CAS 49763-96-4|Stiripentol

Introduction：Basic information about CAS 49763-96-4|Stiripentol, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Stiripentol BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Articles37
7. Synonyms

Common Name	Stiripentol
CAS Number	49763-96-4	Molecular Weight	234.291
Density	1.1±0.1 g/cm3	Boiling Point	365.4±11.0 °C at 760 mmHg
Molecular Formula	C₁₄H₁₈O₃	Melting Point	73-74ºC
MSDS	ChineseUSA	Flash Point	174.8±19.3 °C
Symbol	GHS07	Signal Word	Warning

Names

Name	Stiripentol
Synonym	More Synonyms

Stiripentol BiologicalActivity

Description	Stiripentol (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to NCLB mediatated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with Ki of 1.59±0.07 and 0.516±0.065 μM and IC50 of 1.58 and 3.29 μM, respectively.
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>Cytochrome P450Research Areas >>Neurological Disease
Target	IC50: 1.58 μM (CYP3A4), 3.29 μM (CYP2C19)[1] Ki: 1.59±0.07μM (CYP3A4), 0.516±0.065 μM (CYP2C19)[1]
In Vitro	Stiripentol (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to N-desmethylclobazam (NCLB) mediated by CYP3A4 (noncompetitively) and CYP2C19 (competitively). The inhibition of CLB demethylation by Stiripentol (STP) is best described by a noncompetitive inhibition model with apparent Ki=1.6 μM for the cDNA-expressing CYP3A4 and by a competitive inhibition model with Ki=0.52 μM for the cDNA-expressing CYP2C19. Formation of OH-NCLB from NCLB by cDNA-expressing CYP2C19 is competitively inhibited by Stiripentol (STP) with a Ki=0.14 μM[1].
In Vivo	In mice treating with Stiripentol (STP) monotherapy, the difference between BT1 (39.67±1.09°C) and BT2 (41.32±1.05°C) reaches statistical significance (t=3.097, p<0.05). The difference in BT2 between Stiripentol (STP) monotherapy and CLB monotherapy is statistically significant (t=2.615, p<0.05). In mice treating with Stiripentol (STP)+CLB combination therapy, the difference between BT1 (40.18±0.58°C) and BT2 (43.03±0.49°C) reaches statistical significance (t=10.44, p<0.01)[2].
Cell Assay	The inhibition constants (apparent Ki) of Stiripentol (STP) for CLB demethylation by CYP3A4 and CYP2C19 are determined using various concentrations of CLB (2, 10, 20, 40, 60, and 100 μM) with increasing concentrations of Stiripentol (STP) (0, 0.5, 1, 2, and 5 μM). Concerning NCLB hydroxylation by CYP2C19, the apparent Ki is similarly determined with different concentrations of NCLB (1.5, 4, 6, 8, 12, and 14 μM) and STP (0, 0.1, 0.5, 1, and 2 μM). IC50 values are determined by coincubation of the substrate at concentration in the range of the therapeutic plasma concentrations (2 μM CLB or 14 μM NCLB) with increasing concentrations of Stiripentol (STP) (0.001, 0.002, 0.005, 0.01, 0.05, 0.1, 0.25, 2, 5, and 10 μM)[1].
Animal Admin	Two age groups, p1M (n=18, age 4 weeks) and p5M (n=18, age 5-10 months), of Scn1aRX/+ mice are assigned in this experiment. Both groups are divided randomly into three subgroups (n=6), and each subgroup is administered Stiripentol (STP) (300 mg/kg) alone, CLB (6.62 mg/kg) alone, or a combination of Stiripentol (STP) (p1M; 150 mg/kg, p5M; 300 mg/kg) and CLB (6.62 mg/kg). All drugs are administered by intraperitoneal injection (i.p.) after a 48-h recovery from baseline seizure study. Blood samples are collected at 1 h and 20 min after administration of CLB or STP+CLB for measurement of plasma concentrations of CLB and N-desmethylclobazam, respectively[2].
References	[1]. Giraud C, et al. In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism.Drug Metab Dispos. 2006 Apr;34(4):608-11. Epub 2006 Jan 13. [2]. Cao D, et al. Efficacy of stiripentol in hyperthermia-induced seizures in a mouse model of Dravet syndrome. Epilepsia. 2012 Jul;53(7):1140-5.

Chemical & Physical Properties

Density	1.1±0.1 g/cm3
Boiling Point	365.4±11.0 °C at 760 mmHg
Melting Point	73-74ºC
Molecular Formula	C₁₄H₁₈O₃
Molecular Weight	234.291
Flash Point	174.8±19.3 °C
Exact Mass	234.125595
PSA	38.69000
LogP	3.39
Vapour Pressure	0.0±0.9 mmHg at 25°C
Index of Refraction	1.579
InChIKey	IBLNKMRFIPWSOY-FNORWQNLSA-N
SMILES	CC(C)(C)C(O)C=Cc1ccc2c(c1)OCO2

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: SB3393000

CHEMICAL NAME :: 1-Penten-3-ol, 4,4-dimethyl-1-(3,4-methylenedioxyphenyl)-

CAS REGISTRY NUMBER :: 49763-96-4

BEILSTEIN REFERENCE NO. :: 1313047

LAST UPDATED :: 199612

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C14-H18-O3

MOLECULAR WEIGHT :: 234.32

WISWESSER LINE NOTATION :: T56 BO DO CHJ G1U1YQX1&1&1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >3 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 34,199,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1471 mg/kg

TOXIC EFFECTS :: Behavioral - anticonvulsant

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 34,199,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 34,199,1984

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1250 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: EJMCA5 European Journal of Medicinal Chemistry--Chimie Therapeutique. (Editions Scientifiques Elsevier, 29 rue Buffon, F-75005, Paris, France) V.9- 1974- Volume(issue)/page/year: 13,41,1978

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 72 mg/kg

TOXIC EFFECTS :: Behavioral - anticonvulsant

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 34,199,1984 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6400 mg/kg

SEX/DURATION :: female 2 week(s) pre-mating - 18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987- Volume(issue)/page/year: 7,439,1993

Safety Information

Symbol	GHS07
Signal Word	Warning
Hazard Statements	H302
RIDADR	NONH for all modes of transport

Articles37

The efficacy of bromides, stiripentol and levetiracetam in two patients with malignant migrating partial seizures in infancy.

Epileptic Disord. 13(1) , 22-6, (2011)

The syndrome of malignant migrating partial seizures in infancy is a devastating, age-specific, epileptic encephalopathy, which still presents an aetiological, pathophysiological and therapeutic probl...

Stiripentol in refractory status epilepticus.

Epilepsia 54 Suppl 6 , 103-5, (2013)

Benzodiazepines (BZDs), which enhance γ-aminobutyric acid (GABAA ) receptor-mediated inhibition, are the first-line therapy for treatment of status epilepticus (SE). However, pharmacoresistance to BZD...

[Clinical and genetic diagnosis of Dravet syndrome: report of 20 cases].

Ideggyogy. Sz. 61(11-12) , 402-8, (2008)

Severe myoclonic epilepsy in infancy (SMEI; Dravet's syndrome) is a malignant epilepsy syndrome characterized by prolonged febrile hemiconvulsions or generalized seizures starting in the first year of...

Synonyms

1-(1,3-Benzodioxol-5-yl)-4,4-dimethyl-1-penten-3-ol

4,4-Dimethyl-1-(3,4-methylenedioxyphenyl)-1-penten-3-ol

4,4-dimethyl-1-[3,4(methylenedioxy)-phenyl]-1-penten-3-ol,Diacomit

Stiripentol

Stiripentol [USAN:INN]

1-Penten-3-ol, 1-(1,3-benzodioxol-5-yl)-4,4-dimethyl-, (1E)-

(1E)-1-(1,3-Benzodioxol-5-yl)-4,4-dimethyl-1-penten-3-ol

(E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-ol

UNII:R02XOT8V8I

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