Brivaracetam
[CAS 357336-20-0]

Identification

• Classification: API >> Nervous system medication >> Brain metabolism regulating drug
• Name: Brivaracetam
• Synonyms: (alphaS,4R)-alpha-Ethyl-2-oxo-4-propyl-1-pyrrolidineacetamide; UCB-34714
• Molecular Formula: C₁₁H₂₀N₂O₂
• Molecular Weight: 212.29
• CAS Registry Number: 357336-20-0
• EC Number: 801-184-2
• SMILES: CCC[C@@H]1CC(=O)N(C1)[C@@H](CC)C(=O)N

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 409.3±28.0 °C 760 mmHg (Calc.)^*
• Flash point: 201.3±24.0 °C (Calc.)^*
• Solubility: DMSO: 10 mg /mL (Expl.)
• Index of refraction: 1.494 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H336
• Safety Statements: P261-P264-P270-P271-P301+P317-P304+P340-P319-P330-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302

chemBlink Chemical Story

Brivaracetam, CAS 357336-20-0, is an antiseizure medicine developed by UCB as a high-affinity ligand for synaptic vesicle protein 2A (SV2A). Its discovery is unusually instructive because the program grew directly from understanding the molecular target of an earlier drug, levetiracetam. Once SV2A was identified as levetiracetam's principal binding site, researchers could deliberately search for analogues with stronger and more selective binding.

UCB screened thousands of compounds related to the levetiracetam pharmacophore. Structure-activity studies showed that substitution at the 4-position of the pyrrolidone ring could increase SV2A affinity. The n-propyl analogue, later named brivaracetam, combined high affinity with strong antiseizure activity in animal models and was selected for development. Published studies report substantially higher SV2A affinity than levetiracetam.

SV2A is an integral synaptic-vesicle protein involved in neurotransmitter release, although the precise chain of events connecting ligand binding to seizure suppression is not completely resolved. FDA review documents describe brivaracetam as having high and selective affinity for brain SV2A and identify this interaction as the primary proposed mechanism for anticonvulsant activity.

The FDA approved brivaracetam in 2016 for treatment of partial-onset seizures, now generally termed focal-onset seizures. Chemically it remains close to levetiracetam: both contain a 2-pyrrolidone acetamide framework, but brivaracetam carries a propyl substituent and defined stereochemistry that markedly change target affinity and pharmacological behavior.

Brivaracetam is therefore a particularly clear example of target-guided drug optimization. Levetiracetam first revealed an unusual antiseizure phenotype; research then identified SV2A as its molecular target; medicinal chemists used that knowledge to search systematically for stronger ligands. Rather than discovering a completely unrelated scaffold, the program turned mechanistic understanding of one successful medicine into the design logic for the next.

References:
1. Rogawski MA. Brivaracetam: a rational drug discovery success story. Br J Pharmacol. 2008;154:1555-1557. PMID: 18552880.
2. Klitgaard H et al. Epilepsia. 2016;57:538-548. DOI: 10.1111/epi.13340.
3. Gillard M et al. Eur J Pharmacol. 2011;664:36-44. PMID: 21575627.
4. U.S. FDA, Brivaracetam NDA 205836/205837/205838, 2016.

Read more stories