DE213155C - - Google Patents
Info
- Publication number
- DE213155C DE213155C DE1907213155D DE213155DA DE213155C DE 213155 C DE213155 C DE 213155C DE 1907213155 D DE1907213155 D DE 1907213155D DE 213155D A DE213155D A DE 213155DA DE 213155 C DE213155 C DE 213155C
- Authority
- DE
- Germany
- Prior art keywords
- acid
- ecm
- water
- arsanilic
- hours
- 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
Links
- 239000002253 acid Substances 0.000 claims description 16
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 229950002705 arsanilic acid Drugs 0.000 claims description 10
- XKNKHVGWJDPIRJ-UHFFFAOYSA-N arsanilic acid Chemical compound NC1=CC=C([As](O)(O)=O)C=C1 XKNKHVGWJDPIRJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000004202 carbamide Substances 0.000 claims description 5
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 claims description 4
- 230000035876 healing Effects 0.000 claims description 4
- 231100000419 toxicity Toxicity 0.000 claims description 4
- 230000001988 toxicity Effects 0.000 claims description 4
- RNXVXXXZBIXZMS-UHFFFAOYSA-N (4-aminophenyl)arsinic acid Chemical class NC1=CC=C([AsH](O)=O)C=C1 RNXVXXXZBIXZMS-UHFFFAOYSA-N 0.000 claims description 3
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 2
- 150000003585 thioureas Chemical class 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 6
- 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 claims 3
- 229960000583 acetic acid Drugs 0.000 claims 3
- 238000001816 cooling Methods 0.000 claims 3
- 239000012362 glacial acetic acid Substances 0.000 claims 3
- 239000000463 material Substances 0.000 claims 3
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 claims 3
- 239000000047 product Substances 0.000 claims 3
- 229910052708 sodium Inorganic materials 0.000 claims 3
- 239000011734 sodium Substances 0.000 claims 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- 238000004090 dissolution Methods 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 claims 2
- DJHGAFSJWGLOIV-UHFFFAOYSA-N Arsenic acid Chemical compound O[As](O)(O)=O DJHGAFSJWGLOIV-UHFFFAOYSA-N 0.000 claims 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 1
- 229940000488 arsenic acid Drugs 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 238000011835 investigation Methods 0.000 claims 1
- JYQQWQJCEUMXQZ-UHFFFAOYSA-N methyl cyanate Chemical compound COC#N JYQQWQJCEUMXQZ-UHFFFAOYSA-N 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- CWHFDTWZHFRTAB-UHFFFAOYSA-N phenyl cyanate Chemical compound N#COC1=CC=CC=C1 CWHFDTWZHFRTAB-UHFFFAOYSA-N 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- GCAKFSUPQDLXIL-UHFFFAOYSA-N potassium rhodium Chemical compound [K].[Rh] GCAKFSUPQDLXIL-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 claims 1
- 239000002244 precipitate Substances 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 150000003672 ureas Chemical class 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000001257 hydrogen Chemical group 0.000 description 1
- 229910052739 hydrogen Chemical group 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/66—Arsenic compounds
- C07F9/70—Organo-arsenic compounds
- C07F9/74—Aromatic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
KAISERLICHES M IMPERIAL M
PATENTAMT.PATENT OFFICE.
PATENTSCHRIFTPATENT LETTERING
- M 213155 KLASSE 12 o. GRUPPE- M 213155 CLASS 12 or GROUP
Patentiert im Deutschen Reiche vom 20. August 1907 ab. Längste Dauer: 4. Oktober 1921.Patented in the German Empire on August 20, 1907. Longest duration: October 4, 1921.
Es wurde gefunden, daß es gelingt, p-Aminophenylarsinsäure, ihre Homologen und Derivate in Harnstoff- und Thioharnstoffabkömmlinge vom Typus:It has been found that p-aminophenylarsinic acid, its homologues and derivatives are successful in urea and thiourea derivatives of the type:
NH-CONH-CO
NH . CSNH. CS
bzw.respectively.
AsO(OHJ2 AsO (OHJ 2
AsO(OH)2 AsO (OH) 2
überzuführen, wobei R ein Alkyl, Aryl oder Wasserstoff bedeutet. Derartige Verbindungen werden erhalten durch Einwirkung von Cyansäure bzw. Sulfocyansäure oder deren Estern auf p-Aminophenylarsinsäure und ihre Abkömmlinge. Die neuen Verbindungen sind gut kristallisierende Substanzen, schwer löslich in kaltem Wasser und verdünnten Mineralsäuren. Durch den Eintritt des Harnstoffrestes erlangen sie eine gegenüber den Ausgangsprodukten stark herabgeminderte Toxizität.convert, where R is an alkyl, aryl or hydrogen. Such compounds are obtained by the action of cyanic acid or sulfocyanic acid or their esters on p-aminophenylarsinic acid and its derivatives. The new compounds are substances that crystallize well and are sparingly soluble in cold water and dilute mineral acids. As a result of the entry of the urea residue, their toxicity is greatly reduced compared to the starting products.
Die Harnstoffderivate der Phenylarsinsäure sind auch weniger toxisch als die schon bekannt gewordenen Acylderivate der p-Aminophenylarsinsäure, welche Eigenschaft ihre Erklärung darin finden kann, daß die Harnstoffderivate im Organismus schwerer einer Spaltung unterliegen als die Acylderivate.The urea derivatives of phenylarsinic acid are also less toxic than those already known acyl derivatives of p-aminophenylarsinic acid, which property explains them can find in it that the urea derivatives in the organism more difficult to split are subject to than the acyl derivatives.
Aus folgenden Vergleichsdaten ergibt sich die 35 The 35th result from the following comparative data
Überlegenheit der neuen Harnstoffderivate. Die Toxizität der Arsanilsäure ist so groß, daß ι ecm einer Lösung ι: 150 auf 20 g Körpergewicht bei Mäusen den Tod in etwa 75 Prozent aller Versuche herbeiführt; Acetylarsanilsäure ist weniger giftig, aber 1 ecm 1: 85 führt jedesmal den Tod herbei, während bei gleicher Konzentration Methylcarbaminoarsanilsäure in keinem Versuch solches Resultat hatte. Auch bei Kaninchen erweist sich die Methylcarbaminoarsanilsäure als halb so giftig als Acetylarsanilsäure. Andererseits sind die Heilfunktionen der Arsanilsäure bei der Maus relativ gering, indem bei der üblichen Prüfungsmethode (vergl. Berliner klinische. Wochenschrift 1907, Chemotherapie, S. 15 des Separatabdrucks), in der die Tiere am ersten Tage nach der Infektion geprüft werden, nur 5 Prozent Heilresultate erzielt wurden. Demgegenüber ist es bei Verwendung der Harnstoffderivate, ζ. Β. des Methylharnstoffs, möglich, auch am zweiten Tage der Infektion, an dem das Blut der Versuchstiere von Millionen von Parasiten durchsetzt ist, noch Heilresultate zu erzielen, und zwar durch eine einzige Injektion. Es gelingt also, ein Tier zu heilen, das sich nur wenige Stunden vor dem Tode befindet.Superiority of the new urea derivatives. The toxicity of arsanilic acid is so great that ι ecm of a solution ι: 150 to 20 g of body weight causes death in mice in about 75 percent of all experiments; Acetylarsanilic acid is less toxic, but leads 1 ecm 1:85 each time causes death, while at the same concentration methylcarbaminoarsanilic acid in never had such a result. Methylcarbaminoarsanilic acid is also found in rabbits than half as toxic as acetylarsanilic acid. On the other hand are the healing functions the arsanilic acid in the mouse is relatively low, as with the usual test method (cf. Berlin clinical. Wochenschrift 1907, Chemotherapie, p. 15 of the separate print), in which the Animals tested on the first day after infection achieved only 5 percent healing results became. In contrast, when using urea derivatives, ζ. Β. of Methylurea, possible even on the second day of infection, on which the blood of the Experimental animals riddled with millions of parasites can still achieve healing results, and through a single injection. So it is possible to heal an animal that only a few can Hours from death.
Auch mit dem Acetylatoxyl kann man am zweiten Tage noch Heilung erzielen, jedoch ist hierfür im allgemeinen eine drei- bis viermalige Wiederholung der Injektion notwendig, undWith the acetylatoxyl one can still achieve a cure on the second day, but it is this generally requires the injection to be repeated three to four times, and
Claims (1)
620 g arsanilsaures Natron werden in 3,61 kaltem Wasser gelöst, 480 g Kaliumcyanat und nach dessen Auflösung 480 ecm Eisessig zuger fügt und 24 Stunden bei gewöhnlicher Temperatur stehen gelassen. Dann wird mit 1560 ecm Salzsäure (spez. Gew. 1,124) angesäuert und durch Reiben der Gefäßwände die Kristallisation eingeleitet. Nach mehrstündigem Stellen wird abgesaugt, mit Wasser salzsäurefrei gewaschen und getrocknet.Carbaminoarsanilic acid.
620 g of arsanilic acid sodium are dissolved in 3.61 cold water, 480 g of potassium cyanate and, after its dissolution, 480 ecm of glacial acetic acid are added and left to stand for 24 hours at normal temperature. Then it is acidified with 1560 ecm hydrochloric acid (specific weight 1.124) and crystallization is initiated by rubbing the walls of the vessel. After standing for several hours, it is filtered off with suction, washed free of hydrochloric acid with water and dried.
Zu 60 g Rhodankalium in x/21 Wasser gibt man 78 ecm Salzsäure (spez. Gew. 1,124) und darauf so lange Arsanilsäure, als diese sich auflöst (etwa 83 g). Nun wird auf dem Wasserbade zum Trocknen gedampft und der Rückstand in derselben Weise noch 2 Stunden erwärmt. Nach dem Erkalten zerreibt man mit 300 ecm Wasser und 150 ecm etwa zehnfach normaler Natronlauge, filtriert vom Ungelösten ab und fällt das Produkt durch Eingießen in überschüssige, verdünnte Salzsäure.Th i oc ar barn ino arsanilic acid.
To 60 g of potassium rhodium in x / 2 l of water are added 78 ecm of hydrochloric acid (specific weight 1.124) and then arsanilic acid as long as it dissolves (about 83 g). It is now evaporated to dryness on the water bath and the residue is heated in the same way for a further 2 hours. After cooling, it is triturated with 300 ecm of water and 150 ecm of about ten times normal sodium hydroxide solution, the undissolved material is filtered off and the product is poured into excess, dilute hydrochloric acid.
Zu 40 g arsanilsaurem Natron, in 240 g Wasser gelöst, werden unter Eiskühlung 14 g Methylcyanat gegeben, darauf 12 Stunden im Eisschrank stehen gelassen. Man säuert dann mit 52 ecm Salzsäure (spez. Gew. 1,12) an und läßt kristallisieren. Weiterbehandlung wie unter Beispiel I.Methylcarbaminoarsanilic acid.
14 g of methyl cyanate are added to 40 g of arsanilic acid sodium, dissolved in 240 g of water, while cooling with ice, and the mixture is then left to stand in the refrigerator for 12 hours. It is then acidified with 52 ecm hydrochloric acid (specific weight 1.12) and allowed to crystallize. Further treatment as in example I.
Zu 31 g arsanilsaurem Natron in 300 g Wasser gibt man unter Eiskühlung 18 g Phenylcyanat und läßt unter häufigem Schütteln 12 Stunden bei niederer Temperatur stehen. Hierauf extrahiert man mit Äther, filtriert vom Ungelösten ab und trennt die ätherische Schicht von der wäßrigen. Beim Ansäuern der letzteren mit 40 ecm Salzsäure (spez. Gew. 1,124) iällt das Produkt aus und wird wie unter Beispiel I bis III weiter behandelt. Eine weiter/3 Menge wird durch Ausziehen des Ungelösten mit warmem Wasser und etwas Soda, Filtrieren und Ansäuern gewonnen.Phenyl carbarn ino a rs anilic acid.
18 g of phenyl cyanate are added to 31 g of arsanilic acid sodium in 300 g of water while cooling with ice and the mixture is left to stand for 12 hours at a low temperature with frequent shaking. It is then extracted with ether, the undissolved material is filtered off and the ethereal layer is separated from the aqueous layer. When the latter is acidified with 40 ecm hydrochloric acid (specific weight 1.124 ), the product precipitates and is treated further as in Examples I to III. Another / 3 amount is obtained by extracting the undissolved material with warm water and a little soda, filtering and acidifying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT43375D AT43375B (en) | 1907-08-19 | 1909-03-15 | Process for the preparation of unsymmetrical urea and thiourea derivatives of p-aminophenylarsinic acid, its homologues and derivatives. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE213155T | 1907-08-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE213155C true DE213155C (en) | 1900-01-01 |
Family
ID=5811764
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1906191548D Expired DE191548C (en) | 1906-10-04 | 1906-10-04 | |
| DE1907213155D Expired DE213155C (en) | 1907-08-19 | 1907-08-19 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1906191548D Expired DE191548C (en) | 1906-10-04 | 1906-10-04 |
Country Status (2)
| Country | Link |
|---|---|
| DE (2) | DE191548C (en) |
| FR (1) | FR392857A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2572730B1 (en) * | 1984-11-02 | 1987-12-11 | Centre Nat Rech Scient | NOVEL ARSENIC DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION, IN PARTICULAR AS PEST CONTROL MEDICINES |
-
1906
- 1906-10-04 DE DE1906191548D patent/DE191548C/de not_active Expired
-
1907
- 1907-08-19 DE DE1907213155D patent/DE213155C/de not_active Expired
-
1908
- 1908-07-31 FR FR392857A patent/FR392857A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE191548C (en) | 1900-01-01 |
| FR392857A (en) | 1908-12-08 |
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