US3318772A - Compositions and methods of treating convulsant seizures - Google Patents
Compositions and methods of treating convulsant seizures Download PDFInfo
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- US3318772A US3318772A US543809A US54380966A US3318772A US 3318772 A US3318772 A US 3318772A US 543809 A US543809 A US 543809A US 54380966 A US54380966 A US 54380966A US 3318772 A US3318772 A US 3318772A
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- Prior art keywords
- thiosemicarbazide
- seizures
- convulsant
- compound
- animals
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- 239000003179 convulsant agent Substances 0.000 title claims description 16
- 238000000034 method Methods 0.000 title claims description 12
- 206010010904 Convulsion Diseases 0.000 title description 15
- 239000000203 mixture Substances 0.000 title description 12
- 150000001875 compounds Chemical class 0.000 claims description 20
- 241001465754 Metazoa Species 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000012360 testing method Methods 0.000 description 9
- 150000003583 thiosemicarbazides Chemical class 0.000 description 9
- 239000001961 anticonvulsive agent Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 229960003965 antiepileptics Drugs 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 230000001773 anti-convulsant effect Effects 0.000 description 5
- -1 4-(2-methylbenzyl)-3-thiosemicarbazide Chemical compound 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 229940125681 anticonvulsant agent Drugs 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- DFWYQZYTNMMADI-UHFFFAOYSA-N 1-amino-3-(2,3-dimethylphenyl)thiourea Chemical compound CC1=CC=CC(NC(=S)NN)=C1C DFWYQZYTNMMADI-UHFFFAOYSA-N 0.000 description 2
- YTRJQDFRZLKDHZ-UHFFFAOYSA-N 1-amino-3-(2,4-dimethylphenyl)thiourea Chemical compound CC1=CC=C(NC(=S)NN)C(C)=C1 YTRJQDFRZLKDHZ-UHFFFAOYSA-N 0.000 description 2
- VASTZUGVKHOFPE-UHFFFAOYSA-N 1-isothiocyanato-2,3-dimethylbenzene Chemical compound CC1=CC=CC(N=C=S)=C1C VASTZUGVKHOFPE-UHFFFAOYSA-N 0.000 description 2
- 208000034308 Grand mal convulsion Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- AKMOMQJDVWEYEZ-UHFFFAOYSA-N (2,3-dimethylanilino)thiourea Chemical compound CC1=CC=CC(NNC(N)=S)=C1C AKMOMQJDVWEYEZ-UHFFFAOYSA-N 0.000 description 1
- CVYAVYZOGZJQHT-UHFFFAOYSA-N 1-amino-3-(2-ethylphenyl)thiourea Chemical compound CCC1=CC=CC=C1NC(=S)NN CVYAVYZOGZJQHT-UHFFFAOYSA-N 0.000 description 1
- OVAFDUCMHLFDIG-UHFFFAOYSA-N 1-ethyl-2-isothiocyanatobenzene Chemical compound CCC1=CC=CC=C1N=C=S OVAFDUCMHLFDIG-UHFFFAOYSA-N 0.000 description 1
- HOHSBFCSOARUBF-UHFFFAOYSA-N 1-isothiocyanato-2,4-dimethylbenzene Chemical compound CC1=CC=C(N=C=S)C(C)=C1 HOHSBFCSOARUBF-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000037012 Psychomotor seizures Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
- A61K31/175—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine having the group, >N—C(O)—N=N— or, e.g. carbonohydrazides, carbazones, semicarbazides, semicarbazones; Thioanalogues thereof
Definitions
- the present invention relates to the treatment of convulsant seizures in animals. More particularly, it relates to the use of certain derivatives of thiosemicarbazides which heretofore have not either been employed in or recognized as effective for the treatment of convulsant seizures, e.g. epileptic seizures.
- convulstant seizures are those associated with epilepsy, of which there are three distinct types-grand mal, petite mal and psychomotor seizures. Any one, or any combination, of these types of seizures may occur in epilepsy cases. A large number of these cases can be controlled with known anticonvulsant agents. However, in some cases, the so-called refractory cases, there is no completely effective therapy. As a consequence, the search has not ceased for new anticonvulsant agents.
- R is a member selected from the group consisting of:
- thiosemicarbazide derivatives that have been found useful in the present invention may be conveniently synthesized by the treatment of an appropriate isothiocyanate with hydrazine as illustrated in the following equation, although the invention is not limited to this specific method of preparation:
- EXAMPLE II 4-(2,4-dimethylphenyl)-3-thi0semicarbazide The method of Example I was followed with the exception that 0.05 mole of 2,4- dimethylphenyl isothiocyanate was employed in place of the 2,3-dimethylphenyl isothiocyanate. Upon recrystallization from methanol, a yield of 7.4 g. of 4-(2,4-dimethylphenyl)-3-thiosemicarbazide was obtained in the form of a white solid which had a melting point of 152 C- EXAMPLE III 4- (Z-eZhyZphenyl) -3-thz0semicarbazide To a mixture of 30 m1.
- EXAMPLE IV 4- (Z-methylbenzyl) -3-thi0se'micarbazide T o a mixture of 30 ml. of 85% hydrazine hydrate and 40 ml. of methanol was added dropwise with stirring, 16.3 g. (0.1 mole) of 2-1nethylbenzyl isothiocyanate in 40 ml. of methanol. The precipitate was collected and washed with petroleum ether. The crude material was recrystallized from methanol and then from butanol. Upon drying, 15.5 g. of 4-(2-methylbenzyl)-3-thiosemicarbazide in the form of a white solid was obtained having a melting point of 153-154 C.
- the thiosemicarbazide derivatives are preferably employed in the method of the invention in the form of tablets, powders, capsules or other therapeutic dosage forms.
- the active anticonvulsant material may be admixed with a wide variety of pharmaceutical diluents which are not incompatible with the active ingredients.
- these therapeutic dosage forms it is preferable to use at least about 10 mg. of the active compound per dose.
- EXAMPLE V the results of tests are reported in Table I, below, in which white mice were subjected to the established and conventional convulsant producing procedure known as electroshock. Anticonvulsant activity was TAB LE I AED50 EDsO ALD50 TD50. 3-Thiosemicarbazide ME S. ME S. 7 day. oral Derivative i.p. oral i.p.
- one of the test parameters employed is the ED which represents in milligrams the oral dose of the medicament per kilogram of body weight of the test animal, which when administered to the test animals will protect 50% of them from the effects of the electroshock. In'determining the ED at least ten animals are employed at each level for each compound being tested. Another test parameter reported in Table I is the AED which is the approximate ED obtained when the compound being tested is administered to the test animals intraperitoneally.
- the above table also refers to the ALD which is the Approximate Lethal Dose, which when given intraperitoneally will kill 50% of the test animals.
- the T D referred to in the table is the amount of anticonvulsant material per kilogram of body weight which when administered orally will induce a toxic reaction in 50% of the animals.
- the thiosemicarbazide derivatives of this invention have a pronounced activity in protecting the animals against the electroshock induced seizures which are generally recognized as corresponding to grand mal convulsant seizures.
- the compound 4-phenyl thiosemicarbazide was convulsant to 50% of white mice given an oral dose at 29.5 mg./kg. and lethal to 50% of the mice at only 40 mg./ kg. in the same test; the compound 4-methyl thiosemicarbazide was convulsant to 50% of white mice given an oral dose of 15.5 mg./kg.
- the amount of the anticonvulsant material which would normally be administered is primarily determined by the physical characteristics of the recipient and severity of the convulsant seizures. Obviously, the amount of the particular compound to be administered must be an effective amount, i.e., an amount which is medically beneficial but does not present toxic effects which overweigh the advantages which accompany its use. It would be expected that the adult human dosage would normally range upwardly from about 10 milligrams of the active compound. The exact dosage, of course, would depend on the physical characteristics of the recipient, the severity of the seizures and such other factors such as other medication. The dosage for other animals such as dogs would likewise be dependent upon a variety of factors and could to some extent be determined by trial testing.
- R is a member selected from the group consisting of:
- composition for preventing convulsant seizures in animals comprising at least 10 mg. of an active compound having the following formula:
- R is a member selected from the group consisting of:
- a pharmaceutical diluent in therapeutic dosage form selected from the group consisting of powders, tablets, and capsules.
- composition of matter of claim 6 in which the active compound is 4-(2-methylbenzyl)-3-thiosemicarbazide.
- composition of matter of claim 6 in which the active compound is 4-(2,3-dimethylphenyl)-3-thiosemicarbazide.
- composition of matter of claim 6 in which the active compound is 4-(2,4-dimethylphenyl)-2-thiosemicarbazide.
- composition of matter of claim 6 in which the active compound is 4-(2-cthylphenyl)-3-thiosemicarbazide.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
United States Patent M 3,318,772 COMPOSITIONS AND METHODS OF TREATING CONVULSANT SEIZURES Arthur Berger, Skokie, and Edeltraut E. Borgaes, Chicago, 111., assignors to Baxter Laboratories, Inc., Morton Grove, 11]., a corporation of Delaware No Drawing. Filed Apr. 20, 1966, Ser. No. 543,809 11 Claims. (Cl. 167-65) This case is a continuation-in-part of co-pending application Serial No. 336,614, filed January 9, 1964, now abandoned.
The present invention relates to the treatment of convulsant seizures in animals. More particularly, it relates to the use of certain derivatives of thiosemicarbazides which heretofore have not either been employed in or recognized as effective for the treatment of convulsant seizures, e.g. epileptic seizures.
The most familiar type of convulstant seizures are those associated with epilepsy, of which there are three distinct types-grand mal, petite mal and psychomotor seizures. Any one, or any combination, of these types of seizures may occur in epilepsy cases. A large number of these cases can be controlled with known anticonvulsant agents. However, in some cases, the so-called refractory cases, there is no completely effective therapy. As a consequence, the search has not ceased for new anticonvulsant agents.
It has now been found that convulsant seizures 'in white mice can be controlled or prevented by administering certain derivatives of thiosemicarbazides which have the following formula:
H RN(||3NHNH2 s in which R is a member selected from the group consisting of:
CH3 (EHzCHa CllHa CH3 Q and Specific compounds which are useful in the method of the present invention are:
4- (Z-methylbenzyl -3-thiosemicarb azide,
4- (2,3-dimethyl-phenyl -3-thiosemicarb azide,
4- 2,4dimethylphenyl -3 -thi0semicarb azide, and 4-(2-ethy1phenyl) -3 -thiosemicarbazide.
The discovery that the above named thiosemicarbazide derivatives are effective as anticonvulsant agents is completely unexpected in view of the fact that all other thiosemicarbazide type compounds previously reported on are either known convulsants or have no central nervous system activity whatsoever. In no instance has the literature reported anticonvulsant efficacy for such other compounds. In view of the usefulness of the thiosemicarbazide derivatives of this invention in animals, these com pounds hold very good promise as effective agents in the treatment of convulsant seizures in man.
The thiosemicarbazide derivatives that have been found useful in the present invention may be conveniently synthesized by the treatment of an appropriate isothiocyanate with hydrazine as illustrated in the following equation, although the invention is not limited to this specific method of preparation:
3,318,772 Patented May 9, 1967 'in which R is as previously defined.
The following examples further illustrate the syntheses of the thiosemicarbazide derivatives employed in the pres ent invention and the use of these compounds in the treatment of convulsant seizures.
EXAMPLE I 4-(2,3-dimethylphenyl)-3-thi0semicarbazide To a mixture of 5.0 m1. of hydrazine hydrate in 50 ml. of methanol was added dropwise 8.2 g. (0.05 mole) of 2,3-dimethylphenyl isothiocyanate in 25 ml. of methanol. A solid formed as the mixture became heated by the exothermic reaction. The solid was collected on a filter and Washed with petroleum ether. On recrystallization of the solid from alcohol, 6.9 g. of 4-(2 ,3-dimethylphenyl)-3-thiosemicarbazide was obtained in the form of a white solid having a melting point of 158- 159 C.
EXAMPLE II 4-(2,4-dimethylphenyl)-3-thi0semicarbazide The method of Example I was followed with the exception that 0.05 mole of 2,4- dimethylphenyl isothiocyanate was employed in place of the 2,3-dimethylphenyl isothiocyanate. Upon recrystallization from methanol, a yield of 7.4 g. of 4-(2,4-dimethylphenyl)-3-thiosemicarbazide was obtained in the form of a white solid which had a melting point of 152 C- EXAMPLE III 4- (Z-eZhyZphenyl) -3-thz0semicarbazide To a mixture of 30 m1. of 85% hydrazine hydrate and 150 ml. of methanol was added dropwise with stirring, 16.3 g. (0.1 mole) of 2-ethyl-phenyl isothiocyanate in 50 ml. of methanol. The mixture was heated to 55 C. for 1 hour, and after cooling to room temperature, the solid was collected. After recrystallization from benzene with carbon treatment, a white solid was obtained. Upon drying, 12.4 g. of the compound was obtained, having a melting point of 12913l C. The identity of the compound was confirmed as 4-(2-ethylphenyl)-3-thiosemicarbazide by elemental analysis as follows:
Calculated: carbon, 55.35%; hydrogen, 6.71%; sulfur, 16.42%. Found: carbon, 55.52%; hydrogen, 6.77%; sulfur, 16.49%.
EXAMPLE IV 4- (Z-methylbenzyl) -3-thi0se'micarbazide T o a mixture of 30 ml. of 85% hydrazine hydrate and 40 ml. of methanol was added dropwise with stirring, 16.3 g. (0.1 mole) of 2-1nethylbenzyl isothiocyanate in 40 ml. of methanol. The precipitate was collected and washed with petroleum ether. The crude material was recrystallized from methanol and then from butanol. Upon drying, 15.5 g. of 4-(2-methylbenzyl)-3-thiosemicarbazide in the form of a white solid was obtained having a melting point of 153-154 C.
The thiosemicarbazide derivatives are preferably employed in the method of the invention in the form of tablets, powders, capsules or other therapeutic dosage forms. In such forms the active anticonvulsant material may be admixed with a wide variety of pharmaceutical diluents which are not incompatible with the active ingredients. In these therapeutic dosage forms it is preferable to use at least about 10 mg. of the active compound per dose.
EXAMPLE V In this example, the results of tests are reported in Table I, below, in which white mice were subjected to the established and conventional convulsant producing procedure known as electroshock. Anticonvulsant activity was TAB LE I AED50 EDsO ALD50 TD50. 3-Thiosemicarbazide ME S. ME S. 7 day. oral Derivative i.p. oral i.p.
4-(2-methylbenzyD- 1 9 l2. 250 53 4- (2.3-dimotliylphenyl)- 10 34 500 108 4-(2A-dimcthylphenyD- 11 21 300 107 4-(2-ethylplienyl) 11 31 150 280 In the above table, one of the test parameters employed is the ED which represents in milligrams the oral dose of the medicament per kilogram of body weight of the test animal, which when administered to the test animals will protect 50% of them from the effects of the electroshock. In'determining the ED at least ten animals are employed at each level for each compound being tested. Another test parameter reported in Table I is the AED which is the approximate ED obtained when the compound being tested is administered to the test animals intraperitoneally.
The above table also refers to the ALD which is the Approximate Lethal Dose, which when given intraperitoneally will kill 50% of the test animals. The T D referred to in the table is the amount of anticonvulsant material per kilogram of body weight which when administered orally will induce a toxic reaction in 50% of the animals.
From the data in Table I it is seen that the thiosemicarbazide derivatives of this invention have a pronounced activity in protecting the animals against the electroshock induced seizures which are generally recognized as corresponding to grand mal convulsant seizures. By way of comparison, the compound 4-phenyl thiosemicarbazide was convulsant to 50% of white mice given an oral dose at 29.5 mg./kg. and lethal to 50% of the mice at only 40 mg./ kg. in the same test; the compound 4-methyl thiosemicarbazide was convulsant to 50% of white mice given an oral dose of 15.5 mg./kg.
The amount of the anticonvulsant material which would normally be administered is primarily determined by the physical characteristics of the recipient and severity of the convulsant seizures. Obviously, the amount of the particular compound to be administered must be an effective amount, i.e., an amount which is medically beneficial but does not present toxic effects which overweigh the advantages which accompany its use. It would be expected that the adult human dosage would normally range upwardly from about 10 milligrams of the active compound. The exact dosage, of course, would depend on the physical characteristics of the recipient, the severity of the seizures and such other factors such as other medication. The dosage for other animals such as dogs would likewise be dependent upon a variety of factors and could to some extent be determined by trial testing.
As will be readily apparent to those skilled in the art, other examples of the herein-defined invention can be devised by various modifications, variations and adaptations without departing from the spirit and scope of the invention after reading the foregoing specification and the Claims appended hereto. All such modifications, variations and adaptations are included within the scope of the invention as defined in the appended claims.
What we claim is:
1. The method of preventing convulsant seizures in animals which com-prises administering to such animals an effective amount of a compound having the formula:
H RNfiJNI-INHB in which R is a member selected from the group consisting of:
(ll-Is (31320113 CHs CH3 and (EH: CH3- 2. The method of claim 1 in which the compound is 4- Z-methylbenzyl) -3-thiosemicarb azide.
3. The method of claim 1 in which the compound is 4- 2, 3-dirnethylphenyl -3-thiosemicarbazide.
4. The method of claim 1 in which the compound is 4- (2,4-dimethylphenyl) -3 -thiosemicarb azide.
5. The method of claim 1 in which the compound is 4- Z-ethylphenyl -3 -thiosemicarb azide.
6. A composition for preventing convulsant seizures in animals comprising at least 10 mg. of an active compound having the following formula:
in which R is a member selected from the group consisting of:
(IJI'I; CllHrCHs ([3113 (FE:
and
in combination with a pharmaceutical diluent in therapeutic dosage form selected from the group consisting of powders, tablets, and capsules.
7'. The composition of matter of claim 6 in which the active compound is 4-(2-methylbenzyl)-3-thiosemicarbazide.
8. The composition of matter of claim 6 in which the active compound is 4-(2,3-dimethylphenyl)-3-thiosemicarbazide.
9. The composition of matter of claim 6 in which the active compound is 4-(2,4-dimethylphenyl)-2-thiosemicarbazide.
10. The composition of matter of claim 6 in which the active compound is 4-(2-cthylphenyl)-3-thiosemicarbazide.
11. 4- (Z-ethylphenyl -3-thiosemicarbazide.
References Cited by the Examiner UNITED STATES PATENTS 2,658,062 11/1953 Jones 260-132 ALBERT T. MEYERS, Primary Examiner.
STANLEY I. FRIEDMAN, Assistant Examiner.
UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,318, 772 May 9, 1967 Arthur Berger et a1 It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.
Column 4, lines 58 and S9, for "4-(2,4dimethylphenyl)- Z-thiosemicarbazide" read 4-(2,4-dimethy1pheny1) -3 thiosemicarbazide Signed and sealed this 21st day of November 1967.
(SEAL) Attest:
EDWARD J. BRENNER Edward M. Fletcher, Jr.
Commissioner of Patents Attesting Officer
Claims (1)
1. THE METHOD OF PREVENTING CONVULSANT SEIZURES IN ANIMALS WHICH COMPRISES ADMINISTERING TO SUCH ANIMALS AN EFFECTIVE AMOUNT OF A COMPOUND HAVING THE FROMULA:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US543809A US3318772A (en) | 1964-01-09 | 1966-04-20 | Compositions and methods of treating convulsant seizures |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33661464A | 1964-01-09 | 1964-01-09 | |
| US543809A US3318772A (en) | 1964-01-09 | 1966-04-20 | Compositions and methods of treating convulsant seizures |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3318772A true US3318772A (en) | 1967-05-09 |
Family
ID=26990295
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US543809A Expired - Lifetime US3318772A (en) | 1964-01-09 | 1966-04-20 | Compositions and methods of treating convulsant seizures |
Country Status (1)
| Country | Link |
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| US (1) | US3318772A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4256661A (en) * | 1978-05-09 | 1981-03-17 | Mobay Chemical Corporation | Production of thiosemicarbazide |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2658062A (en) * | 1949-09-17 | 1953-11-03 | Standard Oil Dev Co | Mineral oil additive |
-
1966
- 1966-04-20 US US543809A patent/US3318772A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2658062A (en) * | 1949-09-17 | 1953-11-03 | Standard Oil Dev Co | Mineral oil additive |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4256661A (en) * | 1978-05-09 | 1981-03-17 | Mobay Chemical Corporation | Production of thiosemicarbazide |
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