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Zonisamide

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Name

Zonisamide

EINECS 200-659-6
CAS No. 68291-97-4 Density 1.509 g/cm3
PSA 94.57000 LogP 2.39740
Solubility N/A Melting Point 275°C dec
Formula C8H8N2O3S Boiling Point 457.2 °C at 760 mmHg
Molecular Weight 212.229 Flash Point 230.3 °C
Transport Information N/A Appearance off-white powder
Safety 7-16-36/37-45 Risk Codes 22
Molecular Structure Molecular Structure of 68291-97-4 (Zonisamide) Hazard Symbols HarmfulXn
Synonyms

CI-912;benzo[d]isoxazol-3-ylmethanesulfonamide;Zonisamide [USAN:BAN:INN:JAN];Excegran (TN);3-(Sulfamoylmethyl)-1,2-benzisoxazole;CI 912;Zonisamide (JAN/USAN);Zonegran;1,2-Benzisoxazole-3-methanesulfonamide;Zonisamida [Spanish];AD-810;Excegran;Exceglan;Excegram;Zonisamidum [Latin];AD 810 (sulfonamide);PD 110843;

Article Data 17

Zonisamide Synthetic route

73101-65-2

1,2-benzoxazol-3-ylmethanesulfonyl chloride

68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

Conditions
ConditionsYield
With ammonia In toluene at 2 - 15℃; pH=9;91.25%
With ammonia In toluene at 2℃; pH=9; Product distribution / selectivity;91.6%
With ammonium carbonate In butanone for 1h; Heating / reflux;77.8%
73101-65-2

1,2-benzoxazol-3-ylmethanesulfonyl chloride

A

68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

B

81534-20-5

1,2-benzisoxazole-3-methanesulfonic acid ammonium salt

Conditions
ConditionsYield
With ammonia In toluene at 10 - 15℃;A 85%
B n/a
With ammonia In toluene at 10 - 15℃; Product distribution / selectivity;
73101-64-1

1,2-benzisoxazole-3-methanesulfonic acid sodium salt

68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

Conditions
ConditionsYield
Stage #1: 1,2-benzisoxazole-3-methanesulfonic acid sodium salt In DMF (N,N-dimethyl-formamide); toluene at 10 - 40℃; for 2h;
Stage #2: With oxalyl dichloride In DMF (N,N-dimethyl-formamide); toluene at 10 - 18℃; for 2h;
Stage #3: With ammonia In DMF (N,N-dimethyl-formamide); toluene at 10 - 18℃; for 2h; Product distribution / selectivity;
75%
Stage #1: 1,2-benzisoxazole-3-methanesulfonic acid sodium salt In DMF (N,N-dimethyl-formamide); toluene at 10 - 40℃; for 1.5h;
Stage #2: With oxalyl dichloride In DMF (N,N-dimethyl-formamide); toluene at 10 - 18℃; for 2h;
Stage #3: With ammonia In DMF (N,N-dimethyl-formamide); toluene at 10 - 18℃; for 2h; Product distribution / selectivity;
74.5%
Stage #1: 1,2-benzisoxazole-3-methanesulfonic acid sodium salt With triethylamine; trichlorophosphate In 1,2-dichloro-ethane at 77 - 83℃; for 6h;
Stage #2: With ammonia In 1,2-dichloro-ethane at 30 - 60℃;
Multi-step reaction with 2 steps
1: phosgene; N,N-dimethyl-formamide / toluene / 4 h / 25 - 35 °C / Green chemistry
2: ammonia / 1 h / 10 - 15 °C / pH 9-10 / Green chemistry
View Scheme
4865-84-3

2-(benzo[d]isoxazol-3-yl)acetic acid

68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

Conditions
ConditionsYield
Stage #1: 2-(benzo[d]isoxazol-3-yl)acetic acid With chlorosulfonic acid; ethyl acetate In 1,2-dichloro-ethane; toluene at 20 - 80℃; for 2.58333h;
Stage #2: With sodium hydroxide In water; toluene pH=10;
Stage #3: With ammonia; triethylamine; trichlorophosphate more than 3 stages;
179242-97-8

((1-(2-fluorophenyl)vinyl)oxy)trimethylsilane

68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: triethylamine; tris(2,2'-bipyridyl)ruthenium dichloride; sulphamoyl chloride / acetonitrile / 24 h / 20 °C / Schlenk technique; Inert atmosphere; Irradiation
2: hydroxylamine hydrochloride; sodium acetate / ethanol / 12 h / 95 °C
3: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 12 h / Reflux
View Scheme

2-(2-fluorophenyl)-2-oxoethane-1-sulfonamide

68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: hydroxylamine hydrochloride; sodium acetate / ethanol / 12 h / 95 °C
2: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 12 h / Reflux
View Scheme
445-27-2

2'-Fluoroacetophenone

68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1.1: sodium iodide / acetonitrile / 0.08 h / 20 °C / Inert atmosphere
1.2: 20 °C / Inert atmosphere
2.1: triethylamine; tris(2,2'-bipyridyl)ruthenium dichloride; sulphamoyl chloride / acetonitrile / 24 h / 20 °C / Schlenk technique; Inert atmosphere; Irradiation
3.1: hydroxylamine hydrochloride; sodium acetate / ethanol / 12 h / 95 °C
4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / acetonitrile / 12 h / Reflux
View Scheme

C8H9FN2O3S

68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

Conditions
ConditionsYield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile for 12h; Reflux;52 mg
68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

10417-94-4

all cis-5,8,11,14,17-eicosapentaenoic acid

1609132-23-1

C28H36N2O4S

Conditions
ConditionsYield
Stage #1: all cis-5,8,11,14,17-eicosapentaenoic acid With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;
Stage #2: 1,2-benzisoxazole-3-methanesulfonamide In N,N-dimethyl-formamide for 2h;
75%
68291-97-4

1,2-benzisoxazole-3-methanesulfonamide

66-71-7

1,10-Phenanthroline

copper(II) choride dihydrate

64-17-5

ethanol

[CuCl2(zonisamide)(1,10-phenanthroline)EtOH].H2O

Conditions
ConditionsYield
Stage #1: 1,2-benzisoxazole-3-methanesulfonamide; ethanol With sodium hydroxide
Stage #2: 1,10-Phenanthroline; copper(II) choride dihydrate In water at 70℃; for 6h;
74%

Zonisamide Specification

The Zonisamide, with the CAS registry number 68291-97-4, is also known as 1-(1,2-Benzoxazol-3-yl)methanesulphonamide. It belongs to the product categories of Anticonvulsant; Aromatics; Heterocycles; Intermediates & Fine Chemicals; Neurochemicals; Pharmaceuticals; Sulfur & Selenium Compounds; Calcium channel; Ion channels. This chemical's molecular formula is C8H8N2O3S and molecular weight is 212.23. Its IUPAC name is called 1,2-benzoxazol-3-ylmethanesulfonamide. This chemical's classification codes are Anticonvulsant; Anticonvulsants; Antioxidants; Central Nervous System Agents; Drug / Therapeutic Agent; Protective Agents; Reproductive Effect. This chemical is off-white powder. When you are using this chemical, please be cautious about it. This chemical may cause damage to health. It is harmful if swallowed.

Physical properties of Zonisamide: (1)ACD/LogP: -0.10; (2)ACD/LogD (pH 5.5): -0.1; (3)ACD/LogD (pH 7.4): -0.1; (4)ACD/BCF (pH 5.5): 1; (5)ACD/BCF (pH 7.4): 1; (6)ACD/KOC (pH 5.5): 21.05; (7)ACD/KOC (pH 7.4): 20.91; (8)#H bond acceptors: 5; (9)#H bond donors: 2; (10)#Freely Rotating Bonds: 2; (11)Index of Refraction: 1.656; (12)Molar Refractivity: 51.66 cm3; (13)Molar Volume: 140.5 cm3; (14)Surface Tension: 71.1 dyne/cm; (15)Density: 1.509 g/cm3; (16)Flash Point: 230.3 °C; (17)Enthalpy of Vaporization: 71.73 kJ/mol; (18)Boiling Point: 457.2 °C at 760 mmHg; (19)Vapour Pressure: 1.51E-08 mmHg at 25°C.

Preparation: this chemical can be prepared by 3-bromomethyl-1,2-benzo yl different chewing (I), sodium sulfite and POCl3. This reaction will need reagent methanol.

Uses of Zonisamide: it is approved in the United States, United Kingdom, for adjunctive treatment of partial seizures in adults and in Japan for both adjunctive and monotherapy for partial seizures (simple, complex, secondarily generalized), generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures. It has also been studied for obesity with significant positive effects on body weight and there are three ongoing clinical trials for this indication. It is to be sold under the name Empatic. Zonisamide has been studied for and used as a migraine preventative medication, and has also been shown to be effective in some cases of neuropathic pain. It has also been used off-label by psychiatrists as a mood stabilizer to treat bipolar depression.

You can still convert the following datas into molecular structure:
(1)Canonical SMILES: C1=CC=C2C(=C1)C(=NO2)CS(=O)(=O)N
(2)InChI: InChI=1S/C8H8N2O3S/c9-14(11,12)5-7-6-3-1-2-4-8(6)13-10-7/h1-4H,5H2,(H2,9,11,12)
(3)InChIKey: UBQNRHZMVUUOMG-UHFFFAOYSA-N

The toxicity data is as follows:

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
dog LD50 oral 1gm/kg (1000mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

BEHAVIORAL: ATAXIA

GASTROINTESTINAL: NAUSEA OR VOMITING
Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4337, 1987.
monkey LD50 oral > 1gm/kg (1000mg/kg) AUTONOMIC NERVOUS SYSTEM: "SMOOTH MUSCLE RELAXANT (MECHANISM UNDEFINED, SPASMOLYTIC)"

GASTROINTESTINAL: NAUSEA OR VOMITING

BEHAVIORAL: ATAXIA
Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4337, 1987.
mouse LD50 intraperitoneal 699mg/kg (699mg/kg)   Arzneimittel-Forschung. Drug Research. Vol. 30, Pg. 477, 1980.
mouse LD50 intravenous 816mg/kg (816mg/kg)   Drugs in Japan Vol. -, Pg. 600, 1990.
mouse LD50 oral 1829mg/kg (1829mg/kg)   United States Patent Document. Vol. #4172896,
mouse LD50 subcutaneous 1009mg/kg (1009mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX)

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

BEHAVIORAL: ATAXIA
Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4337, 1987.
rat LD50 intraperitoneal 733mg/kg (733mg/kg)   Arzneimittel-Forschung. Drug Research. Vol. 30, Pg. 477, 1980.
rat LD50 intravenous 672mg/kg (672mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX)

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

BEHAVIORAL: ATAXIA
Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4337, 1987.
rat LD50 oral 1992mg/kg (1992mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX)

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

BEHAVIORAL: ATAXIA
Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4337, 1987.
rat LD50 subcutaneous 925mg/kg (925mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX)

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

BEHAVIORAL: ATAXIA
Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4337, 1987.

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