US3313688A - Method of producing central nervous system stimulation and anorexia - Google Patents

Method of producing central nervous system stimulation and anorexia Download PDF

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US3313688A
US3313688A US353590A US35359064A US3313688A US 3313688 A US3313688 A US 3313688A US 353590 A US353590 A US 353590A US 35359064 A US35359064 A US 35359064A US 3313688 A US3313688 A US 3313688A
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phenyl
oxazolin
central nervous
nervous system
compositions
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Jr Robert Allis Hardy
Howell Charles Frederick
Quinones Nicanor Quinones
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Wyeth Holdings LLC
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American Cyanamid Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/48—Nitrogen atoms not forming part of a nitro radical

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  • This invention rel-ates to novel pharmaceutical compositions having a therapeutic effect on the central nervous system and to methods of treatment involving such compositions.
  • the present invention comprises a pharmaceutical composition containing as a principal active central nervous system agent a S-phenyl-Z-dialkylamino-2-oxazolin-4-one of the following formula:
  • NR Rg wherein R and R are the same or different lower alkyl radicals having from 1 to 4 carbon atoms.
  • compositions containing one or more of the above compounds have been found to be highly useful central nervous system agents.
  • the new compositions of this invention show a mild stimulant action and excellent anoretic action over a wide range of doses and possess distinct advantages over other stimulant drugs such as amphetamines and pipradrol.
  • the new compositions of this invention are valuable centrally acting therapeutic agents for the management of depression.
  • Amphetamine and closely related compounds such as methamphetamine have been used as central nervous system stimulants for many years, but numerous undesirable side reactions accompany their administration. For instance, they cause more or less pronounced rise in blood pressure and there is a tendency toward developing tolerance upon continual use.
  • the compositions of the present invention do not have these serious side-effects and thus are markedly superior to the amphetamines.
  • the compositions of this invention also, even at high doses, are freeof the undesirable adrenergic and cardiovascular actions characteristic of the amphetamines. As increasing doses of the amphetamines are given, convulsions are usually observed. The compositions of this invention do not cause convulsions as the doses are increased.
  • compositions containing the active drugs are considerably more active than S-phenyl-Z- imino-4-oxo oxazolidine disclosed in United States Patent No. 2,892,753.
  • 2-dimethylamino-S-phenyl- 2 oxazolin 4-one and 2-ethylmethylamino-5-phenyl-2- oxazolin-4-one are approximately nine times as effective in causing a 50% increase in motor activity at a non-toxic dose.
  • This type of test is well recognized as a useful method for the determination of stimulant activity and is "ice described by P. B. Dews, British Journal of Phat-macology, vol. 8, page 46 (1953), and by G. Chen et al., Journal of Pharmacology and Experimental Therapeutics, vol. 127, page 241 (1959).
  • the valuable pharmaceutical properties of the new compositions of this invention are demonstrated in a variety of test procedures.
  • the anoretic activity of these compositions is readily demonstrated by measuring the marked reduction in food consumption following the administration of the active agents. This indicates a therapeutically desirable method of treating obese conditions.
  • Another test procedure which demonstrates the valuable central nervous system actions of these compositions consists of measuring their ability to counteract a depression induced in mammals by the administration of tetrabenazine hexamate. This test procedure indicates these new compositions show useful antidepressant activity at dose levels which produce little or no untoward reactions or toxic manifestations. These compositions may, therefore, be considered as valuable therapeutic agents for the treatment of depressive states and melancholia.
  • the above compounds are in general, white crystalline solids, only slightly soluble in water. They are insoluble in alkaline solutions. They are basic substances soluble in aqueous mineral acids at room temperature, and in some cases form isolable acid addition salts.
  • the active compounds incorporated in a pharmaceutically acceptable carrier therefor may be used in the form of their free bases or as the non-toxic acid addition salts such as the hydrochloride, sulfate, phosphate, citrate, etc.
  • the new compositions may be administered orally or parenterally and when so administered have been found to be useful therapeutic agents at individual doses ranging from about 25 to 150 milligrams of active ingredient.
  • the dosage regimen can be adjusted to provide the optimum therapeutic response. For example, several doses may be administered daily, or the dose may be proportionately reduced as indicated by the exigencies of the therapeutic situation.
  • compositions and preparations should contain at least 0.25% of the active ingredient.
  • the percentage in the compositions and preparations may, of course, be varied and may conveniently be between 2% and about 60% or more of the weight of the unit.
  • the amount of active ingredient in such therapeutically useful compositions or preparations is such that a suitable dosage will be obtained.
  • Preferred compositions or preparations according to the present invention are prepared in such a manner that a dosage unit form contains between about 25 milligrams and about milligrams of the active compound.
  • Tablets, pills, drages, and the like usually contain the following: a binder such as gum tragacanth, acacia, corn starch or gelatin; 3. disintegrating agent such as corn starch, potato starch, alginic acid, or the like; a lubricant such as stearic acid, magnesium stearate, talc, or the like; and a sweetening agent such as sucrose or saccharin may be added, as Well as a flavoring such as peppermint, oil of Wintergreen, or cherry flavoring.
  • a binder such as gum tragacanth, acacia, corn starch or gelatin
  • disintegrating agent such as corn starch, potato starch, alginic acid, or the like
  • a lubricant such as stearic acid, magnesium stearate, talc, or the like
  • a sweetening agent such as sucrose or saccharin may be added, as Well as a flavoring such as peppermint, oil of Wintergreen, or
  • the active 2-oxazolin-4-ones may be made up into one of the various sustained release forms known to the pharmaceutical art.
  • the therapeuticaly active oxazolin-4-ones may be prepared by several ditferent routes.
  • Z-imino- 5-phenyl-4-oxazolidinone may be readily converted to 3 the active compounds by reaction with secondary amines as illustrated below:
  • This reaction is generally carried out in a solvent such as a lower alkanol, methyl Cellosolve and the like.
  • the temperature range is generally from about 50 to 200 C. It is usually desirable to use an excess of secondary amine to insure a reasonably complete reaction. It is also sometimes desirable to carry out the reaction in an autoclave or other pressure vessel to prevent loss of the secondary amine at the reaction temperature.
  • EXAMPLE 1 Z-dimethylamino-S-phenyl-2-0xaz0lin-4-one A mixture of 8.8 grams of 5-phenyl-2-imino-4-oxazolidino, 9 grams of dimethylamine and 50 milliliters of ethanol is heated in an autoclave at 125 C. for two hours. After cooling, the ethanol is removed by distillation and the residual product is recrystallized from 50 milliliters of ethyl acetate and then from water. 2-dimethylamino 5-pheny1 2 oxazolinl one, MP. 137- 139 C., is thereby obtained.
  • the hydrochloride (prepared with ethanolic hydrogen chloride) melts at 167171 C. (with decomposition).
  • EXAMPLE 2 Z-diethylamino-S-phenyl-2-0xaz0line-4-0ne The procedure of Example 1 is repeated using 4.4 grams of 5-phenyl-Z-imino-4-oxazolidinone and 7.3 grams of diet-hylamine in 25 milliliters of ethanol. The crude product is obtained as an oily syrup and is partially purified by dissolving it in about 25 milliliters of methylene chloride, washing the organic layer with dilute sodium hydroxide solution and recovering the product by distillation of the organic solvent.
  • the hydrochloride (prepared with ethanolic hydrogen chloride) melts at 149-154 C. (with decomposition).
  • EXAMPLE 3 5 -pheny l-2-di-is0-butyIamirz0-2-0xazolin-4-0ne
  • a mixture of 4.4 grams of 5-phenyl-2-imino-4-oxazolidinone and 14 milliliters of di-iso-butylamine in about 13 milliliters of 2 methoxyethanol is "heated at the reflux temperature for 22 hours.
  • the solvent is removed by distillation and the residual oil is Washed ('by decantation) with 50 milliliters of petroleum-ether and then suspended in 25 milliliters of diethyl ether.
  • the solid obtained is unreacted 5-phenyl-2-imino-4-oxazolidinone.
  • EXAMPLE 4 Z-ethylmethylamin0-5-phenyl-2-oxaz0lin-4-0ne
  • a solution of sodium ethoxide prepared by dissolving 0.5 gram of sodium in 20 milliliters of ethanol is treated with 3.8 grams of 5-phenyl-2-methylimino-4-oxo-oxazolidinone ifollowed by 2 milliliters of diethyl sulfate.
  • the solution is refiuxed for about one-half hour and concentrated.
  • the residue is treated with 40 milliliters of water and the product is extracted with methylene chloride.
  • EXAMPLE 5 PREPARATION or PHARMACEUTICAL TABLETS
  • the active ingredient, lactose and corn starch (for mix) are blended together.
  • the corn starch (for paste) is suspended in about 800 milliliters of Water and heated, with stirring, to form a paste. This paste is then used to granulate the mixed powders. Additional water is used, if necessary.
  • the wet granules are passed through a No. 8 hand screen and .dried at 120 F.
  • the dry granules are then passed through a No. 16 screen.
  • the mixture is lubricated with 1% magnesium stearate and compressed into tablets in a suitable tableting machine.
  • the active ingredient, lactose and corn starch (for mix) are blended together.
  • the corn starch (for paste) is suspended in 800 milliliters of water and heated with stirring, to form a paste. This paste is then used to 'granulate the mixed powders. Additional water is used, if necessary.
  • the wet granules are passed through a No. 8 hand screen and dried at F.
  • the dry granules are then passed through a No. 16 screen.
  • the mixture is lubricated with 1% magnesium stearate and compressed into tablets in a suitable tableting machine.
  • R and R are lower alkyl and the non-toxic acid addition salts thereof and a pharmaceutically acceptable carrier therefor.
  • R and R are lower alkyl and the non-toxic acid addition salts thereof and a pharmaceutically acceptable carrier therefor.

Description

United States Patent 3,313,688 METHOD OF PRODUCING CENTRAL NERVOUS SYSTEM SIMULATION AND AN OREXIA Robert Allis Hardy, Jr., Ridgewood, N.J., and Charles Frederick Howell, New City, and Nicanor Quinones Quinones, New York, N.Y., assignors to American Cyanamid Company, Stamford, Conn., a corporation of Maine No Drawing. Filed Mar. 20, 1964, Ser. No. 353,590 12 Claims. (Cl. 167-55) This application is a continuation-in-part of our copending application Ser. No. 35,115 filed June 10, 1960, now abandoned.
This invention rel-ates to novel pharmaceutical compositions having a therapeutic effect on the central nervous system and to methods of treatment involving such compositions.
The present invention comprises a pharmaceutical composition containing as a principal active central nervous system agent a S-phenyl-Z-dialkylamino-2-oxazolin-4-one of the following formula:
| NR Rg wherein R and R are the same or different lower alkyl radicals having from 1 to 4 carbon atoms.
Pharmaceutical compositions containing one or more of the above compounds have been found to be highly useful central nervous system agents. The new compositions of this invention show a mild stimulant action and excellent anoretic action over a wide range of doses and possess distinct advantages over other stimulant drugs such as amphetamines and pipradrol. In addition, the new compositions of this invention are valuable centrally acting therapeutic agents for the management of depression.
Amphetamine and closely related compounds such as methamphetamine have been used as central nervous system stimulants for many years, but numerous undesirable side reactions accompany their administration. For instance, they cause more or less pronounced rise in blood pressure and there is a tendency toward developing tolerance upon continual use. The compositions of the present invention do not have these serious side-effects and thus are markedly superior to the amphetamines. The compositions of this invention also, even at high doses, are freeof the undesirable adrenergic and cardiovascular actions characteristic of the amphetamines. As increasing doses of the amphetamines are given, convulsions are usually observed. The compositions of this invention do not cause convulsions as the doses are increased. They possess a low order of toxicity and a desirably large spread between effective and lethal doses, i.e., a high therapeutic index. They also have a much greater margin of safety than pipradrol which shows a rather narrow range between effective and toxic doses.
Furthermore, the new compositions containing the active drugs are considerably more active than S-phenyl-Z- imino-4-oxo oxazolidine disclosed in United States Patent No. 2,892,753. For example, 2-dimethylamino-S-phenyl- 2 oxazolin 4-one and 2-ethylmethylamino-5-phenyl-2- oxazolin-4-one are approximately nine times as effective in causing a 50% increase in motor activity at a non-toxic dose. This type of test is well recognized as a useful method for the determination of stimulant activity and is "ice described by P. B. Dews, British Journal of Phat-macology, vol. 8, page 46 (1953), and by G. Chen et al., Journal of Pharmacology and Experimental Therapeutics, vol. 127, page 241 (1959).
Additionally, the valuable pharmaceutical properties of the new compositions of this invention are demonstrated in a variety of test procedures. For example the anoretic activity of these compositions is readily demonstrated by measuring the marked reduction in food consumption following the administration of the active agents. This indicates a therapeutically desirable method of treating obese conditions. Another test procedure which demonstrates the valuable central nervous system actions of these compositions consists of measuring their ability to counteract a depression induced in mammals by the administration of tetrabenazine hexamate. This test procedure indicates these new compositions show useful antidepressant activity at dose levels which produce little or no untoward reactions or toxic manifestations. These compositions may, therefore, be considered as valuable therapeutic agents for the treatment of depressive states and melancholia.
The above compounds are in general, white crystalline solids, only slightly soluble in water. They are insoluble in alkaline solutions. They are basic substances soluble in aqueous mineral acids at room temperature, and in some cases form isolable acid addition salts.
The active compounds incorporated in a pharmaceutically acceptable carrier therefor may be used in the form of their free bases or as the non-toxic acid addition salts such as the hydrochloride, sulfate, phosphate, citrate, etc. The new compositions may be administered orally or parenterally and when so administered have been found to be useful therapeutic agents at individual doses ranging from about 25 to 150 milligrams of active ingredient. The dosage regimen can be adjusted to provide the optimum therapeutic response. For example, several doses may be administered daily, or the dose may be proportionately reduced as indicated by the exigencies of the therapeutic situation.
For therapeutic administration the compounds may be incorporated with pharmaceutical excipients and used, for instance, in the form of tablet, drages, capsules, suppositories, liquids to be administered in drops, emulsions, suspensions, syrups, chocolate, candy, and the like. Such compositions and preparations should contain at least 0.25% of the active ingredient. The percentage in the compositions and preparations may, of course, be varied and may conveniently be between 2% and about 60% or more of the weight of the unit. The amount of active ingredient in such therapeutically useful compositions or preparations is such that a suitable dosage will be obtained. Preferred compositions or preparations according to the present invention are prepared in such a manner that a dosage unit form contains between about 25 milligrams and about milligrams of the active compound.
Tablets, pills, drages, and the like usually contain the following: a binder such as gum tragacanth, acacia, corn starch or gelatin; 3. disintegrating agent such as corn starch, potato starch, alginic acid, or the like; a lubricant such as stearic acid, magnesium stearate, talc, or the like; and a sweetening agent such as sucrose or saccharin may be added, as Well as a flavoring such as peppermint, oil of Wintergreen, or cherry flavoring.
In the form of a pamoic acid, alginic acid, tannic acid or other insoluble salt, the active 2-oxazolin-4-ones may be made up into one of the various sustained release forms known to the pharmaceutical art.
The therapeuticaly active oxazolin-4-ones may be prepared by several ditferent routes. For example, Z-imino- 5-phenyl-4-oxazolidinone may be readily converted to 3 the active compounds by reaction with secondary amines as illustrated below:
NH 0 NH 0 IQIH 1 :11.12, where R and R are lower alkyl radicals.
This reaction is generally carried out in a solvent such as a lower alkanol, methyl Cellosolve and the like. The temperature range is generally from about 50 to 200 C. It is usually desirable to use an excess of secondary amine to insure a reasonably complete reaction. It is also sometimes desirable to carry out the reaction in an autoclave or other pressure vessel to prevent loss of the secondary amine at the reaction temperature.
The invention will be described in greater detail in conjunction with the following specific examples.
EXAMPLE 1 Z-dimethylamino-S-phenyl-2-0xaz0lin-4-one A mixture of 8.8 grams of 5-phenyl-2-imino-4-oxazolidino, 9 grams of dimethylamine and 50 milliliters of ethanol is heated in an autoclave at 125 C. for two hours. After cooling, the ethanol is removed by distillation and the residual product is recrystallized from 50 milliliters of ethyl acetate and then from water. 2-dimethylamino 5-pheny1 2 oxazolinl one, MP. 137- 139 C., is thereby obtained.
The hydrochloride (prepared with ethanolic hydrogen chloride) melts at 167171 C. (with decomposition).
EXAMPLE 2 Z-diethylamino-S-phenyl-2-0xaz0line-4-0ne The procedure of Example 1 is repeated using 4.4 grams of 5-phenyl-Z-imino-4-oxazolidinone and 7.3 grams of diet-hylamine in 25 milliliters of ethanol. The crude product is obtained as an oily syrup and is partially purified by dissolving it in about 25 milliliters of methylene chloride, washing the organic layer with dilute sodium hydroxide solution and recovering the product by distillation of the organic solvent. Recrystallization of the product from ether followed by recrystallization from ethyl acetate or aqueous acetone then gives 5-phenyl-2- diethylamino-2-oxazoline-4-one which melts at 7677 C.
The hydrochloride (prepared with ethanolic hydrogen chloride) melts at 149-154 C. (with decomposition).
EXAMPLE 3 5 -pheny l-2-di-is0-butyIamirz0-2-0xazolin-4-0ne A mixture of 4.4 grams of 5-phenyl-2-imino-4-oxazolidinone and 14 milliliters of di-iso-butylamine in about 13 milliliters of 2 methoxyethanol is "heated at the reflux temperature for 22 hours. The solvent is removed by distillation and the residual oil is Washed ('by decantation) with 50 milliliters of petroleum-ether and then suspended in 25 milliliters of diethyl ether. The solid obtained is unreacted 5-phenyl-2-imino-4-oxazolidinone. Concentration of the ethereal filtrate gives the desired product in a crude state. Treatment with an ether solution of anhydrous hydrogen chloride then gives 5-phenyl- 2-di-iso-butylamino-2-oxazolin-4-one hydrochloride.
EXAMPLE 4 Z-ethylmethylamin0-5-phenyl-2-oxaz0lin-4-0ne A solution of sodium ethoxide prepared by dissolving 0.5 gram of sodium in 20 milliliters of ethanol is treated with 3.8 grams of 5-phenyl-2-methylimino-4-oxo-oxazolidinone ifollowed by 2 milliliters of diethyl sulfate. The solution is refiuxed for about one-half hour and concentrated. The residue is treated with 40 milliliters of water and the product is extracted with methylene chloride.
d This solution is Washed with dilute sodium hydroxide solution, dried and concentrated. '2-ethylmethylamino-5- phenyl-2-oxazolin-4-one, M.P. 97 C. is thereby obtained. After two recrystallizations from ethyl acetate the purified product melts at 104107 C.
EXAMPLE 5 PREPARATION or PHARMACEUTICAL TABLETS The active ingredient, lactose and corn starch (for mix) are blended together. The corn starch (for paste) is suspended in about 800 milliliters of Water and heated, with stirring, to form a paste. This paste is then used to granulate the mixed powders. Additional water is used, if necessary. The wet granules are passed through a No. 8 hand screen and .dried at 120 F. The dry granules are then passed through a No. 16 screen. The mixture is lubricated with 1% magnesium stearate and compressed into tablets in a suitable tableting machine.
EXAMPLE 6 PREPARATION or PHARMACEUTICAL TABLETS Per For Tablet 10,000
(g.) Tablets Active ingredient; Z-dimethylamino-5-phenyl'2- oxazolin4-one. 0. 0200 200 Lactose 0. 0800 800 Corn Starch (for mix) 0.0150 150 Corn Starch (for paste) 0.0100 0. 1250 l, 250 Magnesium Stearate (1%) 0. 0013 12. 5 0.1263 1, 262. 5
The active ingredient, lactose and corn starch (for mix) are blended together. The corn starch (for paste) is suspended in 800 milliliters of water and heated with stirring, to form a paste. This paste is then used to 'granulate the mixed powders. Additional water is used, if necessary. The wet granules are passed through a No. 8 hand screen and dried at F. The dry granules are then passed through a No. 16 screen. The mixture is lubricated with 1% magnesium stearate and compressed into tablets in a suitable tableting machine.
We claim:
1. The process of producing therapeutically desirable stimulation of the central nervous system of mammals which comprises administering internally to a mammal in whom a stimulation eflect is desired a composition containing between about 25 and milligrams per dosage unit of a compound selected from the group consisting of 5-pheny1-2-dialkylamino-2-oxazolin-4-ones of the formula:
wherein R and R are lower alkyl and the non-toxic acid addition salts thereof and a pharmaceutically acceptable carrier therefor.
2. The process according to claim 1 in which the compound is selected from the group consisting of Z-dimethylamino-5-phenyl-2-oxazolin-4-one and the non-toxic acid addition salts thereof.
3. The process according to claim 1 in which the compound is selected from the group consisting of Z-ethylmethylamino-5-phenyl-2-oXazolin-4-one and the non-toxic acid addition salts thereof.
4. The process according to claim 1 in which the compound is selected from the group consisting of 2- diethylamino-5phenyl-2-oXazolin-4-one and the non-toxic acid addition salts thereof.
5. The process of producing therapeutically desirable anorexic effects in mammals for control of appetite and treatment of obesity which comprises administering internally to a mammal in whom an anorectic effect is desired a composition containing between about 25 and 150 milligrams per dosage unit of a compound selected from the group consisting of 5-phenyl-2-dialkylamino-Z- oXazolin-4-ones of the formula:
I NR R wherein R and R are lower alkyl and the non-toxic acid addition salts thereof and a pharmaceutically acceptable carrier therefor.
6. The process according to claim 5 in which the compound is selected from the group consisting of Z-dimethylamino-5-phenyl 2-oxazolin-4-one and the non-toxic acid addition salts thereof.
7. The process according to claim 5 in which the compound is selected from the group consisting of Z-ethylmethylamino-5-phenyl-2-oxazolin-4-one and the non-toxic acid addition salts thereof.
8. The process according to claim 5 in which the compound is selected from the group consisting of 2-diethylamino-5-phenyl-2-oxazolin-4-one and the non-toxic acid addition salts thereof.
9. The process of producing a therapeutically desirable effect on the central nervous system of mammals for therapeutic treatment of depression which comprises administering internally to mammals in whom an antidepressant effect is desired a composition containing between about 25 and milligrams per dosage unit of a compound selected from the group consisting of S-phenyl- 2-dialkylamino-2-oXazolin-4-ones of the formula:
CH-C=O i) N 0 IL R1RQ wherein R and R are lower alkyl and the non-toxic acid addition salts thereof and a pharmaceutic-ally acceptable carner therefor.
19. The process according to claim 9 in which the compound is selected from the group consisting of 2- dimethylamino-5+phenyl-2-oxazolin-4-one and the nontoxic acid addition salts thereof.
11. The process according to claim 9 in which the compound is selected from the group consisting of 2- ethylmethylamino-5-phenyl-2-oXazolin-4-0ne and the nontoxic acid addition salts thereof.
12. The process according to claim 9 in which the compound is selected from the group consisting of 2- diethylamino-5-phenyl-2-oXazolin-4-one and the non-toxic acid addition salts thereof.
References Cited by the Examiner UNITED STATES PATENTS 2,687,414 8/1954 Cusic 260243 2,892,753 6/1959 Schmidt 16765 3,029,189 4/1962 Hardy 16765 3,038,896 6/1962 Habicht 260-239 OTHER REFERENCES Aspelund, Chem. A'bstracts 41, 2416 (1947). Lienert, Chem. Abstracts 51, 15805 (1957).
ALBERT T. MEYERS, Primary Examiner. SAM ROSEN, Examiner. STANLEY J. FRIEDMAN, Assistant Examiner.

Claims (1)

1. THE PROCESS OF PRODUCING THERAPEUTICALLY DESIRABLE STIMULATION OF THE CENTRAL NERVOUS SYTEM OF MAMMALS WHICH COMPRISES ADMINISTERING INTERNALLY TO A MAMMAL IN WHOM A STIMULATION EFFECT IS DESIRED TO COMPOSITION CONTAINING BETWEEN ABOUT 25 AND 150 MILLIGRAMS PER DOSAGE UNIT OF A COMPOUND SELECTED FROM THE GROUP CONSISTING OF 5-PHENYL-2-DIALKYLAMINO-2-OXAZOLIN-4-ONES OF THE FORMULA:
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2687414A (en) * 1948-11-26 1954-08-24 Searle & Co Method for producing aromatic aminoalkyl amines
US2892753A (en) * 1957-02-26 1959-06-30 Boehringer Sohn Ingelheim Central nervous system stimulant
US3029189A (en) * 1962-04-10 S-aryl-z-mno-x-qxazolibinones
US3038896A (en) * 1958-05-30 1962-06-12 Cilag Chemie 1-(di-lower alkyl amino lower alkyl thio lower alkyl)-aza-[2, 3:5, 6]-dibenzocycloheptadiene compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3029189A (en) * 1962-04-10 S-aryl-z-mno-x-qxazolibinones
US2687414A (en) * 1948-11-26 1954-08-24 Searle & Co Method for producing aromatic aminoalkyl amines
US2892753A (en) * 1957-02-26 1959-06-30 Boehringer Sohn Ingelheim Central nervous system stimulant
US3038896A (en) * 1958-05-30 1962-06-12 Cilag Chemie 1-(di-lower alkyl amino lower alkyl thio lower alkyl)-aza-[2, 3:5, 6]-dibenzocycloheptadiene compounds

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