,Sudalai, Arumugam. "A short enantioselective synthesis of the antiepileptic agent, levetiracetam based on proline-catalyzed asymmetric α-aminooxylation". . p. 6813 - 6815. Retrieved 2006.
• 7、 -. "Preparation method of levetiracetam". Paragraph 0026-0050. . Retrieved 2021/10/20.