IL44561A - Salts of 2,6-dioxocyclohexane thiocarboxylic acid 4'-halo-anilides and pharmaceutical compositions thereof - Google Patents
Salts of 2,6-dioxocyclohexane thiocarboxylic acid 4'-halo-anilides and pharmaceutical compositions thereofInfo
- Publication number
- IL44561A IL44561A IL44561A IL4456174A IL44561A IL 44561 A IL44561 A IL 44561A IL 44561 A IL44561 A IL 44561A IL 4456174 A IL4456174 A IL 4456174A IL 44561 A IL44561 A IL 44561A
- Authority
- IL
- Israel
- Prior art keywords
- dioxocyclohexane
- compound
- thiocarboxylic acid
- chloroanilide
- salt
- Prior art date
Links
- LSPXTOOYGWJBNU-UHFFFAOYSA-N cyclohexane-1,3-dione methanethioic S-acid Chemical class C(=S)O.O=C1CC(CCC1)=O LSPXTOOYGWJBNU-UHFFFAOYSA-N 0.000 title claims description 19
- 150000003839 salts Chemical class 0.000 title description 13
- 229940051881 anilide analgesics and antipyretics Drugs 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 title description 3
- 239000000203 mixture Substances 0.000 claims description 28
- KBMXZBWIWSRALH-UHFFFAOYSA-N n-(4-chlorophenyl)-2,6-dioxocyclohexane-1-carbothioamide Chemical compound C1=CC(Cl)=CC=C1NC(=S)C1C(=O)CCCC1=O KBMXZBWIWSRALH-UHFFFAOYSA-N 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 13
- 150000001340 alkali metals Chemical class 0.000 claims description 12
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 10
- 241000233866 Fungi Species 0.000 claims description 9
- 229910052783 alkali metal Inorganic materials 0.000 claims description 9
- -1 alkaline earth metal salt Chemical class 0.000 claims description 8
- 159000000000 sodium salts Chemical class 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 6
- 239000008139 complexing agent Substances 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 229910000272 alkali metal oxide Inorganic materials 0.000 claims description 4
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 4
- 230000001857 anti-mycotic effect Effects 0.000 claims description 3
- 159000000007 calcium salts Chemical class 0.000 claims description 3
- 229910003002 lithium salt Inorganic materials 0.000 claims description 3
- 159000000002 lithium salts Chemical class 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 239000002543 antimycotic Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 claims 1
- 239000000243 solution Substances 0.000 description 24
- 241001465754 Metazoa Species 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000008399 tap water Substances 0.000 description 6
- 235000020679 tap water Nutrition 0.000 description 6
- 208000002474 Tinea Diseases 0.000 description 4
- 206010067409 Trichophytosis Diseases 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000223238 Trichophyton Species 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001342 alkaline earth metals Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000010695 polyglycol Substances 0.000 description 3
- 229920000151 polyglycol Polymers 0.000 description 3
- LDUQUHXCYGDUFJ-UHFFFAOYSA-N 2,6-dioxocyclohexane-1-carboxylic acid Chemical compound OC(=O)C1C(=O)CCCC1=O LDUQUHXCYGDUFJ-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 206010061217 Infestation Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- TZZDOCMFMSDEKY-UHFFFAOYSA-N 2,3-dioxo-n-phenylcyclohexane-1-carboxamide Chemical class C1CCC(=O)C(=O)C1C(=O)NC1=CC=CC=C1 TZZDOCMFMSDEKY-UHFFFAOYSA-N 0.000 description 1
- BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 241001480037 Microsporum Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- LQFDPYJSONNAFO-UHFFFAOYSA-N cyclohexanecarbothioic s-acid Chemical compound SC(=O)C1CCCCC1 LQFDPYJSONNAFO-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
π^κ *m nvnsnn imnyni SALTS OF 2,6-DIOXOCYCLOHEXANE THIOCARBOXYLIC ACID »-HALO-ANILIDES AND PHARMACEUTICAL COMPOSITIONS THEREOF (HOE 73/F 097) The present invention relates to salts of 2,6-dioxocyclo-hexane thiocarboxylic acid ' -halo-anilides and to pharmaceutical compositions thereof.
Over the recent 10 to 15 years, diseases caused by cutaneous fungi in domestic and commercially reared animals have been gaining significance in the economic field. Infested animals are a source of infection not only for other animals but - since man and animal are living closely together nowadays - also, to a considerable extent, for human beings.
This risk of infection is generally even increased by the fact that large numbers of animals are kept on a narrow space which intensifies the contacts between the animals.
Moreover, even in non-agricultural households, the keeping of dogs, cats or other pet animals has had a considerable boom. Just these animals, however, are frequently infested by cutaneous fungi, and demand for adequate compositions for the treatment of small animals has become urgent in veterinary medicine. Whereas commercially reared animals are mainly infested by trichophyton species, the cutaneous fungi infesting small domestic animals are, above all, microsporum species, in addition to the trichophytons.
In recent years, attempts have therefore been made to develop a composition against cutaneous fungi, which can be domesti cally used for all dome-stitr and commercially reared animals and which, in its activity spectrum, comprises the most important cutaneous fungi occurring in the veterinary medicine.
For application purposes, those compositions are especially useful which can be sprayed locally. In addition to a good compatibility with the skin and a good adhesive power, these compositions must be able to penetrate the keratin of the skin and hair in order to reach the seat of the infectants. In spite of the good antimycotic effect evidenced in vitro, many of the medicaments do therefore not assure a satisfactory cure.
The sparingly water-soluble dioxocyclohexane carboxylic acid anilides disclosed in German Offenlegungsschrift No. 2 039 466 have excellent antimycotic properties. For example, 2,6-dioxo-cyclohexane carboxylic acid '-bromoanilide was used as a 1 % solution in diethyl arbonate to treat six fattened bulls infested by a medium strong to heavy trichophytosis. The animals were treated by applying the solution of the composition to the infected sections of the skin by means of a cotton swab twice at a time interval of 3 days.
It appeared that the trichophytosis infestation in all six treated bulls was completely cured within 20 to 25 days after beginning of the treatment. In a following observation period of more than 6 weeks, there was no relapse. The infestation with the cutaneous fungi in an animal, which had been treated with diethyl carbonate only, as well as in the four untreated control animals did not show any clinical change during this time.
In spite of their good activity, these compounds are not very l ee suitable for an application in the veterinary medicine, for they have a solubility which is sufficient for therapeutical purposes only in organic solvents and the handling of those solutions usually involves a certain risk (explosion and fire) .
Drugs used in the veterinary medicine, especially if they are not administered by a veterinarian, require a simple mode of administration. As a composition form for a veterinary composition against cutaneous fungi, there is especially suitable a dry composition which is readily soluble in tap water.
The solubility in water of the alkali metal and alkaline earth metal salts of 2 , 6-dioxocyclohexane carboxylic acid 4'-halo-anilide is, however, not sufficient for therapeutical purposes and, moreover, aqueous solutions of these salts are stable only at a pH-value of more than 12.
It has now been found that odorless solutions which are stable in water can be obtained by dissolving an alkali metal or alkaline earth metal salt of a 2,6-dioxocyclohexane thio- carboxylic acid 4'-halo-anilide of the general formula I in which X stands for a halogen atom and Me for an alkali metal or alkaline earth metal.
The present invention therefore provides physiologically acceptable alkali metal and alkaline earth metal salts of a 2,6-dioxocyclohexane thiocarboxylic acid 4'-halo-anilide of the formula I, a process for the manufacture thereof as well as compositions containing them as active ingredients.
Compounds in which X stands for a chlorine atom are especially preferred.
The above salts are prepared by reacting a 2, 6-dioxocyclohexane thiocarboxylic acid 4'-halo-anilide with an alkali metal or alkaline earth metal hydroxide or a water-soluble carbonate or alcoholate thereof.
The reaction is preferably carried out using equivalent amounts of the two starting compounds. An excess amount of an acid results in an impure product, since the unreacted acid precipitates with the salt. An excess amount of a base, however, has no adverse effect since it remains in solution in the mother liquor after separation of the salt.
When alkali metal and alkaline earth metal hydroxides or carbonates are used, the solvents chosen may be water, lower alcohols (of 1 to 6 carbon atoms), aqueous lower alcohols (of 1 to 6 carbon atoms), aqueous tetrahydrofuran, aqueous dioxan, or aqueous acetone. When alkali metal or alkaline earth metal alcoholates are chosen, anhydrous lower alcohols (of 1 to 6 carbon atoms) or anhydrous inert solvents are used. A solution of an alkali metal or alkaline earth metal hydroxide or a solution or suspension of an alkali metal or alkaline earth metal alcoholate is prepared and reacted with a 2,6-dioxo-cyclohexane thio-carboxylic acid -'-halo-anilide. The salts of the 2 , 6-dioxo-cyclohexane thiocarboxylic acid A-'-halo-anilide have been obtained from their solutions by crystallization, concentration until crystallization or precipitation by addition of suitable solvents, for example acetone.
The acids mentioned as starting compounds are obtained, for example according to German Offenlegungsschrift No. 2,039,466.
The compositions of the invention are preferably dry compositions which are dissolved in tap water to yield a solution suitable for therapeutical application. The active ingredient content of these solutions is preferably about 1 %.
Since the alkaline earth metal salts of a 2,6-dioxocyclo-hexane thiocarboxylic acid 4'-halo-anilide are not so readily soluble in water, it is convenient to add a complexing agent to this dry composition in order to assure a therapeutically effective concentration of the active ingredient in the aqueous solution. The addition of a complexing agent is also required for a dry composition which contains an alkali metal salt, since alkaline earth metal ions which may be present in tap water produce sparingly water-soluble alkaline earth metal salts during the preparation of the aqueous solution, and these salts would then precipitate.
Owing to the poor rheological properties of the salts, the dry compositions contain water-soluble excipients, for example polyglycols, in addition to the active ingredient and the complexing agent.
Subjected to in-vitro tests the compounds of the invention show a very good inhibiting effect on Trichophyton and Micro-sporon species.
This result was also confirmed in the veterinary practice.
The therapeutic tests were performed using the alkali metal and alkaline earth metal salts of 2,6-dioxocyclohexane thio-carboxylic acid 4'-chloroanilide in the form of a dry composition soluble in tap water, to which potassium carbonate, polyglycol 4000 and tetrasodium salt of acetic acid as excipients had been added. The composition was used in a 1 % solution, calculated on active ingredient.
The treatment of a total number of 187 cattle naturally infested by trichophytosis showed the following result: Total of cured upon ... slightly not cattle treatments improved improved cured treated 1Qy 1x 2x 3x 4x 6x ^ 2^ ^ 1^ 84 39 12 5 *) 21 cattle were observed for only 17 days upon the second treatment Successful treatment of dogs and cats demonstrated that the salts of the invention can also be used for the treatment of Microsporon canis as well as trichophytosis diseases in these kinds of animals.
The following Examples serve to illustrate the invention.
E X A M P L E 1; Sodium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloro-anilide 60 Grams of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide were introduced while stirring into a solution of 9.0 g of pure sodium hydroxide in 680 ml of water. Stirring was continued for 15 minutes, the solution was filtered and evaporated at 50°C in vacuo to a small volume. After cooling, off the separated crystals were suction-filtered,/ washed with 35 ml of acetone and dried at 60°C until their weight remained constant. 49.5 Grams of sodium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide of the composition C^^H^-Cl aO S were obtained.
E X A M P L E 2; Potassium salt of 2,6-dioxocyclohexane thiocarboxylic acid '-chloroanilide 6.6 g of potassium hydroxide (85 9 were dissolved in 200 ml of water and 28 g of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloranilide were introduced while stirring into this solution. Stirring was continued for minutes, the solution was filtered and evaporated at 50°C in vacuo to a small volume After cooling, the separated crystals were suction-filtered, off washed with 30 ml of acetone and dried at room temperature. 25 g of potassium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide of the composition C^^H^ ^CIKM^S · 1^0 were obtained.
E X A M P L E 3: Calcium salt of 2,6-dioxocyclohexane thiocarboxylic acid 41-chloroanilide 2.8 g of pure calcium oxide were stirred for 1 hour in 200 ml of water, 28 g of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide were added and stirring was continued for 1 hour. The solution was filtered and evaporated at 50°C in vacuo to a small volume. After cooling, the separated off crystals were suction-filtered,/ washed with 40 ml of acetone and dried over P2°5 * 15 g of calcium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide of the composition (C^H-] ^Cl ^S^Ca were obtained.
E X A M P L E 4; Lithium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4' -chloroanilide 28 Grams of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide were introduced while stirring into a solution of 2#4 g of pure lithium hydroxide in 400 ml of water. The solution was then treated further as disclosed in Example 1. 15.8 g of lithium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4,-chloro-anilide of the composition ClLil^^S were obtained.
E X A M P L E 5: Sodium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4' -chloroanilide 2.3 Grams of sodium were reacted in 80 ml of anhydrous ethanol. To the sodium ethylate solution, 28 g of 2,6-dioxocyclohexane thiocarboxylic acid '-chloroanilide were added and the mixture was refluxed for 5 minutes. The hot solution was filtered, cooled, the crystals were suction-filtered^ off washed with 10 ml of ethanol and dried until their weight remained constant. 22 Grams of sodium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide of the composition C, ^H-j ClNNa02S were obtained.
E X A M P L E 6: Sodium salt of 2,6-dioxocyclohexane thiocarboxylic acid 41-bromoanilide 33 Grams of 2,6-dioxocyclohexane thiocarboxylic acid 4'-bromoanilide were introduced while stirring into a solution of 4.1 g of sodium hydroxide (98 %) in 300 ml of water. Stirring was continued for 30 minutes, the solution was filtered and evaporated at 50°C in vacuo until the crystals began to separate. After addition of 60 ml of acetone, the solution was cooled, the separated crystals were suction-filtered^off washed with 30 ml of acetone and dried at 70°C until their weight remained constant. 23 Grams of sodium salt of 2,6-di cyclohexane thiocarboxylic acid ' -bromoanilide of the composition C1 -^H11Br Na02S were obtained.
E X A M P L E 7; Preparation of a dry composition soluble in tap water The following substances were mixed with each other: potassium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide 10.000 g polyglycol 4000 0.500 g potassium carbonate 0.515 g tetrasodium salt of ethylene-diamine- 1.485 g tetraacetic acid 12.500 g In order to improve the rheological properties, the compacted mixture was -ma e--e-empe-et. on a mill and then passed through a granulating device having a mesh width of 1.5 mm.
The granules obtained could be dissolved in tap water within 2 minutes to give a 2 % solution. !
Claims (6)
1. . An alkali metal and alkaline earth metal salt of a compound of the formula in which X stands for a halogen atom.
2. A compound of claim 1 which is the lithium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide.
3. A compound of claim 1 which is the sodium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4f-chloroanilide
4. A compound of claim 1 which is the potassium salt of 2,6-dioxocyclohexane thiocarboxyl acid 4'-chloroanilide.
5. A compound of claim 1 which is the calcium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-chloroanilide.
6. A compound of claim 1 which is the sodium salt of 2,6-dioxocyclohexane thiocarboxylic acid 4'-bromoanilide. HOE 73/F 097 » A composition which is active against cutaneous fungi and which contains at least one compound as claimed in claim 1 and, where required a complexing agent and/or further excipients. A composition which is active against cutaneous fungi and which contains at least one compound as claimed in claims 2 to 6 and, where required a complexing agent and/or further excipients. A process for the manufacture of a compound as claimed in claim 1, which comprises reacting a 2 , 6-dioxocyclohexane thiocarboxylic acid 4'-halo-anilide with an alkali metal or alkaline earth metal hydroxide or a water-soluble carbonate or alcoholate thereof. An - -e f---fch e--com owi d--a-s--ciainred-irr-cla±m s--an antimycotic ^ge&t, composition of matter containing as active ingredient a compound P. O. Box 33116 Tel-Aviv Attorneys for Applicant - 41, -
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19732317579 DE2317579A1 (en) | 1973-04-07 | 1973-04-07 | SALTS OF 2,6-DIOXOCYCLOHEXANTHIOCARBONIC ACID 4'-HALOGENANILIDES AND THEIR PHARMACEUTICAL PREPARATIONS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL44561A0 IL44561A0 (en) | 1974-06-30 |
| IL44561A true IL44561A (en) | 1977-01-31 |
Family
ID=5877353
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL44561A IL44561A (en) | 1973-04-07 | 1974-04-03 | Salts of 2,6-dioxocyclohexane thiocarboxylic acid 4'-halo-anilides and pharmaceutical compositions thereof |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPS49126810A (en) |
| AT (1) | AT338231B (en) |
| BE (1) | BE813430A (en) |
| CA (1) | CA1019765A (en) |
| CH (1) | CH599146A5 (en) |
| CS (1) | CS191911B2 (en) |
| DD (1) | DD112994A5 (en) |
| DE (1) | DE2317579A1 (en) |
| DK (1) | DK136154C (en) |
| ES (1) | ES424848A1 (en) |
| FR (1) | FR2224161B1 (en) |
| GB (1) | GB1464878A (en) |
| HU (1) | HU168937B (en) |
| IE (1) | IE39358B1 (en) |
| IL (1) | IL44561A (en) |
| IT (1) | IT1043914B (en) |
| KE (1) | KE2802A (en) |
| NL (1) | NL7404495A (en) |
| ZA (1) | ZA742190B (en) |
| ZM (1) | ZM6274A1 (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS551724B2 (en) * | 1974-03-16 | 1980-01-16 |
-
1973
- 1973-04-07 DE DE19732317579 patent/DE2317579A1/en active Pending
-
1974
- 1974-03-28 CA CA196,562A patent/CA1019765A/en not_active Expired
- 1974-04-02 NL NL7404495A patent/NL7404495A/xx not_active Application Discontinuation
- 1974-04-02 ES ES424848A patent/ES424848A1/en not_active Expired
- 1974-04-03 IT IT4264174A patent/IT1043914B/en active
- 1974-04-03 CH CH463874A patent/CH599146A5/xx not_active IP Right Cessation
- 1974-04-03 IL IL44561A patent/IL44561A/en unknown
- 1974-04-04 DD DD17769774A patent/DD112994A5/xx unknown
- 1974-04-05 ZA ZA00742190A patent/ZA742190B/en unknown
- 1974-04-05 IE IE73874A patent/IE39358B1/en unknown
- 1974-04-05 GB GB1524874A patent/GB1464878A/en not_active Expired
- 1974-04-05 AT AT287774A patent/AT338231B/en not_active IP Right Cessation
- 1974-04-05 DK DK190174A patent/DK136154C/en active
- 1974-04-05 CS CS248474A patent/CS191911B2/en unknown
- 1974-04-05 ZM ZM6274A patent/ZM6274A1/en unknown
- 1974-04-06 JP JP3849774A patent/JPS49126810A/ja active Pending
- 1974-04-06 HU HUHO001668 patent/HU168937B/hu unknown
- 1974-04-08 BE BE142954A patent/BE813430A/en unknown
- 1974-04-08 FR FR7412294A patent/FR2224161B1/fr not_active Expired
-
1977
- 1977-11-28 KE KE280277A patent/KE2802A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK136154B (en) | 1977-08-22 |
| ATA287774A (en) | 1976-12-15 |
| BE813430A (en) | 1974-10-08 |
| ZM6274A1 (en) | 1975-01-21 |
| HU168937B (en) | 1976-08-28 |
| GB1464878A (en) | 1977-02-16 |
| IT1043914B (en) | 1980-02-29 |
| DK136154C (en) | 1978-01-23 |
| IL44561A0 (en) | 1974-06-30 |
| FR2224161B1 (en) | 1977-11-04 |
| IE39358L (en) | 1974-10-07 |
| ZA742190B (en) | 1975-04-30 |
| IE39358B1 (en) | 1978-09-27 |
| NL7404495A (en) | 1974-10-09 |
| DD112994A5 (en) | 1975-05-12 |
| JPS49126810A (en) | 1974-12-04 |
| CA1019765A (en) | 1977-10-25 |
| CS191911B2 (en) | 1979-07-31 |
| ES424848A1 (en) | 1976-11-16 |
| FR2224161A1 (en) | 1974-10-31 |
| AT338231B (en) | 1977-08-10 |
| AU6756774A (en) | 1975-10-09 |
| DE2317579A1 (en) | 1974-10-24 |
| CH599146A5 (en) | 1978-05-12 |
| KE2802A (en) | 1978-01-06 |
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