CH510037A - Diphenylamine derivatives - Google Patents
Diphenylamine derivativesInfo
- Publication number
- CH510037A CH510037A CH238669A CH238669A CH510037A CH 510037 A CH510037 A CH 510037A CH 238669 A CH238669 A CH 238669A CH 238669 A CH238669 A CH 238669A CH 510037 A CH510037 A CH 510037A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- cpds
- aliphatic
- compound
- oxadiazol
- Prior art date
Links
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical class C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 title description 3
- MDTUWBLTRPRXBX-UHFFFAOYSA-N 1,2,4-triazol-3-one Chemical group O=C1N=CN=N1 MDTUWBLTRPRXBX-UHFFFAOYSA-N 0.000 claims abstract description 3
- WTSXVIMLKCKWIW-UHFFFAOYSA-N 3h-1,3,4-oxadiazol-2-one Chemical group O=C1NN=CO1 WTSXVIMLKCKWIW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- -1 aryl-aliphatic Chemical group 0.000 abstract description 3
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract 2
- 125000002723 alicyclic group Chemical group 0.000 abstract 1
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 239000000730 antalgic agent Substances 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 150000003536 tetrazoles Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 2
- 206010053155 Epigastric discomfort Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940102398 methyl anthranilate Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
FR---6873 M (A) Cpds. (I) - where R1 is 1, 3, 4-oxadiazol-2-one, 1, 2, 4-triazol-3-one, tetrazole, or -COOR2; R2 is H or a group hydrolysable to H (aliphatic, aryl-aliphatic, alicyclic, or alicyclic-aliphatic, optionally with hetero-atoms); - (B) Acid-addition salts of cpds. (I), when R2 contains an N-heterocycle; (C) when R2 = H, base-addition salts of cpds. (I). - Anti-inflammatory and analgesic agents.
Description
Procédé pour l'obtention de dérivés de la diphénylamine utilisables en pharmacie La présente invention a pour objet un procédé pour l'obtention de dérivés de la diphénylamine utilisables en pharmacie, représentés par la formule
EMI0001.0000
où R1 représente un reste 1,3,4-oxadiazol-2-one ou 1,2,4- triazol-3-one.
Ce procédé est caractérisé par le fait qu'un composé de la formule
EMI0001.0003
où Z est hydroxy ou amino, est amené à réagir avec du phosgène.
Les composés de la formule XXX peuvent être pré parés en faisant réagir un composé de la formule
EMI0001.0004
où Y est du CN ou COOR2, où R., est un groupe hydro- lysable en hydrogène, avec de l'hydrate d'hydrazine en présence d'un solvant convenable tel que du n.-butanol.
Les composés de la formule XXXI, dans lesquels Y est du COOR , sont eux-mêmes utilisables pharma- ceutiquement, un procédé pour leur obtention étant dé crit dans le brevet suisse N 502307 de la même titu laire.
Il a été constaté que les composés de la formule I possèdent une action valable anti-inflammatoire et anal gésique et que leur administration ne donne pas lieu à de l'irritation gastrique. Ce dernier caractère est particu lièrement important lorsqu'une thérapie à long terme est nécessaire ou désirable.
Les exemples suivants illustrent l'invention et la pré paration des produits de départ <I>Exemple 1:</I> Un mélange d'hydrate d'hydrazine (0,7 g), d'anthrani- late de méthyle N-(2,3,5,6-tétrafluorophényle) et de n.- butanol a été chauffé à reflux pendant trois heures. Le butanol a été distillé sous pression réduite et le résidu solide recristallisé au méthanol pour fournir de l'hydr- azide 2,3,5,6-tétrafluorophényle anthranilique ; p.f. 161-166 C.
<I>2:</I> L'hydrazide (5,3 g) a été dissous dans de l'acide acétique glacial chaud (100 ml), puis la solution a été refroidie à 0 C et enfin traitée à l'aide d'une solution de phosgène dans du toluène (19,2 ml à 12 0/o w/w). Après avoir été laissé reposer à la température am biante pendant toute une nuit, le mélange a été évaporé à sec sous pression réduite et le résidu recristallisé au méthanol pour fournir du o-(2',3',5',6'-tétrafluoroani- lino)-5-phényl-1,3,4-oxadiazol-2-one ; p.f. 252-256 C.
Exemple <I>3:</I> De façon similaire, mais en remplaçant l'hydrazide susmentionné par de l'amidrazide correspondant (c'est- à-dire en utilisant le composé avec un groupe amino en lieu et place du groupe hydroxyle) et en faisant ré agir le mélange à l'aide de phosgène, il a été obtenu du o-(2',3',5',6'-tétrafluoroanilino)-5-phényl-1,2,4-triazol- 3-one.
Process for obtaining derivatives of diphenylamine which can be used in pharmacy The present invention relates to a process for obtaining derivatives of diphenylamine which can be used in pharmacy, represented by the formula
EMI0001.0000
where R1 represents a 1,3,4-oxadiazol-2-one or 1,2,4-triazol-3-one residue.
This process is characterized by the fact that a compound of the formula
EMI0001.0003
where Z is hydroxy or amino, is reacted with phosgene.
Compounds of formula XXX can be prepared by reacting a compound of formula
EMI0001.0004
where Y is CN or COOR2, where R, is a group which can be hydrolysed to hydrogen with hydrazine hydrate in the presence of a suitable solvent such as n.-butanol.
The compounds of formula XXXI, in which Y is COOR, can themselves be used pharmaceutically, a process for their production being described in Swiss Patent No. 502307 of the same holder.
It has been found that the compounds of formula I possess a valid anti-inflammatory and analgesic action and that their administration does not give rise to gastric irritation. The latter character is particularly important when long term therapy is necessary or desirable.
The following examples illustrate the invention and the preparation of the starting materials <I> Example 1: </I> A mixture of hydrazine hydrate (0.7 g), methyl anthranilate N- ( 2,3,5,6-tetrafluorophenyl) and n-butanol was heated under reflux for three hours. The butanol was distilled off under reduced pressure and the solid residue recrystallized from methanol to provide 2,3,5,6-tetrafluorophenyl anthranilic hydrazide; m.p. 161-166 C.
<I> 2: </I> The hydrazide (5.3 g) was dissolved in hot glacial acetic acid (100 ml), then the solution was cooled to 0 C and finally treated with of a solution of phosgene in toluene (19.2 ml at 120 / ow / w). After being left to stand at room temperature overnight, the mixture was evaporated to dryness under reduced pressure and the residue recrystallized from methanol to provide o- (2 ', 3', 5 ', 6'-tetrafluoroani - lino) -5-phenyl-1,3,4-oxadiazol-2-one; m.p. 252-256 C.
Example <I> 3: </I> Similarly, but replacing the aforementioned hydrazide with the corresponding amidrazide (i.e. using the compound with an amino group instead of the hydroxyl group ) and reacting the mixture with phosgene, o- (2 ', 3', 5 ', 6'-tetrafluoroanilino) -5-phenyl-1,2,4-triazol- was obtained 3-one.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2004/66A GB1166861A (en) | 1966-01-15 | 1966-01-15 | New Diphenylamine Derivatives and Compositions containing them |
| CH16267A CH502307A (en) | 1966-01-15 | 1967-01-07 | Process for obtaining diphenylamine derivatives which can be used in pharmacy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH510037A true CH510037A (en) | 1971-07-15 |
Family
ID=25683706
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH238669A CH510037A (en) | 1966-01-15 | 1967-01-07 | Diphenylamine derivatives |
| CH238769A CH510039A (en) | 1966-01-15 | 1967-01-07 | Process for obtaining a derivative of diphenylamine which can be used in pharmacy |
| CH238569A CH521948A (en) | 1966-01-15 | 1967-01-07 | Process for obtaining diphenylamine derivatives which can be used in pharmacy |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH238769A CH510039A (en) | 1966-01-15 | 1967-01-07 | Process for obtaining a derivative of diphenylamine which can be used in pharmacy |
| CH238569A CH521948A (en) | 1966-01-15 | 1967-01-07 | Process for obtaining diphenylamine derivatives which can be used in pharmacy |
Country Status (1)
| Country | Link |
|---|---|
| CH (3) | CH510037A (en) |
-
1967
- 1967-01-07 CH CH238669A patent/CH510037A/en not_active IP Right Cessation
- 1967-01-07 CH CH238769A patent/CH510039A/en not_active IP Right Cessation
- 1967-01-07 CH CH238569A patent/CH521948A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH510039A (en) | 1971-07-15 |
| CH521948A (en) | 1972-04-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |