TONABERSAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H19ClFNO4
Molecular Weight	391.821
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)C1=CC2=C(OC(C)(C)[C@@H](O)[C@H]2NC(=O)C3=CC=C(F)C(Cl)=C3)C=C1

InChI

InChIKey=XLIIRNOPGJTBJD-ROUUACIJSA-N

InChI=1S/C20H19ClFNO4/c1-10(24)11-5-7-16-13(8-11)17(18(25)20(2,3)27-16)23-19(26)12-4-6-15(22)14(21)9-12/h4-9,17-18,25H,1-3H3,(H,23,26)/t17-,18-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10021946
Curator's Comment: description was created on several sources, including https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142555/

Tonabersat is a unique compound with demonstrated activity as a gap-junction inhibitor in animal studies. In preclinical and clinical trials, tonabersat was well tolerated, with no cardiovascular effects; the pharmacokinetic profile suggested its usefulness in the prophylaxis of migraine. The basis of its high efficacy is inhibiting neuronal hyperexcitability and trigeminal nerve stimulated neurogenic inflammation in rodent models. Tonabersat inhibits the CSD (cortical spreading depression) that is believed to underlie the aura of migraine.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gap junction 4 Target ID: map04540 Sources: www.ncbi.nlm.nih.gov/pubmed/24611055	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine with aura 11 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19570717	Preventing		Phase II 1132	Unknown Approved Use Unknown
Migraine without aura 7 Sources: https://clinicaltrials.gov/ct2/show/NCT00534560	Preventing		Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
80 mg single, oral (unknown) Highest studied dose Dose: 80 mg Route: oral Route: single Dose: 80 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19723122	unhealthy n = 109 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 109 Sources: https://pubmed.ncbi.nlm.nih.gov/19723122	Other AEs: Dizziness, Nausea... Other AEs: Dizziness (5.5%) Nausea (4.6%) Vertigo (4.6%) Somnolence (0.9%) Abdominal pain (0.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/19723122
40 mg 1 times / day multiple, oral (total daily dose) Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19222510	unhealthy n = 58 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 58 Sources: https://pubmed.ncbi.nlm.nih.gov/19222510	Disc. AE: dizziness, nausea... AEs leading to discontinuation/dose reduction: dizziness (1 pt) nausea (2 patients) nausea (1 pt) Drowsiness (severe, 1 pt) headache (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19222510

AEs

AE	Significance	Dose	Population
Abdominal pain	0.9%	80 mg single, oral (unknown) Highest studied dose Dose: 80 mg Route: oral Route: single Dose: 80 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19723122	unhealthy n = 109 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 109 Sources: https://pubmed.ncbi.nlm.nih.gov/19723122
Somnolence	0.9%	80 mg single, oral (unknown) Highest studied dose Dose: 80 mg Route: oral Route: single Dose: 80 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19723122	unhealthy n = 109 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 109 Sources: https://pubmed.ncbi.nlm.nih.gov/19723122
Nausea	4.6%	80 mg single, oral (unknown) Highest studied dose Dose: 80 mg Route: oral Route: single Dose: 80 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19723122	unhealthy n = 109 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 109 Sources: https://pubmed.ncbi.nlm.nih.gov/19723122
Vertigo	4.6%	80 mg single, oral (unknown) Highest studied dose Dose: 80 mg Route: oral Route: single Dose: 80 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19723122	unhealthy n = 109 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 109 Sources: https://pubmed.ncbi.nlm.nih.gov/19723122
Dizziness	5.5%	80 mg single, oral (unknown) Highest studied dose Dose: 80 mg Route: oral Route: single Dose: 80 mg Sources: https://pubmed.ncbi.nlm.nih.gov/19723122	unhealthy n = 109 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 109 Sources: https://pubmed.ncbi.nlm.nih.gov/19723122
dizziness	1 pt Disc. AE	40 mg 1 times / day multiple, oral (total daily dose) Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19222510	unhealthy n = 58 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 58 Sources: https://pubmed.ncbi.nlm.nih.gov/19222510
headache	1 pt Disc. AE	40 mg 1 times / day multiple, oral (total daily dose) Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19222510	unhealthy n = 58 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 58 Sources: https://pubmed.ncbi.nlm.nih.gov/19222510
nausea	1 pt Disc. AE	40 mg 1 times / day multiple, oral (total daily dose) Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19222510	unhealthy n = 58 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 58 Sources: https://pubmed.ncbi.nlm.nih.gov/19222510
nausea	2 patients Disc. AE	40 mg 1 times / day multiple, oral (total daily dose) Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19222510	unhealthy n = 58 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 58 Sources: https://pubmed.ncbi.nlm.nih.gov/19222510
Drowsiness	severe, 1 pt Disc. AE	40 mg 1 times / day multiple, oral (total daily dose) Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19222510	unhealthy n = 58 Health Status: unhealthy Condition: migraine Sex: M+F Food Status: UNKNOWN Population Size: 58 Sources: https://pubmed.ncbi.nlm.nih.gov/19222510

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0020KT	https://www.1pchem.com/search?query=1P0020KT
AK Scientific	X6315	https://aksci.com/item_detail.php?cat=X6315
Alfa Chemistry	ACM175013840	http://www.alfa-chemistry.com/search.aspx?q=ACM175013840
BLD Pharm	BD154391	http://www.bldpharm.com/search/Search.html?keyword=BD154391
BOC Sciences	175013-84-0	http://www.bocsci.com/description.asp?cas=175013-84-0
Cayman Chemical	19796	http://www.caymanchem.com/app/template/Product.vm/catalog/19796
Chem Scene	CS-0676	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0676
KeyOrganics	ES-0039	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=ES-0039
Lab Network	LN01312354	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01312354
MedChem Express	HY-15204	https://www.medchemexpress.com/search.html?q=HY-15204&ft=&fa=&fp=
MolPort	MolPort-003-850-578	https://www.molport.com/shop/molecule-link/MolPort-003-850-578
MuseChem	I002283	https://www.musechem.com/product/I002283.html
Tetrahedron	TS80773	http://www.thsci.com/search.do?q=TS80773
Toronto Research Chemicals	T539500	https://www.trc-canada.com/product-detail/?CatNum=T539500
eMolecules	11312708	https://orderbb.emolecules.com/search/#?query=11312708
eMolecules	275105177	https://orderbb.emolecules.com/search/#?query=275105177
eMolecules	300125756	https://orderbb.emolecules.com/search/#?query=300125756
mcule	MCULE-1253821635	https://mcule.com/MCULE-1253821635/
mcule	MCULE-6929365328	https://mcule.com/MCULE-6929365328/
mcule	MCULE-8632127641	https://mcule.com/MCULE-8632127641/

PubMed

Title	Date	PubMed
Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent.	1999 Jan 18	10021946
The potential anti-migraine compound SB-220453 does not contract human isolated blood vessels or myocardium; a comparison with sumatriptan.	2000 Jul	11075836
SB-220453, a potential novel antimigraine agent, inhibits nitric oxide release following induction of cortical spreading depression in the anaesthetized cat.	2000 Mar	10961764
Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes.	2001 Apr	11264249
A double-blind study of SB-220453 (Tonerbasat) in the glyceryltrinitrate (GTN) model of migraine.	2004 Oct	15377319

Patents

Sample Use Guides

In Vivo Use Guide

Take 40 mg daily for 12 weeks.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

TONABERSAT

Official Name

English

tonabersat [INN]

Common Name

English

Tonabersat [WHO-DD]

Common Name

English

SB-220453

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C264