US2774787A - Polyhydrophthalamic acid visceral smooth muscle relaxants - Google Patents
Polyhydrophthalamic acid visceral smooth muscle relaxants Download PDFInfo
- Publication number
- US2774787A US2774787A US378417A US37841753A US2774787A US 2774787 A US2774787 A US 2774787A US 378417 A US378417 A US 378417A US 37841753 A US37841753 A US 37841753A US 2774787 A US2774787 A US 2774787A
- Authority
- US
- United States
- Prior art keywords
- smooth muscle
- acid
- polyhydrophthalamic
- muscle relaxants
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
Definitions
- the present invention relates to therapeutic compounds and more particularly to compounds for relaxing spasm in smooth muscle.
- Spasm of the smooth muscles has a number of disagreeable manifestations depending upon the particular smooth muscle involved. Asthma results from spasm of the bronchi; colitis, ulcer and constipation may result from spasm of the smooth muscle of the pyloric region and gastro-intestinal tract; and dysmenorrhea results from spasm of the smooth muscle of the uterus. In the blood vessels, spasm results in hyptertension and Raynauds disease.
- Another object is to provide a compound which will relax spasm in visceral smooth muscle.
- choline includes a quaternary ammonium group and may also include hydroxy, carboxy, alkyl carboxy, acetyl and other groups.
- the composition of choline is known and frequently several types of choline are present in the system at the same time.
- the antihistamines andlocal anesthetics usually contain a secondary amine group which replaces the quaternary ammonium group of the choline.
- the substitution of the secondary amine group for the quaternary ammonium group affords some relief from the effects of cholines but it does not block or counteract the effect of the quaternary ammonium group itself.
- Various efforts have been made to counteract or block the effect of the quaternary ammonium group but these efforts have been unsuccessful in that they have affected only the hypersecretion effect or because the effect was limited to the area of injection.
- the secondary amine base may have the structure of CH; 0H N N ⁇ ⁇ CH: (J2EE and is combined with the cyclohexene or cyclohexane ring in the form of the following compounds:
- R1 and R2 may be methyl or ethyl and R3 may be hydrogen, or magnesium.
- the compounds described above have various therapeutic uses as described above and may also be used as a bronchial dilation, iantispasmatic and cardiac stimulant.
- the compounds may be administered orally in capsule or tablet form and 50 to 300 milligrams may be administered three or four times daily. Over dosage should be avoided as it may irritate the bronchi and cause coughing.
- That compounds may also be administered in aqueous solution. Dosages of to 300 milligrams in water solution may be injected intramuscularly and dosages of 100 to 500 milligrams in water solution may be injected intravenously. Ordinarily, only one injection a day is glven.
- a .neW composition of matter comprising a compound having the formula in which R1 is selected from the group consisting of methyl and ethyl Rz is selected from the group consisting of methyl 'and ethyl, and R3 is selected from the group consisting of magnesium and hydrogen.
Description
United States Patent POLYHYDROPHTHALAMIC ACID VISCERAL SMOOTH MUSCLE RELAXANTS Charles F. Geschickter, Kensington, and Leonard M. Rice, Baltimore, Md.
N 0 Drawing. Application September 3, 1953, Serial No. 378,417
Claims. (Cl. 260-514) The present invention relates to therapeutic compounds and more particularly to compounds for relaxing spasm in smooth muscle.
This application is a continuation-in-part of application Serial No. 216,274, filed March 17, 1951, now abandoned.
Spasm of the smooth muscles has a number of disagreeable manifestations depending upon the particular smooth muscle involved. Asthma results from spasm of the bronchi; colitis, ulcer and constipation may result from spasm of the smooth muscle of the pyloric region and gastro-intestinal tract; and dysmenorrhea results from spasm of the smooth muscle of the uterus. In the blood vessels, spasm results in hyptertension and Raynauds disease.
Many of these manifestations of smooth muscle spasm are also accompanied by hypersecretion, as is well known in the case of asthma, ulcer, colitis and hayfever.
It is known that smooth muscle spasm is caused by the presence of cholines in the system and one of the objects of the present invention is to provide a therapeutic compound which will neutralize or block the action of these cholines.
Another object is to provide a compound which will relax spasm in visceral smooth muscle.
Basically, choline includes a quaternary ammonium group and may also include hydroxy, carboxy, alkyl carboxy, acetyl and other groups. The composition of choline is known and frequently several types of choline are present in the system at the same time.
The antihistamines andlocal anesthetics usually contain a secondary amine group which replaces the quaternary ammonium group of the choline. The substitution of the secondary amine group for the quaternary ammonium group affords some relief from the effects of cholines but it does not block or counteract the effect of the quaternary ammonium group itself. Various efforts have been made to counteract or block the effect of the quaternary ammonium group but these efforts have been unsuccessful in that they have affected only the hypersecretion effect or because the effect was limited to the area of injection.
It has been found that when a cyclohexene or cyclohexane derivative of a secondary amine base is introduced into the system, complete relief from muscle spasm is obtained.
The secondary amine base may have the structure of CH; 0H N N\ \CH: (J2EE and is combined with the cyclohexene or cyclohexane ring in the form of the following compounds:
in which R1 and R2 may be methyl or ethyl and R3 may be hydrogen, or magnesium.
2,774,787 Patented Dec. 18, 1956 N,N-diethyl-cis-M-tetrahydrophthalamic acid In a 3 liter flask fitted with a dropping funnel, stirrer and reflux condenser was placed 1000 ml. of dry benzene and 304 g. of cis-A -tetrahydrophthalic anhydride. The stirrer was started and 146 g. of diethylamine dissolved in an equal volume of dry benzene was'slowly dropped in. The reaction flask was cooled to moderate the reaction. After all the amine had been added, the mixture was refluxed for 15 minutes. The reaction mixture was allowed to cool and two-thirds of the benzene stripped off. On cooling, the residue set to a crystalline mass. The crystals after filtering and recrystallizing from benzene melted at 104l06 C.
EXAMPLE II Magnesium N,N-diethyl-cis-M-tetrahydrophthalamate The N,N-diethyl-cis-A -tetrahydrophthalamic acid prepared above was reacted in a 50% alcohol water solvent mixture with a 10% excess of magnesium carbonate. After the evolution of gas had subsided the reaction mixture was boiled half an hour to complete the reaction. The mixture was filtered from the excess magnesium carbonate. The filtrate was concentrated to dryness in vacuum to yield the salt as a white, free flowing, water soluble powder.
EXAMPLE III N-diethyl hexahydrophthalamic acid This compound was made as outlined in Example I, using 308 g. of hexahydrophthalic acid. The product melts at 1l1113.
The compounds described above have various therapeutic uses as described above and may also be used as a bronchial dilation, iantispasmatic and cardiac stimulant.
The compounds may be administered orally in capsule or tablet form and 50 to 300 milligrams may be administered three or four times daily. Over dosage should be avoided as it may irritate the bronchi and cause coughing.
That compounds may also be administered in aqueous solution. Dosages of to 300 milligrams in water solution may be injected intramuscularly and dosages of 100 to 500 milligrams in water solution may be injected intravenously. Ordinarily, only one injection a day is glven.
From the foregoing it is apparent that we have attained the objects of our invention and have provided a new therapeutic compound having an anticholine effect. Various changes may be made without departing from the spirit of our invention or the scope of the appended claims.
What is claimed and desired to be secured by United States Letters Patent is:
1. A new composition of matter having the formula R OOORI r 3 in which the ring X is selected from the group consisting of cyclohexene and cyclohexane, R1 is selected from the group consisting of methyl and ethylgroups, R2 is selected from the group consisting of methyl and ethyl groups, and R3 is selected from the group consisting of hydrogen and magnesium.
' 2. A .neW composition of matter comprising a compound having the formula in which R1 is selected from the group consisting of methyl and ethyl Rz is selected from the group consisting of methyl 'and ethyl, and R3 is selected from the group consisting of magnesium and hydrogen.
3. A new composition of matter comprising a compound having the formula References Cited in the file of this patent UNITED STATES PATENTS Reid Mar. 2, 1937 Salzberg Dec. 7, 1939 OTHER REFERENCES Vavon: Bull. Soc. Chim., France 45, 298-9 (1929).
Claims (1)
1. A NEW COMPOSITION OF MATTER HAVING THE FORMULA
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US378417A US2774787A (en) | 1953-09-03 | 1953-09-03 | Polyhydrophthalamic acid visceral smooth muscle relaxants |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US378417A US2774787A (en) | 1953-09-03 | 1953-09-03 | Polyhydrophthalamic acid visceral smooth muscle relaxants |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2774787A true US2774787A (en) | 1956-12-18 |
Family
ID=23493058
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US378417A Expired - Lifetime US2774787A (en) | 1953-09-03 | 1953-09-03 | Polyhydrophthalamic acid visceral smooth muscle relaxants |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2774787A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3028421A (en) * | 1958-03-17 | 1962-04-03 | Diamond Alkali Co | Polyhalogenated tetrahydrophthalamic acid |
| US3031499A (en) * | 1957-05-06 | 1962-04-24 | Glen W Hedrick | Amino acids containing a cyclobutane ring |
| US3083198A (en) * | 1959-07-06 | 1963-03-26 | Merck & Co Inc | Novel 2-alkoxy steroids and processes for preparing the same |
| FR2548180A1 (en) * | 1983-06-14 | 1985-01-04 | Eisai Co Ltd | CARBOXYLIC ACID AMIDES AND THEIR DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2072770A (en) * | 1937-03-02 | Coating composition and drier | ||
| US2101323A (en) * | 1936-06-05 | 1937-12-07 | Du Pont | Monoamides of dicarboxylic acids and process of preparing the same |
-
1953
- 1953-09-03 US US378417A patent/US2774787A/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2072770A (en) * | 1937-03-02 | Coating composition and drier | ||
| US2101323A (en) * | 1936-06-05 | 1937-12-07 | Du Pont | Monoamides of dicarboxylic acids and process of preparing the same |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3031499A (en) * | 1957-05-06 | 1962-04-24 | Glen W Hedrick | Amino acids containing a cyclobutane ring |
| US3028421A (en) * | 1958-03-17 | 1962-04-03 | Diamond Alkali Co | Polyhalogenated tetrahydrophthalamic acid |
| US3083198A (en) * | 1959-07-06 | 1963-03-26 | Merck & Co Inc | Novel 2-alkoxy steroids and processes for preparing the same |
| FR2548180A1 (en) * | 1983-06-14 | 1985-01-04 | Eisai Co Ltd | CARBOXYLIC ACID AMIDES AND THEIR DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS6354321A (en) | Blood sugar lowering agent | |
| US3004031A (en) | Diquaternary salts of papaverino esters | |
| US2774787A (en) | Polyhydrophthalamic acid visceral smooth muscle relaxants | |
| US2866734A (en) | 3-pyridylethyl 2, 4-oxazolidinediones and process | |
| US3781431A (en) | Benzomorphan derivatives as analgesic agents | |
| US3557127A (en) | Substituted cyclohexenes,derivatives thereof and processes for obtaining same | |
| JPS5980657A (en) | 3-phenoxy-1-azetidine carboxamide, manufacture and antispasmodic | |
| US2960441A (en) | Therapeutic compositions of salts of 3, 3-pentamethylene-4-hydroxybutyric acid | |
| US3621100A (en) | Composition and method for producing a tuberculostatic effect | |
| US2878158A (en) | Carbamic acid ester of phenyl isopropyl carbinol | |
| US2280040A (en) | Preparation of nicotinic acid amide | |
| US3789125A (en) | Pharmaceutical compositions containing halo-substituted 2-amino-benzylamine-amides | |
| US3179665A (en) | 9-(n-ethyl and n-propyl piperidyl-3'-methyl)-thioxanthenes | |
| US2899359A (en) | tetrahydrodiazepine | |
| US3131122A (en) | Method of producing analgesia with n-substituted-4-phenyl-4-carbalkoxypiperidines | |
| US2658067A (en) | Substituted carbamic acdj esters | |
| US3655673A (en) | Process for the preparation of oxazolidinone derivatives | |
| US2709171A (en) | Acridone derivatives | |
| US3096244A (en) | Substituted butyric acid amide and analgesia | |
| US3313699A (en) | Compositions for and method of treating the central nervous system | |
| US3313687A (en) | Appetite-suppressing and weight reducing composition | |
| US3335184A (en) | Ortho-diisopropylaminoethoxybutyrophenone and hydrochloride thereof | |
| DE2543821C2 (en) | Certain salts and esters of 1-aminomethyl-1-cycloalkaneacetic acids and medicaments containing these compounds | |
| US2700039A (en) | Penicillin salts of nu-phenylurethanes | |
| SU1447283A3 (en) | Method of producing condensed derivatives of as-triazine |