Gabapentin enacarbil

Base Information

• Chemical Name: Gabapentin enacarbil
• CAS No.: 478296-72-9
• Deprecated CAS: 791632-57-0
• Molecular Formula: C16H27NO6
• Molecular Weight: 329.393
• UNII: 75OCL1SPBQ
• DSSTox Substance ID: DTXSID30870359
• Nikkaji Number: J3.209.908D
• Wikipedia: Gabapentin_enacarbil
• Wikidata: Q5515257
• NCI Thesaurus Code: C79579
• RXCUI: 1101333
• Pharos Ligand ID: 81W8SQNQMY9A
• Metabolomics Workbench ID: 65192
• ChEMBL ID: CHEMBL1628502
• Mol file: 478296-72-9.mol

Synonyms:1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid;gabapentin enacarbil;XP 10569;XP 11084;XP 11239;XP 12464;XP 13512;XP-10569;XP-11084;XP-11239;XP-12464;XP-13512;XP10569;XP11084;XP11239;XP12464;XP13512

Chemical Property of Gabapentin enacarbil

Chemical Property:

• Melting Point: 65 °C
• Boiling Point: 482.021 °C at 760 mmHg
• Flash Point: 245.318 °C
• PSA: 101.93000
• Density: 1.135 g/cm³
• LogP: 3.07390
• XLogP3: 3.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 9
• Exact Mass: 329.18383758
• Heavy Atom Count: 23
• Complexity: 428

Purity/Quality:

98%,99%, ^*data from raw suppliers

Gabapentinenacarbil ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)C(=O)OC(C)OC(=O)NCC1(CCCCC1)CC(=O)O
• Recent ClinicalTrials: Nighttime Agitation and Restless Legs Syndrome in People With Alzheimer's Disease
• Recent EU Clinical Trials: Response to gabapentin enacarbil in two groups of RLS patients: Previously exposed to long-term treatment with dopaminergic agents versus dopaminergic treatment-naive patients.
• Description: Gabapentin enacarbil (GEn) is an actively transported prodrug of gabapentin that provides sustained doseproportional exposure to gabapentin and predictable bioavailability. In April 2011, Gabapentin enacarbil is approved by the US Food and Drug Administration for the treatment of moderate-to-severe primary restless legssyndrome (RLS) in adults.Gabapentin enacarbil was designed to be recognized as a substrate for two high-capacity nutrient transports, monocarboxylate transporter type 1 and sodium-dependent multivitamin transporter, and to be efficiently cleaved after absorption to give gabapentin. The separated enantiomers of gabapentin enacarbil have similar cleavage rates in human tissues. Preclinical studies showed that gabapentin enacarbil provides good systemic exposure of gabapentin in rats and monkeys.
• Uses: Gabapentin enacarbil (HORIZANT GlaxoSmithKline/XenoPort) is a prodrug of gabapentin used as an anticonvulsant as well as a treatment for neurogenic pain, with the same mechanism of action as pregabalin.
• Clinical Use: Gabapentin enacarbil is a prodrug of gabapentin (Neurontin, Pfizer) which binds to the a2-d subunit of L-type voltage-regulated calcium channels, reducing the release of several neurotransmitters. 122,123 Gabapentin enacarbil was discovered at XenoPort, codeveloped with GlaxoSmithKline, is marketed under the brand name Horizant, and is approved for the treatment of moderate to severe restless leg syndrome. Gabapentin enacarbil was designed to increase the absorption of gabapentin through the interaction with sodium-dependent multivitamin transporter (SMVT) and monocarboxylate transporter type 1 (MCT-1). As a result, the drug demonstrated much better oral bioavailability and more consistent exposure compared to the parent.

Technology Process of Gabapentin enacarbil

There total 25 articles about Gabapentin enacarbil 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: 100.0%

H-Gpn-OH (60142-96-3) + 1-[[(4-nitrophenoxy)carbonyl]oxy]-2-methylpropionic acid ethyl ester (194995-47-6) → gabapentin enacarbil (478296-72-9)

Guidance literature:

With chloro-trimethyl-silane; tributyl-amine; In toluene; at 20 ℃; for 24h; Product distribution / selectivity;

Reference yield: 100.0%

[(1-isobutanoyloxyethoxy)carbonyloxy]succinimide + H-Gpn-OH (60142-96-3) → gabapentin enacarbil (478296-72-9)

Guidance literature:

In water; acetonitrile; at 20 ℃; for 3.5h; Product distribution / selectivity;

Reference yield: 99.5%

1-[[[(2,5-dioxopyrrolidin-1-yl)oxy]carbonyl]oxy]ethyl 2-methylpropanoate (860035-10-5) + H-Gpn-OH (60142-96-3) → gabapentin enacarbil (478296-72-9)

Guidance literature:

In tert-butyl methyl ether; water; at 20 ℃; for 7.5h; Product distribution / selectivity;

upstream raw materials:

1-{[(α-chloroethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid

isobutyric Acid

C₁₅H₂₈ClNO₄Si

H-Gpn-OH

Refernces

• 1、 -. "METHOD OF MAKING 1-(ACYLOXY)-ALKYL CARBAMATE COMPOUNDS". Paragraph 0291-0293. . Retrieved 2014/09/03.
• 2、 -. "PROCESSES FOR PREPARING PRODRUGS OF GABAPENTIN AND INTERMEDIATES THEREOF". Page/Page column 8. . Retrieved 2009/12/28.