DE1445673B - Phenylamino-pyridines - Google Patents

Description

Ο, Ν-Ι

(Π)

in which R ^{5 has} the above meaning and R ² ', R ³ ' and R ⁴ 'have the same meaning as R ² , R ³ and R ⁴ and can also each mean a nitro group, this nitro group (s) is reduced to an amino group, in one of the pyridine core and optionally in the 2-part sec. Amino group introduces either an aliphatic acyl radical having 1 to 6 carbon atoms or a carbalkoxy radical having 1 to 6 carbon atoms, which can optionally be substituted by a morpholino radical, and the free base thus obtained is optionally converted into an acid addition salt.

3. The method according to claim 2, characterized in that for the case where R ¹ is intended to mean a morpholino or a morpholinoalkoxy group, the amino group to be substituted is reacted with an aromatic or araliphatic halocarbonic acid half ester and then with morpholine or a morpholinoalkanol.

The invention relates to phenylaminopyridines of the general formula I.

Ri_C0 -

in which R ^{1 is} an alkyl radical having 1 to 5 carbon

in which R ^{5 has} the above meaning and R ² ', R ³ ' and R ⁴ 'have the same meaning as R ² , R ³ and R ⁴ and can also each mean a nitro group, this nitro group (s) is reduced to an amino group, in one of the pyridine core and optionally in the 2-part sec. Amino group introduces either an aliphatic acyl radical with 1 to 6 carbon atoms or a carbalkoxy radical with 1 to 6 carbon atoms, which can optionally be substituted by a morpholino radical, and the free base thus obtained is optionally converted into an acid addition salt.
In the event that R ^x is intended to mean a morpholino or a morpholinoalkoxy group, the amino group to be substituted is reacted with an aromatic or araliphatic halocarbonic acid half-ester and then with morpholine or a morpholinoalkanol.

The hydrogenation of the nitro groups is preferably carried out in the presence of a catalyst, for example Raney nickel, and at about 70 ° C. and at a pressure of about 20 to 30 atmospheres. In addition to Raney nickel, the following catalysts can also be used: Palladium black or palladium or palladium hydroxide on a carrier material such as barium sulfate or calcium carbonate. The reduction can also be carried out with zinc / hydrochloric acid, tin / hydrochloric acid, tin (II) chloride / hydrochloric acid or iron / hydrochloric acid or salts of hydrogen sulfide in alcohol / water at about 70 to about 120 ° C or with activated aluminum in aqueous ether at 20 to 40 ⁰ C can be carried out. . "

For the partial acylation of the substituted amino groups, for example, the corresponding acid halide or acid anhydride is used. Expediently, temperatures below 70 ^° C., preferably temperatures between about 30 and about 50 ^° C., are maintained here. The reaction times are generally less than 1 hour. However, the acylation can also be carried out using appropriate esters. In this case, higher temperatures, for example from 150 to 180 ° C., are maintained.

The acylation of the central nitrogen atom, which is preferably carried out subsequently, is also reacted with acid halides or acid anhydrides, but at temperatures above about 7O ⁰ C, preferably

3 4

between about 80 and about 120 ° C. Here- example 6

with longer reaction times, for example of 2- (3-trifluoromethylphenylamino) -5-acetamino-

3 hours, required. pyridine

The new compounds have valuable pharmaceutical

ecological properties. They are characterized by a .5 2 - (3 - trifluoromethylphenylamino) - 5 - nitro - pyridine high anti-inflammatory effect. is hydrogenated analogously to Example 1 with Raney nickel and

worked up. The free base boils at 0.5 torr at 190 to 192 ° C. Together with maleic acid, it forms a crystalline

Example 1 lines salt, which after recrystallization from iso-

^ -Phenylamino-S-acetamino-pyridine ip propanol at 115 ⁰ C melts.

101 g 2- (3-trifluoromethylphenylamino) -5-amino-

142 g of 2-phenylamino-5-nitro-pyridine in pyridine are reacted analogously to Example 1 with 38 ml of acetic anhydride in 200 ml of Ben-600 ml of methanol in the presence of 30 g of Raney nickel. The reaction product is ^{hydrogenated at 70 °} C. and 20 to 30 atmospheres. After the removal is recrystallized from ethanol. Mp. 196 ° C.
evaporating the solvent, the residue in the ^ 5

Vacuum distilled. The base goes between at 0.5 torr ^; For S ρ ie 1 7

190 and 200 ° C above and has after the recrystalline 2- (3-trifluoromethylphenylamino) -5-propionyl-

sieren from isopropanol a melting point of 136 C. aminopyridine

18.5 g of 2-phenylamino-5-aminopyridine are in

40 ml of Diöxan at 40 to 50 ⁰ C with 9.5 ml of acetic anhydride 20 80 g of 2- (3-trifluoromethylphenylamirio) -5-amino reacted. After a short time, the 2-phenylamino-pyridine precipitates with 41 g of propionic anhydride analogously to 5-acetaminopyridine. It is converted from dioxane to Example 6 in 200 mJ benzene. The raw procrystallizes. Mp. 177 ⁰ C. domestic product is recrystallized from isopropanol. Mp. 166 ⁰ C.

t, .., “ ² 5 examples

Example 2

. _ ,,,. . . ,. . ... 2- (3-trifluoromethylphenylamino) -5-carbethoxy-

2-phenylammo-5-propionylamineb-pyndine aminopyridine

56 g of 2-phenylamino-5-aminopyridine are analogous to 65 g of 2- (3-trifluoromethylphenylamino) -5-amino-

Example 1 with 39 g of propionic anhydride in 10Ö ml of 30 pyridine are mixed with 24.5 ml of ethyl chloroformic acid dioxane implemented. The reaction product is made from ester in 200 ml of acetone and 30 ml of pyridine analogously to ethanol recrystallized. Mp. 172 ° C. Game 3 implemented. The reaction product will be off

Recrystallized ethanol. Mp. 175 ° C.

Example ³ 35 Example 9

Z-phenylamino-S-carbäthoxyamino-pyridine 2- (N-3-trifluoromethylphenyl-N-propionylamino) -

"" ■ "", ■ · ',. r. . ..- j 5-propionylamino-pyridine:

9.3 g of 2-phenylamino-5-ammo-pyndin are in

30 ml of dioxane and 6 ml of pyridine with 4.8 ml of chloramine- 15 g of 2- (3-trirluoromethylphenylamino) -5-propioriyl-

ethyl acetate at 40 to 50 ⁰ C implemented. After 40 ämino-pyridine with 6.5 g of propionic anhydride

For 1 hour, the solvent is distilled off in vacuo in 50 ml of dioxane, reacted analogously to Example 4, and increased

The residue was dissolved in chloroform and worked with. Das'Reaktionsprodukt is from a

Water washed. The chloroform is then recrystallized from the ethanol-gasoline mixture. Melting point 118 ^° C. and the residue was recrystallized from ethanol. M.p. 141 ^° C. 45 Example 10

Example 4 2- [N-Carbethoxy- (3-trifluofniethylphenylamino)] -

".. _T _. ,. _T. ,. ν,. , 5-carbethoxyamino-pyridine

2- (N-phenyl-N-propionylamino) -5-propionyl-

ämiho-pyridiri 23.5 g 2 - (3 - trifluoromethylphenylamino) - 5 - carb-

50 ethoxyamino-pyridine, 9 ml ethyl chloroformic acid

12 g of 2-phenylamino-5-propionylamino-pyridine are ester and 16 g of potassium carbonate in 100 nil of

with 7.2 g of propionic anhydride in 40 ml of dioxane ethyl ketone for 3 hours, boiled. The reaction pro-

Cooked for 5 hours Jang. After the product has been distilled off, a benzene-gasoline mixture is converted

Dioxane, the residue is dissolved in benzene and crystallized with. Mp. 100 to 102 ⁰ C.
Washed dilute sodium hydroxide solution. The benzene turns 55

distilled off, and the reaction product from a Bbispielll

Recrystallized ethanol-gasoline mixture. Mp. 124 ° C. 2- (3-Trifluoromethylphenylamino) -5-morpholino-

¹ · carbonylamino-pyridine

Example 5 _{6o 2} 0 g 2- (3-trifluoromethylphenylamino) -5-carbeth-

2- (N-Carbethoxy-phenylamino) -5-carbethoxy- "" oxyamino-pyridine, prepared analogously to Example 3 from

ämiho-pyridiri '"-" 2- (3-trifluoromethylphenylammo) -5-aminopyridine and

Ethyl chloroformate, 9 g of morpho

20 g of 2-phenylamino-S-carbäthoxyamino-pyridine, lin at 140 ⁰ C implemented. After 30 minutes, the 7.5 ml of ethyl chloroformate and 13.5 g of potassium melt are dissolved in benzene and washed with dilute sodium carbonate in 150 ml of benzene for 3 hours. The benzene is distilled off and the boiled and the reaction product is recrystallized from an etha residue from an ethane oil-gasoline mixture umnol-gasoline mixture. Mp. 92 ° C. crystallized. Mp. 84 to 86 ⁰ C.

5 6

Example 12 Example 17

2- (3-trifluoromethylphenylamino) -5-morpholino- 2- (4-fluorophenylamino) -5-carbethoxyamino-

ethoxycarbonylamino-pyridine pyridine

15 g of 2- (2-trifluoromethylphenylamino) -5-carbäth- 5 2- (4-fluorophenylamino) -5-aminopyridine is made from

oxyamino-pyridine are mixed with 10.5 g of morpholino- 2- (4-fluorophenylamino) -5-nitro-pyridine as in the example

Ethanol, as described in Example 11, reacted and 14 produced by catalytic reduction. she will

worked up. The hydrochloride is recrystallized from isopropanol from alcohol / gasoline. M.p. 141 ^° C; Out-

recrystallized. Mp. 200 ⁰ C. yield 90%.

ιό 31 g of 2- (4-fluorophenylamino) -5-aminopyridine are

. . the one in 100 ml of acetone at 25 to 30 ° C with 14.5 ml

e ι s ρ ι e j ethyl chloroformate implemented. It will be like in the

2- (4-Pentyloxyphenylamino) -5-acetaminopyridine Example 14 worked up. M.p. 138 ^° C; Yield: 20 g.

2- (4-Pentyloxyphenylamino) -5-nitro-pyridine is 15 Example 18

hydrogenated analogously to Example 1 with Raney nickel and raised ₂ - (2-methyl-5-chlorophenylamino) -5- _C arbäthoxy-

is working. The base boils at 0.5 Torr between 225 and ^{v J} amino-pyridine

26 g of 2- (4-pentyloxyphenylamino) -5-aminopyridine Reduce 2- (2-methyl-5-chlorophenylamino) -

are 5-nitro-pyridine as in Example 14 with 9 ml of acetic anhydride in 100 ml of benzene analogously. The reaction product is made from duct is distilled in vacuo. _{Bp 0.15} 190 recrystallized to ethanol. M.p. 167 ° C. 195 ⁰ C; Yield: 92%. ' ^

This compound is analogous to Example 14 with chlorine C \

. . ethyl formate reacted. The reaction pro-

_{For example,} 14 25 product is recrystallized from ethanol. Mp 123 ° C;

2- (2-methylphenylamino) -5-carbethoxyamino yield: 43%

pyridine

Example 19

, ¹²⁶ g 2- (2-methylphenylamino) _-5-nitro-P yridin advertising ^ amino-S-oO-trifluoromethyl-carbäthoxyamino

the slurried in 1.21 methanol and m counter-nhenvlaminoVovridin

_: Waist of 13 g of Raney nickel at 6O ⁰ C and 50 atm in pnenylamino; pyridine

Hydrogenated autoclave. After the catalyst has been filtered off with suction, 115 g (0.5 mol) of 2-amino-3-nitro-6- (3-trifluoromethyl-

the filtrate is evaporated and the residue in the phenylamino) pyridine in 500 ml of dioxane is distilled in vacuo. _{B.p. 0.12} 178 to 185 ° C; Yield: 12 g Pd / activated carbon (10%) with the addition of 60 g Na-95 g. 35 trium sulfate at 20 atmospheres and 50 ⁰ C hydrogenated. After

20 g of 2- (2-methylphenylamino) -5-aminopyridine are suctioned off, 100 ml of ether and gasoline are added until the cloudiness begins in 100 ml of acetone in the presence of 8 ml of pyridine. The base crystallizes out. at 25 ^° C. with 9.6 ml of ethyl chloroformate. It is quickly suctioned off (sensitive to air). Yield: set. The acetone is evaporated off, the residue 70 g. By adding isopropanolic hydrochloric acid, the mixture is taken up with benzene and the hydronic liquor is shaken with dilute sodium hydroxide solution of the amine in ethanol. The benzene solution turns out to be chloride. Mp. 300 ° C (decomposition), evaporated, the residue is removed from ethanol / gasoline to 15 g of 2,3-diamino-6- (3-trifluoromethylphenylami-

recrystallized '. Mp 128 ° C; Yield: 11 g. no) pyridine in 100 ml of dioxane is added to 20 g of chlorine

ethyl formate. The reaction product kri- ₍ <,

_n . . . 45 stalled out. It is sucked off and twice from Was- v_

Examples _{sef to} k _r j _s tallisiert. Mp 185-192 ° C; Yield: 8 g.

2- (2,3-dimethylphenylamino) -5-carbethoxyamino-

pyridine example 20

-m / i -M _1n . , .Uli. 1 ev -A- 2- (p-Amino-phenylamino) -5-carbethoxyamino-

204 g 2- (2,3-dimethylphenylamino-5-nitro-pyndm 50 ^KV . * ■ ■> .J ^J

are reduced as in Example 14 with Raney nickel. '.

The reaction product is distilled in vacuo. 15 g of 2-p-nitro-phenylamino-5-carbäthoxy-amiπo-

_{B.p. 0j7} 200 to 205 ° C; M.p. 105 ^° C; Yield: 163 g. pyridine in 500 ml of dioxane are added after the addition of 3 g 51.3 g of 2- (2,3-dimethylphenylamino) -5-amino-pyri- Pd / C (10%) and 20 g of magnesium sulfate at 40 atmospheres and din as in Example 14 hydrogenated with 55 40 ^{0 C chloroformic acid.} 20 ml of ethyl ester are added to the filtered solution. M.p. 128 ^° C; Yield: 56 g. 6 η isopropanolic hydrochloric acid and causes the precipitated syrup to crystallize by rubbing. The sucked-off substance is recrystallized from methanol / isopropanol _in each _{case 6} . Mp. 248 to 250 ⁰ C; Yield: 9g.

* · 60

2- (2,3-Dimethylphenylamino) -5-morpholino- Example 21

carbonylamino-pyridine 2-amino-3-carbethoxyamino-6-phenylamino-

20 g of 2- (2,3-dimethylphenylamino) -5-carbethoxy-pyndm

. aminopyridine with excess morpholine 65 A solution of 140 g of 2-amino-3-nitro-6-phenyl-

Heated to 130 ° C for 2 hours. The reaction product aminopyridine in 500 ml of dioxane is after the addition of

is recrystallized from methyl ethyl ketone. Mp 166 ° C; 20 g Raney nickel and 60 g sodium sulfate at 40 atm

Yield: 6 g. hydrogenated. The filtered solution is immediately

7 8

Ren mixed with 100 ml of ethyl chloroformate. _Bp 195 to 215 ° C; Mp. 127 to 128 ⁰ C. From

The crystallized substance is filtered off with suction, with 103 g.

Washed water and acetone and from water to 15 g of 2- (p-toluidino) -5-aminopyridine are in

crystallized. Mp. 208 to 209 ^° C; Yield: 82 g. Mix 150 ml acetone with 10 ml propionic anhydride

5 sets and heated ^{to 50 0 C.} Then dilute sodium hydroxide solution is shaken with Example 22, whereupon the end

2-Phenylamino-3-amino-5-carbethoxyamino-pyridine product precipitates. It is converted once from methanol

crystallized. M.p. 201-202 C; Yield: 11g. 9 g of 2-phenylamino-3,5-dinitro-pyridm in 150 ml

After adding 0.5 g of Pd / C (10%), dioxane becomes at ιό B e i s ρ i e 1 28

Hydrogenated atmospheric pressure and 4O ⁰ C. The filtered solution 2- (p-toluidino) -5-carbäthoxyamino-pyridine

is then stirred with 5 ml of chloroformic acid

ethyl ester was added and the mixture was stirred for 2 hours. The 15 g of 2- (p-toluidino) -5-aminopyridine (prepared

Falling substance is recrystallized from ethanol / ether according to Example 27), dissolved in 100 ml of acetone, are in sated. Yield: 7 g; Mp 232-235 ° C. 15 Presence of 6 ml of pyridine while cooling with 8 ml

Ethyl chloroformate implemented. The Reak example 23 tion mixture becomes alkaline with dilute sodium hydroxide solution

2-p-Methylphenylamino-3-amino-5-carbethoxy- f ₊ ^mach f ' ^where f ^u [ ^ s product precipitates and once

• ·, · ethanol is recrystallized. M.p. 160 C; Yield:

~ ^Py 20 10.5 g.

50 g of 2-p-methylphenylamino-3,5-dinitro-pyridine in B e i s ρ i e 1 29

? ί? ο? ΐ? ί ° ί? ^η ™ ;? ^εΐ \ ^Unte f «^? · ^{η 5} i ^Pd / ^C 2- (4-ethoxyanilino) -5-carbethoxyamino-pyridine

(10 ° / ₀₎ was hydrogenated at normal pressure and 4O ⁰ C. To the ^v '*

filtered solution is added with stirring 18 ml of chlorine- This compound was prepared analogously to Example 28

ethyl formate. After 2 hours it is turned off and recrystallized once from isopropanol, suction and the substance from methanol / isopropanol to mp 148 to 149 ° C; Yield: 73% of theory, crystallized. Mp. 258 to 260 ⁰ C; Yield: 25 g.

Example 30

Example 24 2-Phenylamino-3-acetaminopyridine

2- (2,3-Dimethylphenylamino) -3-amino-5-carbethoxy- ³ ° ... "_,,. _., .,. ,

amino-uvridine ¹⁰ ° ^{g of} 2-phenylamino-3-nitro-pyndm are in

^v 500 ml of methanol in the presence of 10 g of Raney nickel

36 g of 2- (2,3-dimethylphenylamino) -3,5-dinitro-pyri- hydrogenated at 50 ° C and 20 to 30 atm. After evaporation

din in 400 ml of dioxane, after addition of 5 g of the solvent, the residue in vacuo Pd / C is hydrogenated at normal pressure and at 40 ⁰ C (10 7o). The 35 distilled. At 11 Torr the base distilled at 22O ⁰ C solution after filtration with stirring over and has shifted after recrystallization from isopropyl-12 ml of ethyl chloroformate. The aus- panol has a melting point of 142 ° C.

fallen substance is recrystallized from a lot of water. 18.5 g of the resulting ^ -phenylamino-ß-amino-

Mp 261-263 ° C; Yield: 6 g. pyridins are in 40 ml of dioxane at 40 ⁰ C with 9.5 ml

rv 40 acetic anhydride implemented. The solution is made with benzene

Example 25 diluted and shaken with dilute sodium hydroxide solution.

2- (o-Toluidino) -5-propionylamino-pyridine ^Na f separating off the aqueous phase is the benzene

^v jffj rs evaporated. The residue crystallizes from isopro-

20 g of 2- (o-toluidino) -5-aminopyridine (prepared panol / petroleum ether. Mp. 102 ° C.
according to Example 14) in 50 ml of acetone with 9.5 ml of 45
Propionic anhydride added. The reaction product Example 31

precipitates in crystalline form. Mp 154 ° C (from isopropanol); From 2- (2-methoxyanilino) -5-carbethoxyamino-pyridm

Loot: 11 g.

B e i s ρ i e 1 26 To 20 g (0.094 mol) 2- (2-methoxyanilino) -5-amino-

^pyn (0.094 mol) ethyl chloroformate was added dropwise.

25 g of 2- (3-trifluoromethylanilino) -5-amino-pyridin After 30 minutes of heating at 50 ⁰ C water is to-

(produced according to Example 6) are added in the presence of, an oily product being removed from the solution ml of pyridine in 100 ml of acetone with 12 g of pivalic acid is separated. That after two days of standing from the

Chloride added. After dilution with water, the product that has crystallized out in oil is filtered off with suction, dried

Chloroform added. The solvent is net and recrystallized twice from toluene / petrol

evaporated and the residue from isopropanol / petroleum siert. Mp 111-112 ° C.

ether recrystallized. Mp. 13O ⁰ C; Yield: 17 g. The starting compound is obtained by reducing

60 2- (2-methoxyanilino) -5-nitro-pyridine analogous to Example 14

B e i s ρ i e 1 27 obtained. ■

2- (p-Toluidino) -5-propionylamino-pyridine egg spat

, _ΟΛ ",. .,. , 2- (3-methoxyanilino) -5-carbethoxyamino-pyridine
180 g of 2- (p-toluidmo) -5-mtro-pyndin, suspended in 1.31 methanol, are prepared in the presence of 65. This compound is prepared analogously to Example 31. 35 g of Raney nickel hydrogenated at 60 ° C. and 50 atm. When working up, the product is obtained in crystallized form. the catalyst is then filtered off with suction and the filtrate is recrystallized from toluene. Mp. 123 until evaporated and the residue is distilled. 125 ° C.

Example 33
2- (4-methoxyanilino) -5-carbethoxyamino-pyridine

This compound is prepared analogously to Example 21 and is obtained in crystalline form on working up. she will recrystallized from methanol. Mp. 147 to 148 ° C.

Example 34
2- (4-butoxyanilino) -5-carbethoxyamino-pyridine

With stirring, to 35 g (0.136 mol) of 2- (4-Butoxyanilino) -5-amino-pyridine and 10.8 ml (0.136 mol) of pyridine in 200 ml of acetone 13 ml (0.136 mol) of ethyl chloroformate at 20 to 3O ⁰ C. added dropwise. After 40 minutes of heating at 40 to 50 ⁰ C is mixed with water, wherein an oil is separated which crystallizes after some time. The crystals are filtered off with suction, washed with water and dried. The dry crystal mass is rubbed with ether, filtered off with suction, washed a few times with ether and then recrystallized from isopropanol / petrol. Mp. 120 to 121 ° C,

The starting compound is obtained by reducing 2- (4-butoxyanilino) -5-nitro-pyridine analogously to the example 1 received.

Example 40
2- (2-Isopropylanilino) -5-carbethoxyamino-pyridine

To a solution of 29.5 g (0.13 mol) of 2- (2-isopropylanilino) -5-amino-pyridine and 10.5 ml pyridine (0.13 mol) in 150 ml of acetone at 20 to 3O ⁰ C. 12.5 ml (0.13 mol) of ethyl chloroformate were added dropwise with stirring. When the dropping is complete

ίο the temperature increased to 40 to 50 ° C for 30 minutes. Then water is added to the reaction mixture until it becomes cloudy. After a while it crystallizes Product off, it is filtered off with suction, washed with methanol / water 1: 1 and recrystallized from methanol.

Mp. 139 to 140 ° C.

The starting compound is obtained analogously to Example 27.

Example 41
2- (2,4-dimethylanilino) -5-carbethoxyamino-pyridine

This compound is obtained analogously to Example 40 from 2- (2,4-dimethylanilino) -5-aminopyridine. Fp. 152 to 153 ° C.

Example 35
2- (2,4-dichloroanilino) -5-carbethoxyamino-pyridine

- ₀ example 42

2-Amino-3-propionylamino-6-phenylamino-pyridine

This compound is prepared analogously to Example 31 and recrystallized from isopropanol / gasoline. M.p. 141 up to 142 ° C.

Example 36
2- (2,5-dichloroanilino) -5-carbethoxyamino-pyridine

This compound is prepared analogously to Example 31 and recrystallized from isopropanol / gasoline. Mp. 132 to 133 ^° C.

Example 37.
2- (3,4-dichloroanilino) -5-carbethoxyamino-pyridine

This compound is prepared analogously to Example 31 and recrystallized from isopropanol. Mp. 146 to 147 ⁰ C.

Example 38

2- (2,4-dimethoxyanilino) -5-carbethoxyaminopyridine

This compound is produced analogously to Example 31. When working up, the reaction product initially also precipitates as an oil, but solidifies after a short time. The crystals are filtered off with suction, washed with water, dried and each time from toluene / petrol and isopropanol / petrol recrystallized. Mp. 117 to 118 ° C,

Example 39
2- (2,3-dichloroanilino) -5-carbethoxyamino-pyridine

. This compound is prepared analogously to Example 31 and recrystallized from isopropanol / gasoline. Mp. 129 to 13O ⁰ C.

The procedure is analogous to Example 21, but instead of ethyl chloroformate 70 g of propionyl chloride are used. The reaction product is made from ethanol recrystallized. Mp 213-218 ° C; Yield: 95 g.

B e i s ρ i e 1 43

2-Amino-3-carbethoxyamino-6- (2,3-dichlorophenyl) -amino-pyridine

A solution of 27 g of 2-amino-3-nitro-6- (2,3-dichlorophenyl) -amino-pyridine in 400 g of dioxane is hydrogenated as in Example 21. The filtered solution is reacted with 18 ml of ethyl chloroformate with stirring. The reaction product which has crystallized out is filtered off with suction after 2 hours and recrystallized from a little isopropanol. . Mp 194-195 ⁰ C; Yield: 14 g.

Test report

The compounds according to the invention were on the protein edema of the rat paw by the method of Domen j oz and coworkers (cf. Arch. Exp. Pharm. Path., 230, p. 325 [1957]), on anti-inflammatory Checked effect. The anti-inflammatory effect is compared to the percentage of edema inhibition untreated control group indicated. It was applied orally in all experiments. The dose was always 300 mg / kg rat.

The toxicity test was performed orally on the mouse by determining the acute toxicity (LD 50 mg / kg) Miller and Tainter (see Proc. Soc. Exper. Biol. And Med., 57, 1944). The observation time was 24 hours.

The well-known anti-inflammatory phenylbutazone was chosen as a comparison substance. The results are contained in the following table:

Protein edema LD 50 mg / kg substance inhibition
in ° / ₀ at orally example 300 mg / kg No. orally mouse rat 3300 1 77 about 3000 2 84 558 3 86 about 1000 5 26th 11540 7th 51 4600 9 49 2500 11th 54 2000 to 4000 12th 58 (estimated) 200 to 400 intraperitoneally (Rat) about 1000 14th 38 around 2000 17th 41 about 3000 18th 35 about 1000 20th 76 133 ± 24 (rat) 21 86 165 (rat) 22nd 81 300 23 70 about 1000 24 46 around 1500 25th 55 > 4000 26th 53 > 4000 p. o. rat 27 53 around 1500 30th 42 600 42 44 > 4000 43 38 Phenyl 530 *) butazon 36

*) Rat LD 50 200 p. O.

Taking into account the tolerability, the anti-inflammatory effect of all investigated compounds is better than that of the reference substance.

Claims (2)

Patent claims: 1. Phenylamino-pyridines of the general formula I. , R ^{2 l} - CO - NH - + - I / ^ in which R ^{1 is} an alkyl radical having 1 to 5 carbon atoms, an alkpxyresi optionally substituted by a morpholino group; having 1 to 5 carbon atoms or a morpholino group, R ^{2 is} a hydrogen atom or an amino group, R ³ and R ^{4 are} identical or different and each is a hydrogen or halogen atom, an alkyl or alkoxy group with 1 to 6 carbon atoms, a trifluoromethyl or amino group and R ^{6 represents} either a hydrogen atom or the R ¹ -CO group, and their acid addition salts. 2. Process for the preparation of the compounds according to claim 1, characterized in that one in a manner known per se in a compound of the general formula II atoms, an alkoxy radical optionally substituted by a morpholino group with 1 to 5 carbon atoms or a morpholino group, R ² a hydrogen atom or an amino group, R ³ and R ^{4 are} identical or different and each have a hydrogen or halogen atom, an alkyl or alkoxy group with 1 to 6 carbon atoms, a trifluoromethyl or amino group and R ^{5 is} either a hydrogen atom or the R ¹ - CO - group, their acid addition salts and a process for their preparation, which is characterized in that in a manner known per se in a compound of general formula II