Pregabalin

Base Information

• Chemical Name: Pregabalin
• CAS No.: 148553-50-8
• Molecular Formula: C8H17NO2
• Molecular Weight: 159.228
• Hs Code.: 29224999
• European Community (EC) Number: 604-639-1
• UNII: 55JG375S6M
• DSSTox Substance ID: DTXSID1045950
• Nikkaji Number: J702.547E
• Wikipedia: Pregabalin
• Wikidata: Q412174
• NCI Thesaurus Code: C64625
• RXCUI: 187832
• Pharos Ligand ID: 5FRSHFCBHS4X
• Metabolomics Workbench ID: 42632
• ChEMBL ID: CHEMBL1059
• Mol file: 148553-50-8.mol

Synonyms:(R-)-3-isobutyl GABA;(S)-3-(aminomethyl)-5-methylhexanoic acid;(S+)-3-isobutyl GABA;1008, CI;3 isobutyl GABA;3-(aminomethyl)-5-methylhexanoic acid;3-isobutyl GABA;CI 1008;CI-1008;CI1008;GABA, 3-isobutyl;Lyrica;pregabalin

Chemical Property of Pregabalin

Chemical Property:

• Appearance/Colour: off-white solid
• Vapor Pressure: 0.00153mmHg at 25°C
• Melting Point: 194-196 °C
• Refractive Index: 1.464
• Boiling Point: 274 °C at 760 mmHg
• PKA: 4.23±0.10(Predicted)
• Flash Point: 119.5 °C
• PSA: 63.32000
• Density: 0.997 g/cm³
• LogP: 1.78240
• Storage Temp.: Store at RT
• Solubility.: deionized water: ≥10mg/mL
• XLogP3: -1.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 5
• Exact Mass: 159.125928785
• Heavy Atom Count: 11
• Complexity: 123

Purity/Quality:

99.9% ^*data from raw suppliers

Pregabalin solution 1.0?mg/mL in methanol, ampule of 1?mL, certified reference material, Cerilliant? ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,T,F
• Hazard Codes: Xn,T,F
• Statements: 63-48/22-39/23/24/25-23/24/25-11
• Safety Statements: 22-36/37-45-16-7

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Anticonvulsants
• Canonical SMILES: CC(C)CC(CC(=O)O)CN
• Isomeric SMILES: CC(C)C[C@@H](CC(=O)O)CN
• Recent ClinicalTrials: Evaluation of Efficacy and Safety of VX-548 for Painful Diabetic Peripheral Neuropathy (DPN)
• Recent EU Clinical Trials: Combined effect of Pregabalin and Oxycodone, and Lacosamide and Oxycodone, on breathing: an exploratory study in healthy volunteers the POLO study
• Recent NIPH Clinical Trials: JORTC-PAL16
• Indications and Dosage: Pregabalin, marketed as Lyrica 庐, is classified as a gabapentinoid and primarily prescribed as an add-on drug for partial epileptic seizures. Additionally, it is indicated for neuropathic pain and generalized anxiety disorder (GAD) in adults, with dosages ranging from 300 to 600 mg per day.
• Off-Label Use: Despite lacking evidence of efficacy, pregabalin is increasingly prescribed off-label for conditions such as chronic low back pain or radicular pain.
• Prescription Trends: In Europe, pregabalin is prescribed to a small proportion of pregnant women, with usage increasing after 2010. It is commonly prescribed for neuropathic pain, followed by generalized anxiety disorder, and least frequently for epilepsy.
• Approved Indications: In different regions like Belgium, Sweden, and Serbia, pregabalin is approved for various indications including neuropathic pain, epilepsy (as adjunctive therapy), and generalized anxiety disorder
• Mechanism of Action: Pregabalin, a gamma-aminobutyric acid (GABA) analog, primarily acts as an anticonvulsant by inhibiting calcium channels, leading to a reduction in presynaptic neurotransmitter release and postsynaptic excitability. Its effects on central pain modulation have led to its approval for conditions like fibromyalgia.
• Effectiveness and Safety: Studies have investigated the effectiveness and safety of pregabalin, demonstrating its long-term safety and tolerability. Common adverse events include somnolence, dizziness, dry mouth, and peripheral edema, with the occurrence being dose-related.
• Clinical Trials: Double-blind, placebo-controlled randomized controlled trials (RCTs) have shown that the administration of pregabalin at doses of 300 mg/day resulted in a lower rate of adverse events.

Technology Process of Pregabalin

There total 272 articles about Pregabalin 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: 97.0%

5-methyl-3-(nitromethyl)hexanoic acid (181289-21-4) → (R,S)-3-iso-butyl-4-aminobutyric acid (128013-69-4,130912-52-6,148553-50-8,148553-51-9)

Guidance literature:

With palladium 10% on activated carbon; hydrogen; In methanol; at 25 ℃; for 24h; under 760.051 Torr;

DOI:10.1039/d0nj02263b

Reference yield: 95.0%

t-butyl 4-(2-methylpropyl)-2-oxopyrrolidine-1-carboxylate (1373869-02-3) → (R,S)-3-iso-butyl-4-aminobutyric acid (128013-69-4,130912-52-6,148553-50-8,148553-51-9)

Guidance literature:

t-butyl 4-(2-methylpropyl)-2-oxopyrrolidine-1-carboxylate; With sodium hydroxide; In methanol; for 1h; Reflux; Large scale;

With hydrogenchloride; In dichloromethane; water; at 20 ℃; for 0.5h; Large scale;

Reference yield: 89.0%

(±)?3?(carbamoylmethyl)?5?methylhexanoic acid (181289-15-6) → (R,S)-3-iso-butyl-4-aminobutyric acid (128013-69-4,130912-52-6,148553-50-8,148553-51-9)

Guidance literature:

With bromine; sodium hydroxide; In water; at 0 - 85 ℃; for 3h; Temperature; Large scale;

upstream raw materials:

3-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-5-methyl-hex-4-enoic acid ethyl ester

3-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-pent-4-enoic acid ethyl ester

4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-formyl-butyric acid ethyl ester

5-methyl-2-hexenoic acid ethyl ester

Downstream raw materials:

(S)-3-[N-(benzoyloxymethyleneoxycarbonyl)aminomethyl]-5-methylhexanoic acid

(S)-3-(benzoylaminomethyl)-5-methylhexanoic acid

C₈H₈O₃*C₈H₁₇NO₂

(S)-pregabalin-(-)-O,O'-dibenzoyl-L-tartrate

Refernces

• 1、 Chavan, Anil B.,Maikap, Golak C.,Gurjar, Mukund K.. "An efficient process of racemization of 3-(Carbamoylmethyl)-5- methylhexanoic acid: A pregabalin intermediate". . p. 812 - 814. Retrieved 2009.
• 2、 Winkler, Christoph K.,Clay, Dorina,Turrini, Nikolaus G.,Lechner, Horst,Kroutil, Wolfgang,Davies, Simon,Debarge, Sebastien,O'Neill, Pat,Steflik, Jeremy,Karmilowicz, Mike,Wong, John W.,Faber, Kurt. "Nitrile as activating group in the asymmetric bioreduction of β-cyanoacrylic acids catalyzed by ene-reductases". . p. 1878 - 1882. Retrieved 2014.
• 3、 Duan, Yitao,Yao, Peiyuan,Ren, Jie,Han, Chao,Li, Qian,Yuan, Jing,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming. "Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen". . p. 1164 - 1171. Retrieved 2014.
• 4、 Martinez, Carlos A.,Hu, Shanghui,Dumond, Yves,Tao, Junhua,Kelleher, Patrick,Tully, Liam. "Development of a chemoenzymatic manufacturing process for Pregabalin". . p. 392 - 398. Retrieved 2008.
• 5、 Izquierdo, Sandra,Aguilera, Jordi,Buschmann, Helmut H.,Garcia, Monica,Torrens, Antoni,Ortuno, Rosa M.. "Stereoselective and efficient synthesis of (S)-pregabalin from d-mannitol". . p. 651 - 653. Retrieved 2008.
• 6、 -. "PROCESS FOR THE PREPARATION OF GAMMA AMINO BUTYRIC ACIDS AND ANALOGS THEREOF". Page/Page column 14-15. . Retrieved 2021/08/20.