US3213097A - 4-(3'-dimethylaminopropyl)-1-carbalkoxy piperazine derivatives - Google Patents

4-(3'-dimethylaminopropyl)-1-carbalkoxy piperazine derivatives Download PDF

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US3213097A
US3213097A US301194A US30119463A US3213097A US 3213097 A US3213097 A US 3213097A US 301194 A US301194 A US 301194A US 30119463 A US30119463 A US 30119463A US 3213097 A US3213097 A US 3213097A
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dimethylaminopropyl
acid
infection
carbalkoxy
methyl
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US301194A
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Forbes Martin
Howard F Lindh
Andrew S Tomcufcik
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Wyeth Holdings LLC
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American Cyanamid Co
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Priority to US301194A priority patent/US3213097A/en
Priority to BE647594D priority patent/BE647594A/xx
Priority to NL6405988A priority patent/NL6405988A/xx
Priority to ES301524A priority patent/ES301524A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/205—Radicals derived from carbonic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • C07D295/26—Sulfur atoms

Definitions

  • This invention relates to new organic compounds. More particularly, it relates to piperazinecarboxylic acid esters and salts thereof.
  • novel compounds of this invention are the lower alkly esters (particularly methyl and ethyl esters) of 4-(3' dimethylaminopropyl)-l-piperazinecarboxylic acid and the non-toxic acid addition and quaternary salts thereof.
  • the free bases of the compounds of this invention are liquids or low melting solids.
  • The are basic in character and form dibasic acid addition salts with acids such as hydrochloric, hydrobromic, sulfuric, acetic, citric, tartaric, lactic, succinic, maleic, phosphoric, malic, gluconic, ascorbic, 1,1-methylenebis-(2-naphthol-3-carboxylic acid) butane-1,2,3,4-tetracarboxylic acid and the like. It is more convenient to store and use these compounds in the form of the salts rather than as free bases.
  • Lower alkyl 4-( 3'-dimethylaminopropyl)-1- piperazinecarboxylate of the invention may be prepared by reacting 1-carb(lower alkoxy)piperazine with 1-chloro-3- dimethylaminopropane, a commercially available reagent.
  • the compounds of this invention may be prepared from methyl l-piperazinecarboxylate or ethyl 1- piperazinecarboxylate, the latter a commercially available reagent.
  • the reaction is carried out by conventional techniques, usually sodium methoxide, potassium carbonate, sodium bicarbonate or the like, acting as acid binders in refluxing ethanol, fi-methoxyethanol, benzene or the like as solvent.
  • Influenza A PR-8 strain
  • W/V 10% homogenized PR-8 infected mouse lung suspension in sterile brain heart infusion broth
  • Treatment Each dose of 1,600 mg./kg. dissolved in 1 ml. 0.85% NaCl given orally at indicated time and, in the case of more than one dose, at 24 hour intervals thereafter.
  • Treatment 800 mgJkg. subcutaneously at time of infection, at 24 hours and at 48 hours after infection.
  • Infection 0.05 ml. of indicated dilution of the supernate of 10% (W/V) homogenized infected mouse lung suspension in sterile brain heart infusion broth.
  • Infection Intranasal; 0.05 ml. of a 10- dilution in brain heart infusion broth of stock Influenza A (P R-8 strain) virus.
  • Treatment Compound was administered subcutaneously in three doses of 1,600 mgJkg. each dissolved in 0.5 ml. of water, immediately after infection and at 24 and 48 hours after infection. Controls received 0.5 ml. of 0.85% NaCl solution.
  • the compounds of the present invention described may be dispensed in compositions comprising the active ingredient and excipients including a carrier. While the amount of active ingredient to be given daily will depend on many factors such as the size, weight, age, kind and severity of infection, etc. of the Warm blooded animal, a daily intake ranging from to 1000 milligrams per kilogram of body weight will produce good results.
  • the dosage unit may vary from 0.05 to 2 grams and may be in a form to be administered one or more times per day, or in smaller forms for multiple daily, or other more frequent administration. Any of the usual dosage unit forms of pharmaceutical compositions can be useful, for example, tablets, oblets, hard or soft shell capsules, parenteral solutions or suspensions, oral solutions or syrups, etc.
  • Tablets or oblets may include, in addition to active ingredients, any of the following excipients.
  • a binder such as acacia, corn starch, gelatin, or the like.
  • a disintegrating agent such as corn starch, potato starch, alginic acid, or the like.
  • a lubricant such as stearic acid, megnesium stearate, talc or the like.
  • a sweetening agent as saccharin or sucaryl, and/ or a flavoring such as peppermint oil, oil of Wintergreen or orange or cheery flavoring can be used.
  • Capsules may include, in addition to active ingredient, a lubricant and also an inert filler such as lactose, sucrose, corn starch or the like.
  • Solutions usually include an acid such as hydrochloric, citric, tartaric, succinic, maleic, ascorbic, phosphoric or the like, or a suitable buffer thereof.
  • Suspensions include a surfactant such as polyoxyethylene sorbitan monooleate (a complex mixture of polyoxyethylene ethers of mixed partial oleic esters of sorbitol anhydrides); oxyethylated tertiary octylphenol formaldehyde polymer; pisooctylpolyoxyethylenephenol polymers or the like; a suspending agent such as polyethylene glycol 4000 USP (a condensation polymer of ethylene oxide and Water, represented by the formula: HOCH (CH OCH ),,CH OH, wherein n varies from about 70 to 85, the molecular weight being about 4000), carboxy methylecellulose (sodium carboxymethylcellulose, USP, the sodium salt of a carboxymethyl ether of cellulose having a closely controlled number of sodium carb
  • sodium sulfite, monothioglycerol, or the like sodium sulfite, monothioglycerol, or the like; and a preservative such as benzyl alcohol, parabens (methyl and propyl esters of p-hydroxybenzoic acid), or the like.
  • Oral solutions may include a suspending agent or viscosity control such as magnesium aluminum silicate, carboxymethylcellulose or the like as well as a buffer, preservative, etc. Solutions and suspensions may be of the aqueous sugar or sorbitol type. It is also known in pharmaceutical practice to employ a propyleneglycol type solvent for use with drugs.
  • a suspending agent or viscosity control such as magnesium aluminum silicate, carboxymethylcellulose or the like as well as a buffer, preservative, etc.
  • Solutions and suspensions may be of the aqueous sugar or sorbitol type. It is also known in pharmaceutical practice to employ a propyleneglycol type solvent for use with drugs.
  • the precipitated salt is collected by filtration and the filtrate concentrated to a residue.
  • the residue is dissolved in 500 ml. of water, the solution adjusted to pH 13.5 with potassium hydroxide pellets, saturated with potassium carbonate and extracted with 3 x 500 ml. portions of ethyl ether.
  • the combined ether extracts are dried over magnesium sulfate, filtered and the product precipitated with an alcoholic hydrochloric acid.
  • the yield is 113 g. 35.8%, melting point 243248 C.
  • a sample analytically pure had a melting point of 251 253 C.
  • Tlhe compounds of this invention may be dispensed in hard or soft shell capsules.
  • a useful formulation for preparing such capsules is as follows.
  • Methyl 4 (3 dimethylarninopropyl) 1 piperazinecarboxylate dihydrocihloride 25.0 Magnesium stearate 0.1250
  • EXAMPLE IV The compounds of this invention may be dispensed as pharmaceutical tablets or oblets.
  • a useful formulation for preparing tablets or oblets is as follows.
  • each containing 0.5 .g. of active ingredient may be considered to provide an entire single daily dose. Such a tablet might be scored so as to provide fractional daily doses. Alternatively, tablets containing smaller amounts of active ingredient might be prepared for fractional daily or smaller doses.
  • NICHOLAS S. RIZZO Primary Examiner.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

United States Patent O 3,213,097 4-(3-DIMETI-IYLAMINOPROPYL)-l-CARBALKOXY PIPERAZINE DERIVATIVES Martin Forbes, New City, Howard F. Lindh, Monsey, and Andrew S. Tomcufcik, Tappan, N.Y., assignors to American Cyanamid Company, Stamford, Conn., a
corporation of Maine No Drawing. Filed Aug. 9, 1963, Ser. No. 301,194 3 Claims. (Cl. 260-268) This invention relates to new organic compounds. More particularly, it relates to piperazinecarboxylic acid esters and salts thereof.
The novel compounds of this invention are the lower alkly esters (particularly methyl and ethyl esters) of 4-(3' dimethylaminopropyl)-l-piperazinecarboxylic acid and the non-toxic acid addition and quaternary salts thereof.
The free bases of the compounds of this invention are liquids or low melting solids. The are basic in character and form dibasic acid addition salts with acids such as hydrochloric, hydrobromic, sulfuric, acetic, citric, tartaric, lactic, succinic, maleic, phosphoric, malic, gluconic, ascorbic, 1,1-methylenebis-(2-naphthol-3-carboxylic acid) butane-1,2,3,4-tetracarboxylic acid and the like. It is more convenient to store and use these compounds in the form of the salts rather than as free bases.
Lower alkyl 4-( 3'-dimethylaminopropyl)-1- piperazinecarboxylate of the invention may be prepared by reacting 1-carb(lower alkoxy)piperazine with 1-chloro-3- dimethylaminopropane, a commercially available reagent. Specifically the compounds of this invention may be prepared from methyl l-piperazinecarboxylate or ethyl 1- piperazinecarboxylate, the latter a commercially available reagent. The reaction is carried out by conventional techniques, usually sodium methoxide, potassium carbonate, sodium bicarbonate or the like, acting as acid binders in refluxing ethanol, fi-methoxyethanol, benzene or the like as solvent. Ordinarily no effort is made to isolate the product as a free base. Hydrogen chloride is added to the crude product, and the purified product is then recovered, after recrystallization if necessary, as a TABLE I.EFFECT OF TREATMENT WITH ETHYL 4-(3- DIMETHYLAMINOPROPYL)-1-PIPERAZINECARBOXYL- ATE DII'IYDROCHLORIDE ON SURVIVAL OF MICE INFECTED WITH INFLUENZA A (PR-8) Alive/Total (Percent Survivors) on 21st Day After Infection Treatment Each Dose (mg. lkg.)
Treatment Route Subcutaneous Oral Tubing 2 13/100 13 1/20 (5 1/39 (3) Saline Treated Infected Controls 2/100 (2) 8/60 (13) The above results show that at 800 mg./ kg. subcutaneously the mice survival is twelve times that of the controls.
TABLE II.EFFECT OF NUMBER OF DOSES AND SCHED- ULE OF ADMINISTRATION OF ETHYL 4-(3-DIMETIIYL- AMINOPROPYL)-l-PIPE RAZINECARBOXYLATE DIHY- DROCHLO RIDE ON SURVIVAL OF MICE INFECTED WITH INFLUENZA A (PR-8 STRAIN) Time Treatment Initiated Relative to Infection Number of Oral 24 Hours 0 Hour +24 Hours Doses Given 24 Hour Intervals Percent Percent Percent A/T Surv1- A/T Survi- A/T Survivors vors vors None, infected controls 5/80 6 .%/;I=Alive/total on 21st day after infection (total of 2 to 4 experimen s 1 Animals: Taconic Farms male albino mice weighing 205:2 grams.
Infection: Influenza A (PR-8 strain); 0.05 ml. of a 10 dilution of the supernate of a 10% (W/V) homogenized PR-8 infected mouse lung suspension in sterile brain heart infusion broth; intrauasally.
Treatment: Each dose of 1,600 mg./kg. dissolved in 1 ml. 0.85% NaCl given orally at indicated time and, in the case of more than one dose, at 24 hour intervals thereafter.
TABLE III.EFFECT OF TREATMENT WITH ETHYL 4-(3-DIMETHYL- AMINOPROPYL)-1-IIPERAZINECARBOXYLATE DIHYDROCHLORIDE ON SURVIVAL OF MICE INFECTED INTRANASALLY WITH VARIOUS STRAINS OF INFLUENZA VIRUS e A/T=Alive/total on 21st day after infection.
Animals: Taconic Farms male albino mice weighing 205:2 grams.
Treatment: 800 mgJkg. subcutaneously at time of infection, at 24 hours and at 48 hours after infection.
Infection: 0.05 ml. of indicated dilution of the supernate of 10% (W/V) homogenized infected mouse lung suspension in sterile brain heart infusion broth.
1 Significant difference at 5% level.
2 Significant difference at 1% level.
TABLE IV.EFFECT OF METHYL 4-(3-DIMETHYLAMINO- PROPYL)-1-PIPERAZINEOARBOXYLATE DIHYDRO- CHLORIDE ON SURVIVAL OF MICE INFECTED WITH INFLUENZA VIRUS Animals: Taconic Farms male white mice, 19-25 grams body weight.
Infection: Intranasal; 0.05 ml. of a 10- dilution in brain heart infusion broth of stock Influenza A (P R-8 strain) virus.
Treatment: Compound was administered subcutaneously in three doses of 1,600 mgJkg. each dissolved in 0.5 ml. of water, immediately after infection and at 24 and 48 hours after infection. Controls received 0.5 ml. of 0.85% NaCl solution.
The combined tests show that 8 times as many mice survived when given the drug over survival of controls.
The compounds of the present invention described may be dispensed in compositions comprising the active ingredient and excipients including a carrier. While the amount of active ingredient to be given daily will depend on many factors such as the size, weight, age, kind and severity of infection, etc. of the Warm blooded animal, a daily intake ranging from to 1000 milligrams per kilogram of body weight will produce good results. The dosage unit may vary from 0.05 to 2 grams and may be in a form to be administered one or more times per day, or in smaller forms for multiple daily, or other more frequent administration. Any of the usual dosage unit forms of pharmaceutical compositions can be useful, for example, tablets, oblets, hard or soft shell capsules, parenteral solutions or suspensions, oral solutions or syrups, etc.
Tablets or oblets may include, in addition to active ingredients, any of the following excipients. A binder such as acacia, corn starch, gelatin, or the like. A disintegrating agent such as corn starch, potato starch, alginic acid, or the like. A lubricant such as stearic acid, megnesium stearate, talc or the like. Also, a sweetening agent as saccharin or sucaryl, and/ or a flavoring such as peppermint oil, oil of Wintergreen or orange or cheery flavoring can be used.
Capsules may include, in addition to active ingredient, a lubricant and also an inert filler such as lactose, sucrose, corn starch or the like.
Solutions, usually include an acid such as hydrochloric, citric, tartaric, succinic, maleic, ascorbic, phosphoric or the like, or a suitable buffer thereof. Suspensions include a surfactant such as polyoxyethylene sorbitan monooleate (a complex mixture of polyoxyethylene ethers of mixed partial oleic esters of sorbitol anhydrides); oxyethylated tertiary octylphenol formaldehyde polymer; pisooctylpolyoxyethylenephenol polymers or the like; a suspending agent such as polyethylene glycol 4000 USP (a condensation polymer of ethylene oxide and Water, represented by the formula: HOCH (CH OCH ),,CH OH, wherein n varies from about 70 to 85, the molecular weight being about 4000), carboxy methylecellulose (sodium carboxymethylcellulose, USP, the sodium salt of a carboxymethyl ether of cellulose having a closely controlled number of sodium carboxymethyl (CH COONa) groups introduced into the cellulose molecule to bring about solubility in water); methylcellulose (cellulose methyl ether prepared from wood pulp or chemical cotton by treatment with alkali and methylation of the alkali cellulose with methyl chloride), and the like; and a buffer such as a phosphate, citrate, or tartrate buffer. Both solutions and suspensions may include a stabilizer such as disodium salt of ethylene-diarninetetraacetic acid,
sodium sulfite, monothioglycerol, or the like; and a preservative such as benzyl alcohol, parabens (methyl and propyl esters of p-hydroxybenzoic acid), or the like.
Oral solutions may include a suspending agent or viscosity control such as magnesium aluminum silicate, carboxymethylcellulose or the like as well as a buffer, preservative, etc. Solutions and suspensions may be of the aqueous sugar or sorbitol type. It is also known in pharmaceutical practice to employ a propyleneglycol type solvent for use with drugs.
The invention is further illustrated by means of the following examples.
EXAMPLE I Preparation of ethyl N-(3'-dimethylaminopropyl)-1- piperazinecarboxylate dihydrochloride To a round bottom flask is added 420 g. (2.66 moles) of 3-dimethylaminopropylchloride'HCl and 158 g. (1.0 mole) of ethyl l-piperazinecarboxylate in 1 liter of ethanol The reaction mixture is heated in refluxing conditions and a solution of 217 g. (4.03 moles) of sodium methylate in 2 liters of ethanol is added over a period of 30 minutes. The mixture is heated under refluxing conditions for an additional hour and cooled to 10-20" C. The precipitated salt is collected by filtration and the filtrate concentrated to a residue. The residue is dissolved in 500 ml. of water, the solution adjusted to pH 13.5 with potassium hydroxide pellets, saturated with potassium carbonate and extracted with 3 x 500 ml. portions of ethyl ether. The combined ether extracts are dried over magnesium sulfate, filtered and the product precipitated with an alcoholic hydrochloric acid. The yield is 113 g. 35.8%, melting point 243248 C. A sample analytically pure had a melting point of 251 253 C.
EXAMPLE II Preparation of methyl 4-(3-dimethylamin0propyl)-1- piperazinecarboxylate dihydrochloride To a Solution of 20.7 g. (50 mmoles) of 1(3- dimethylaminopropyl)-piperazine with 150 ml. 1 N sodium hydroxide is added, simultaneously, 7.1 g. (75 mmoles) of methyl chloroformate and 112.5 ml. of 2 N sodium hydroxide. After stirring for one hour, solid potassium carbonate is added, to near saturation, and the mixture is extracted with two 250 ml. portions of chloroform. The extract is dried over anhydrous magnesium sulfate, and stripped of solvent at the Water pump. A solution of the residual oil in 25 alcohol is heated with 25 ml. of saturated alcoholic hydrogen chloride. The White solid (14.2 g.) is recrystallized twice from methanol, giving 8.3 g. (55%) of analytically pure product, melting point 237 C., dec.
EXAMPLE III Tlhe compounds of this invention may be dispensed in hard or soft shell capsules. A useful formulation for preparing such capsules is as follows.
G. Methyl 4 =(3 dimethylarninopropyl) 1 piperazinecarboxylate dihydrocihloride 25.0 Magnesium stearate 0.1250
Mix thoroughly and dispense in 50 capsules.
EXAMPLE IV The compounds of this invention may be dispensed as pharmaceutical tablets or oblets. A useful formulation for preparing tablets or oblets is as follows.
For tablet, g.
Ethyl 4-(3-dimethy1aminopropyl)-1-piperazinecarboxy late dihyd-rochloride 50.0 Corn starch 2.0 Methyl cellulose (viscosity, 400 cps.) 0.50
Magnesium stearate, 1% 0.525 Mix thoroughly and dispense as tablets.
The above tablets each containing 0.5 .g. of active ingredient may be considered to provide an entire single daily dose. Such a tablet might be scored so as to provide fractional daily doses. Alternatively, tablets containing smaller amounts of active ingredient might be prepared for fractional daily or smaller doses.
We claim:
.1. A lower alkyl ester of 4-(3'-dimethylaminopropyl)- l-piperazinecarboxyl-ic acid and non-toxic acid addition and quaternary salts thereof.
2. The compound methyl 4-(3-dimethyl=aminopropyl)- 1-pipe-nazinecarboxylate.
3. The compound ethyl 4 (3'-dimethylaminopropyl)-i1- piperazin'ecarboxylate.
References Cited by the Examiner UNITED STATES PATENTS 2,541,584 2/51 Jacoby 260268 2,710,823 6/55 Katz 1'6765.2
2,710,824 6/55 Katz 167- 652 2,753,350 7/56 Hasselstrom 260268 2,794,804 6/ 57 Kushner et all 260268 3,015,657 1/62 Gesc-hickter et a1. 260-268 FOREIGN PATENTS 547,981 10/ 57' Canada.
OTHER REFERENCES Harfenist: Journal American Ohemical Society, vol. 79, pp. 2211-15 (1957) Stewart et ral.: Journal Organic Chemistry, volume 13, \pages 134-143, page 142 relied on (1948).
NICHOLAS S. RIZZO, Primary Examiner.

Claims (1)

1. A LOWER ALKYL ESTER OF 4-(3''-DIMETHYLAMINOPROPYL)1-PIPERAZINECARBOXYLIC ACID AND NON-TOXIC ACID ADDITION AND QUATERNARY SALTS THEREOF.
US301194A 1963-06-28 1963-08-09 4-(3'-dimethylaminopropyl)-1-carbalkoxy piperazine derivatives Expired - Lifetime US3213097A (en)

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US291282A US3274054A (en) 1963-06-28 1963-06-28 Antiviral compositions and method of administration
US301194A US3213097A (en) 1963-06-28 1963-08-09 4-(3'-dimethylaminopropyl)-1-carbalkoxy piperazine derivatives
BE647594D BE647594A (en) 1963-06-28 1964-05-06
NL6405988A NL6405988A (en) 1963-06-28 1964-05-28
ES301524A ES301524A1 (en) 1963-06-28 1964-06-27 Procedure for the preparation of antivirus compositions in a unit dosage form (Machine-translation by Google Translate, not legally binding)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3331842A (en) * 1963-07-24 1967-07-18 Delalande Michel Carbalkyloxy-piperazine derivatives
US4977156A (en) * 1988-07-26 1990-12-11 The Dow Chemical Company Amino piperazine esters showing biocidal activity

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3458515A (en) * 1966-07-21 1969-07-29 American Home Prod Piperazine substituted pyrroles
FR2081564A1 (en) * 1970-03-05 1971-12-10 Delalande Sa N-amino carbonyl-piperazines analgesics - antiinflammatories ,hypotensives and spasmolytics

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2541584A (en) * 1947-06-11 1951-02-13 Nat Aluminate Corp N-acylated piperazines
US2710823A (en) * 1952-09-17 1955-06-14 Schenley Ind Inc Fungicidal compounds
US2710824A (en) * 1952-09-17 1955-06-14 Schenley Ind Inc Fungicidal compounds
US2753350A (en) * 1951-11-01 1956-07-03 Hasselstrom Torsten Pungent-tasting pentavalent piperazine diacid salts
US2794804A (en) * 1955-03-24 1957-06-04 American Cyanamid Co Substituted piperazines and method of preparing the same
CA547981A (en) * 1957-10-29 L. Bach Frederick Substituted piperazines and method of preparing the same
US3015657A (en) * 1959-05-28 1962-01-02 Charles F Geschickter 1-carbalkoxy-4-(aminoalkanol) piperazines

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA547981A (en) * 1957-10-29 L. Bach Frederick Substituted piperazines and method of preparing the same
US2541584A (en) * 1947-06-11 1951-02-13 Nat Aluminate Corp N-acylated piperazines
US2753350A (en) * 1951-11-01 1956-07-03 Hasselstrom Torsten Pungent-tasting pentavalent piperazine diacid salts
US2710823A (en) * 1952-09-17 1955-06-14 Schenley Ind Inc Fungicidal compounds
US2710824A (en) * 1952-09-17 1955-06-14 Schenley Ind Inc Fungicidal compounds
US2794804A (en) * 1955-03-24 1957-06-04 American Cyanamid Co Substituted piperazines and method of preparing the same
US3015657A (en) * 1959-05-28 1962-01-02 Charles F Geschickter 1-carbalkoxy-4-(aminoalkanol) piperazines

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3331842A (en) * 1963-07-24 1967-07-18 Delalande Michel Carbalkyloxy-piperazine derivatives
US4977156A (en) * 1988-07-26 1990-12-11 The Dow Chemical Company Amino piperazine esters showing biocidal activity

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