Tiagabine

Base Information

• Chemical Name: Tiagabine
• CAS No.: 115103-54-3
• Molecular Formula: C20H25NO2S2
• Molecular Weight: 375.556
• UNII: Z80I64HMNP
• DSSTox Substance ID: DTXSID5023663
• Nikkaji Number: J390.632I
• Wikipedia: Tiagabine
• Wikidata: Q907219
• NCI Thesaurus Code: C66602
• RXCUI: 31914
• Pharos Ligand ID: KWXTL21QA8XP
• Metabolomics Workbench ID: 43175
• ChEMBL ID: CHEMBL1027
• Mol file: 115103-54-3.mol

Synonyms:(R)-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)-3-piperidinecarboxylic acid, hydrochloride;Gabitril;N-(4,4-di(3-methylthien-2-yl)but-3-enyl)nipecotic acid;NO 328;NO 329;NO-328;NO-329;tiagabine;Tiagabine Hydrochloride;tiagabine, (S)-isomer

Chemical Property of Tiagabine

Chemical Property:

• Appearance/Colour: white to off-white crystalline solid
• Vapor Pressure: 9.71E-14mmHg at 25°C
• Melting Point: 192 °C
• Refractive Index: 1.604
• Boiling Point: 568 °C at 760 mmHg
• PKA: 3.86±0.20(Predicted)
• Flash Point: 297.3 °C
• PSA: 97.02000
• Density: 1.208 g/cm³
• LogP: 5.78470
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• XLogP3: 2.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 375.13267139
• Heavy Atom Count: 25
• Complexity: 474

Purity/Quality:

99.5% ^*data from raw suppliers

Tiagabine-d4HCl ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-37/39

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Anticonvulsants
• Canonical SMILES: CC1=C(SC=C1)C(=CCCN2CCCC(C2)C(=O)O)C3=C(C=CS3)C
• Isomeric SMILES: CC1=C(SC=C1)C(=CCCN2CCC[C@H](C2)C(=O)O)C3=C(C=CS3)C
• Recent ClinicalTrials: Evaluate the Safety of GABITRIL in Adults With Generalized Anxiety Disorder
• Recent EU Clinical Trials: THE IMPACT OF REDUCING OVERTREATMENT ON QUALITY OF LIFE IN CHILDREN
• Description: Tiagabine is a second- generation antiepileptic drug (AED) known under the proprietary brand name of Gabitril? (Teva, Petah Tikva, Israel) in the UK and USA. Gabitril was launched in Denmark for use as an add-on therapy in patients refractory to other epilepsy therapies. The compound can be synthesized in five steps beginning with a bis-thiophenyl ketone derivative to produce the (R)-(-)- enantiomer. Its anti-epileptic activity resides in its potent and selective inhibition of GABA synaptosomal uptake. Tiagabine is selective for the GAT-1 GABA transporter in neurons and glia thus enhancing inhibitory GABAergic transmission. Because it has practically no effect on other uptake or receptor systems, it has a reduced potential for neurological side-effects. In particular, it does not have the benzodiazepine-like sedative effects. It is able to cross the blood brain barrier and is considered the most potent GABA uptake inhibitor known.
• Indications: Epilepsy: adjunctive therapy for focal seizures with or without secondary generalization that are not satisfactorily controlled by other AEDs. Recommendations summarized from NICE (2012) Seizure types: on referral to tertiary care (focal seizures), contraindicated (generalized tonic- clonic seizures, tonic/ atonic seizures, absence seizures, myoclonic seizures). Epilepsy types: on referral to tertiary care (benign epilepsy with centrotemporal spikes, panayiotopoulos syndrome, late- onset childhood occipital epilepsy), contraindicated (absence syndromes, idiopathic generalized epilepsy, juvenile myoclonic epilepsy, Dravet syndrome, Lennox– Gastaut syndrome).
• Uses: A GABA uptake inhibitor
• Therapeutic Function: Antiepileptic
• Biological Functions: Tiagabine (Gabitril) blocks the reuptake of GABA into neurons and glia, thereby resulting in higher levels of GABA in the synaptic cleft. The ability to increase GABA concentrations is presumed to be involved in the effectiveness of tiagabine in the treatment of seizure disorders. It is primarily used in the treatment of partial complex seizures.Adverse effects of tiagabine administration include dizziness, somnolence, nervousness, nausea, and confusion.
• Clinical Use: Antiepileptic
• Drug interactions: Potentially hazardous interactions with other drugs Antidepressants: antagonism of anticonvulsant effect with SSRIs, tricyclics and MAOIs (convulsive threshold lowered); avoid with St John’s wort. Antiepileptics: concentration reduced by phenytoin, carbamazepine and phenobarbital. Antimalarials: mefloquine antagonises anticonvulsant. Antipsychotics: anticonvulsant effect antagonised. Orlistat: possibly increased risk of convulsions.

Technology Process of Tiagabine

There total 18 articles about Tiagabine 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: 90.0%

ethyl (R)-1-<4,4-bis(3-methyl-2-thienyl)-3-butenyl>-3-piperidinecarboxylate (145821-58-5) → tiagabine (115103-54-3,109857-64-9)

Guidance literature:

With hydrogenchloride; In water;

Reference yield: 85.0%

→ tiagabine (115103-54-3,109857-64-9)

Guidance literature:

Reference yield:

tiagabine hydrochloride (145821-59-6) → tiagabine (115103-54-3,109857-64-9)

Guidance literature:

With sodium hydrogencarbonate; In water; at 20 ℃; for 3h; Product distribution / selectivity;

upstream raw materials:

ethyl (R)-1-<4,4-bis(3-methyl-2-thienyl)-3-butenyl>-3-piperidinecarboxylate

tiagabine hydrochloride

2-bromo-3-methylthiophene

3-methyl-2-thiophenecarboxaldehdye

Refernces

• 1、 -. "Crystalline and amorphous forms of tiagabine". Page/Page column 13. . Retrieved 2008/06/13.
• 2、 -. "Modified form of the R(-)-N-(4,4-di(3-methylthien-2-yl)but-3-enyl)-nipecotic acid hydrochloride". . . Retrieved 2008/06/13.