DE2337896A1 - 4-PHENYLAMINOPYRIDE DERIVATIVES - Google Patents

Description

July 18, 1973 AvK / Ax

MANUFACTURE DE PRODUITS PHARMACEUTIQUES A. CHRISTIAENS S.A., Rue de l'Etuve 60, B-IOOO Brussels (Belgium).

4-phenylaminopyridine derivatives

The invention relates to new 4-phenylaminopyridine derivatives, the production of these derivatives and medicaments containing them with valuable pharmacological properties.

The new 4-phenylaminopyridine derivatives according to the invention have the general formula

NH-

^R 6

SO ₀ NHCOR ₁

(D

in which R- is an alkyl radical with 1 to 4 carbon atoms and R ₀ , R 1, R ^, Rf- and R ^ are hydrogen atoms or methyl radicals, nitro groups, trifluoromethyl radicals or chlorine groups, with the proviso that at least one of the radicals R ₂ , R ,, R ₂ ,, R- and Rg is not a hydrogen atom and the number of substituents.

which are not hydrogen and for them

₀ , R,

and R

are not higher than 2 and with the proviso that R, is not a trifluoromethyl radical when R is a methyl radical and

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R ₀ , R ,,, R ₁ - and R _{r are} hydrogen atoms.

d. 4 O O

Preference is given to compounds of the formula (I) in which R 1 is an alkyl radical with 1 to 4 carbon atoms, Rp and R ^ are hydrogen or a methyl radical, trifluoromethyl radical or a chlorine group, R-2 and R _{5 are} hydrogen atoms or a nitro group, Are chlorine group or a trifluoromethyl radical and R ^ is hydrogen or a nitro group or chlorine group, with the proviso that at least one of the radicals Rp, R ^, R ₂ , R, - and Rg is not a hydrogen atom and the number of substituents which are not Are hydrogen and for Rp, R ,, R ^, Rc- and R- are not higher than 2 and with the proviso that R- is not a trifluoromethyl radical when R- is a methyl radical and when R ₂ , R ^ ,, Rp. And Rg are hydrogen atoms.

Examples of the new 4-phenylaminopyridine derivatives according to the invention are:

3-acetylsulfonamido-4- (3'-chloro) phenylaminopyridine 3-acetylsulfonamido-4- (3'-chloro-2'-methyl) phenylaminopyridine 3-acetylsulfonamido-4- (2'-trifluoromethyl) phenylaminopyridine 3-acetylsulfonamido-4 - (^ '- nitro) phenylaminopyridine 3-acetylsulfonamido-4- (4'-chloro) phenylaminopyridine 3-propionylsulfonamido-4- (3'-chloro) phenylaminopyridine 3-acetylsulfonamido-4- (4'-nitro) phenylaminopyridine 3-propionylsulfonamido-4- (3'-trifluoromethyl) phenylaminopyridine

3-butyroylsulfonamido-4- (3 "- trifluoromethyl) phenylaminopyridine

3-acetylsulfonamido-4- (3 ', 5'-dichloro) phenylaminopyridine 3-propionylsulfonamido-4- (3', 5'-diohlor) phenylaminopyridine 3-acetylsulfonamido-4- (3 ', 4'-dichloro) phenylaminopyridine 3- Propionylsulfonamido-4- (3 ¹ , 4'-dichloro) phenylaminopyridine 3-acetylsulfonamido-4- (2 ', 3'-dichloro) phenylaminopyridine 3-propionylsulfonamido-4- (2', 3'-dichloro) phenylaminopyridine 3-aetylsulfonamido 4- (2 ', 4'-dichloro) phenylaminopyridine 3-propionylsulfonamido-4- (2', 4'-dichloro) phenylaminopyridine

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J-acetylsulfonamido - ^ - (2 ', 5'-dichloro) phenylaminopyridine 3-propionylsulfonamido-4- (2', 5'-dichloro) phenylaminopyridine i 5-acetylsulfonamido-4- (2 ', 6'-dichloro) phenylamine pyridine. 5-propionylsulfonamido-4- (2 ^l , 6'-dichloro) phenylamino pyridine

invention

The / also includes the preparation of the compounds of the general Formula (I). These connections can be made using two methods:

First procedure

Acylation of ^ -Sulfonamido- '^ - phenylaminopyridine (II) with Carboxylic acid chlorides or anhydrides with 2 to 5 carbon atoms in the presence of pyridine:

SO ₂ NH ₂

+ Carboxylic acid chloride or anhydride

, - SO ₂ NHCOR ₁

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Second method

Condensation of 4 ~ chloropyridino-5-acylsulfonamides (III) with substituted aromatic amines (IV) / in the presence of toluene and copper powder or in the absence of a solvent by heating to a temperature between 80 and 150 ⁰ C:

B ₂ ^R 6 H ₂ N R ^ ^. ^R 5 + - ^R 3 I. ^R 3 ^R 4 (IV)

The invention is also directed to pharmaceutical preparations with a diuretic and / or anti-inflammatory effect which contain as active ingredient at least one 4-phenylaminopyridine derivative of the general formula (I) in which R- is an alkyl radical with 1 to 4 carbon atoms and Rp, R ,, R ^, R ₁ , and Rg are hydrogen atoms or methyl radicals, nitro groups, trifluoromethyl radicals or chlorine groups with the proviso that we

at least one of the leftovers

R ₁ - and R ^ - no water

material atom and the number of substituents that are not a water

are fabric and for the

R ,, R

R ₅ and

stand, do not

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- 5 is higher than 2.

It has been found that the compounds of formula (I) are excellent have diuretic and / or anti-inflammatory properties. Some of the compounds of formula (I) have Far better diuretic properties than the known diuretics, e.g. hydrochlorothiazide (ESIDREX), chlorthalidone (HYGROTON) and acetazolamide (DIAMOX).

in '

Diuretic properties were determined for the following compounds: 3-Aeetylsulfonamido-4- (3'-trifluoromethyl) phenylaminopyridln (Formula I, R-, = CHy R, = CFy R ₃ = R ₂ J = R ₅ = R ₆ = H) , 3-propionylsulfonamido-4- (3'-trifluoromethyl) phenylaminopyridine (formula I, R ₁ = C ₂ H ₅ ; R, = CFy R ₃ = R ₂ J = R ₅ = R ₆ = H), 3-propionylsulfonamido- 4- (3'-chloro) phenylaminopyridine (formula I, R, = C ₃ H ₁ -; R ^ = Cl; R ₂ = R ₂ I = R ₅ = R ₆ = H), 3-acetylsulfonamido-4- (3'-chloro) phenylaminopyridine (Formula I, R ₁ = CHy R ₅ = Cl; R ₃ = R ₂ J = R ₅ = R ₆ = H), 3-butyroylsulfonamido-4- (3 '-trifluoromethyl) phenylaminopyridine (Formula I, R-, = C 'H ₇ ; R-, = CF- ,; R ₃ = R ₂ ^ = R ₅ = R ₆ = H), 3-acetylsulfonamido-4- (4'-chloro) phenylaminopyridine (Formula I, R ₁ = CHy R ₂ J = Cl; R ₂ = Ry = R ₅ = R ₆ = H), 3-acetylsulfonamido-4- (3'-nitro) phenylaminopyridine (Formula I, R ₁ = CH ₅ ; R ^ = NO ₂ ; R ₂ = R ₂ J = R ₅ = Rg = H), 3-acetylsulfonamido-4- (3'-chloro-2'-methyl) phenylaminopyridine (formula I, R ₁ = CHy R, = Cl; R ₂ = CH, and Rr = R ₅ = R ₆ = H), 3-acetylsulfonamido-4- (4 ^l -chlor) phenylaminopyridine (Formula I, R ₁ = CHy R ₂ J = Cl; R ₂ = R = R = R ₆ = H), and 3-acetylsulfonamido-4 (3'-chloro-4 · -chlor) -phenylaninopyridine (Formula I, R-, = CH ₁ ,; R ^ = Cl; R ₂ J = Cl

and R ₀ = R ₁ - ^ RzT = H). These compounds can therefore be found in the Arz-2 5 ο

neimittelpreparations can be used according to the invention.

Some compounds of formula (I) have far better anti-inflammatory properties Properties as known anti-inflammatory compounds, e.g. acetylsalicylic acid, phenylbutazone, Flufenamic acid and niflumic acid.

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The compounds 5-acetylsulfonamido-4- (3 ¹ , 5'-dichloro) phenylaminopyridine (formula I, R ₁ = CH ₃ ; R ₃ = Cl; R ₅ = Cl and R ₃ = R ₄ = R ₆ =) have anti-inflammatory properties H); 3-propionylsulfonamido-4- (3 ', 5'-dichloro) phenylaminopyridine (Formula 1, R ₁ = C ₂ H ₅ ; _ R ₂ = Cl; R ₅ = Cl and R ₃ = R ₄ = R ₆ = H) , 3-acetylsulfonamido-4- (2 ', 3'-dichloro) phenylaminopyridine (Formula I, R-, = CH ₃ ; R ₂ = Cl; R ₃ = Cl and R ₄ = R ₅ = Rg = H); J5-propionylsulfonamido-4- (2 ', 3'-dichloro) phenylaminopyridine (Formula I, R ₁ = CJl ₁ -; R ₂ = Cl; R ₅ = Cl and R ₂₁ = R ₅ = Rg = H); ^ -Acetylsulfonamido - ^ - (2 *, -4 ^! -Dichlor) phenylaminopyridine (Formula I, R ₁ = CH ₃ ; R ₂ = Cl; R ₄ = Cl and R ₃ = R ₅ = R ₆ = H); 3-propionylsulfonamido-4- (2 ', 4'-dichloro) phenylaminopyridine (Formula I, R ₁ = CgH ₁ -; R ₂ = Cl; R ₄ = Cl and R ₃ = R = Rg = H) and 3-propionylsulfonamido -4- (2 ^f , 6'-dichloro) phenylaminopyridine (Formula I, R-, = CpHj-; R ₂ = Cl; Rg = Cl and R ₃ = R ₄ = R ^ = H). These compounds can therefore be used in the pharmaceutical preparations according to the invention.

Finally, it has been found that some compounds of formula (I) have both diuretic and anti-inflammatory properties. Of these compounds, the following may be mentioned: 3-acetylsulfonamido-4- (2 ', 5'-dichloro) phenylaminopyridine (formula I, R ₁ = CH ₃ ; R ₂ = Cl; R ₅ = Cl and R ₃ = R ₄ = Rg = H), 3-propionylsulfonamido-4- (2 ', 5'-dichloro) phenylaminopyridine (Formula I, R ₁ = CH ₃ ; R ₂ = Cl; R ₁ - = Cl and R = R ₄ = Rg = H ). These compounds can therefore also be used in the pharmaceutical preparations according to the invention.

The invention is further illustrated by the following examples:

example 1 ^v

Manufacture of JS-Acetylsulfonamido - ^ - (3'-trifluoromethyl) -

phenylamxnopyridine

First procedure ; A mixture of 9 g of ^ -Sulfonamido- ^ l- (3'-trifluoromethyl) phenylaminopyridine, 46 ml of anhydrous pyridine and 45 g of acetic anhydride is in a reaction

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2337836

barrel stirred in the absence of moisture for 24 hours at room temperature. The mixture is then poured onto ice. The precipitate formed is filtered off and treated with a concentrated sodium hydroxide solution. After filtering off the insoluble material, the solution is neutralized with hydrochloric acid. The solution is then extracted with ethyl acetate. The residue obtained by evaporation is extracted with an aqueous 5 # sodium bicarbonate solution. After filtration and clarification with activated charcoal, the filtrate is acidified. After the precipitate obtained has been recrystallized several times from a mixture of benzene and cyclohexane, a product with a melting point of 178 ^° C. is obtained in a yield of 47.5 % .

It is possible to obtain crystals of the product with 1 molecule of water of crystallization is removed by drying under reduced pressure at 110 ⁰ C.

Second method : A solution of 0.1 mol of m-trifluoromethylaniline in toluene is slowly added to a boiling suspension of 0.1 mol of 4-chloropyridino-5-acetylsulfonamide in toluene in the presence of a trace of copper powder. After the addition is complete, the reaction mixture is heated for 15 minutes. After cooling, 5 parts by volume of petroleum ether (boiling point 50 to 75 ° C.) are added. The precipitate obtained is filtered off and treated with an aqueous 5% sodium bicarbonate solution. The suspension is filtered and the filtrate, which has been clarified with activated charcoal, is acidified, the desired product being precipitated.

Third method : 0.1 mol of 4-chloropyridino-5-acetylsulphonamide and 0.1 mol of m-trifluoromethylaniline are heated in an open stirred tank in the presence of a trace of copper powder. After a temperature of 80 to 100 ^° C. has been reached, spontaneous heating takes place, the temperature rising ^{rapidly to 120 ° C.} After cooling down immediately, the

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ne mass dissolved in a mixture of acetone and water (6O: 4o). The resulting solution is filtered and evaporated to dryness. The residue is washed with a 5 # solution of sodium bicarbonate treated. The solution obtained is filtered and the filtrate is acidified, the desired product precipitating will.

All of the procedures described in this example are also general to the preparation of those in the following examples described compounds applicable.

Example 2

Preparation of 3-propionlysulfonamido-4- (3'-trifluoromethyl) -phenylaminopyridine

9 g of 3-sulfonamido-4- (3'-trifluoromethyl) phenylaminopyridine, 46 ml of anhydrous pyridine and 45 g of propionic anhydride are mixed at room temperature for 24 hours with exclusion of moisture. The first process described in Example 1 gives white crystals of the desired product which, after a few recrystallizations from a mixture of cyclohexane and benzene, melts at 163 ° to 165 ° C. (yield 6%>).

The same product can also be used according to that described in Example 1 second method or third method.

Example 3 Production of 3-butyroylsulfonamido-4- (3'-trifluoromethyl) -

phenylaminopyridine

A mixture of 1.5 g of 3-sulfonamido-4- (3'-trifluoromethyl) -phenylaminopyridine, 7 * 5 g of anhydrous pyridine and 11.55 g of butyric anhydride is stirred at room temperature for 18 hours with exclusion of moisture. In the manner described in Example 1 (first process), white crystals with a melting point of 158 to 160 ° C are obtained in a yield of 42 %

obtain.

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Example 4

Preparation of 3-butyroylsulfcnamido-4- (3'-trifluoromethyl) -phenylaroinopyridine

A rack of 1.5 g of 3-sulfonamido-4- (3'-trifluoromethyl) phenylaminopyridine, 0.5 S butyroyl chloride and 10 ml of anhydrous pyridine is stirred for 20 hours at room temperature with exclusion of moisture. The mixture obtained is poured onto ice and the precipitate is filtered off. After a few recrystallizations from benzene, the product melts
158 to 160 ° C. Yield 55 %.

Example 5

Preparation of 3-acetylsulfonamido-4- (3'-chloro) phenylaminopyrldine

A mixture of 10 g of 3-sulfonamido-4- (3'-chloro) phenylaminopyrldine, 50 g of anhydrous pyridine and 50 g of acetic anhydride is taken for 5 hours at room temperature with exclusion
stirred by moisture. The resulting mixture is on
Poured ice and filtered off the precipitate formed and treated successively with sodium hydroxide and sodium bicarbonate as described in Example 1. After a few recrystallizations from a mixture of benzene and methanol, white crystals with a melting point of 218 ° C. become in one yield
received by 84 % .

Be is ρ i e 1 6

Preparation of 3-propionylsulfonamido-4- (3'-chloro) phenylaminopyridine

The compound is prepared in the manner described in Example 5, but with propionic anhydride instead
of acetic anhydride is used. White crystals with a melting point of 172 to 173 ° C are produced in a yield of
80% received.

Example 7

Preparation of ^ -Acetylsulfonamido ^ - (3'-chloro-g'-methyl) - pheriylaminopyridine

3Ö9886 / 1178

- ίο -

This compound is prepared in the manner described in Example 1 (first method) using 3-sulfonamido-4- (3 * - chloro-2'-mechyl) phenylaminopyridine instead of 3-sulfonamido-4- (3'-trifluoromethyl) -phenylaminopyridine manufactured. White crystals with a melting point of 212 to 214 ° C. are obtained.

Example 8 Production of 3-acetylsulfonamido-4- (2 ^t -trifluoromethyl) -

phenylaminopyridine

This compound is prepared in the manner described in Example 1 and in the form of white crystals of melting point 192 to 193 ° C.

Example 9

Preparation of 3-acetylsulfonamido-4- (3 ^f -nitro) phenylaminopyridine

This compound is made in the manner described in Example 1. The product (melting point 212 ° C.) crystallizes with 1 molecule of water of crystallization, which can be removed by drying under reduced pressure at 110 ° C.

Example 10

Manufacture of .l-Acetylsulfonamido - ^ - CV-chlor ^ henylamino-

pyridine

This compound is obtained in the manner described in Example 1 in the form of white crystals with a melting point of 193-19 ° C manufactured.

Example 11

Production of 3-acetylsulfonamido-4- (4'-nitro) phenylamino-

pyridine

This compound is molded in the manner described in Example 1

represents.

manufactured in the form of yellow crystals of melting point 230 ⁰ C

Examples 12 to 23

The compounds listed in Table I below are like

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- li -

follows produced.

1 g of 3-sulfonamido-4-dichlorophenylaminopyrldine is kept in contact with 5 "acetic or propionic anhydride in 5 ml of pyridine for 1 to 3 hours. The reaction mixture is poured into 100 ml of a 10% sodium hydroxide solution. The reaction mixture is stirred for a few minutes and then filtered, whereupon the p n value is adjusted to 5 to 6. After crystallization, the crystals are isolated, washed with water and washed in 100 ml of 5% sodium bicarbonate solution in a mixture of water and ethanol (3: 1) The desired compound is recrystallized when the Pjj value is set to 5 to 6. Yield 70 to 90 %.

Table I. τ ^R l j. R ₃ , R ₄ , -R ₅ , R ₆ Melting point CH ₃ / compounds of the formula I ¹ 5'-Cl ⁰ C example C ₂ H ₅ R ₂ or R ₃ 5'-Cl 224-225 12th 3'-Cl 4'-Cl 190 - 192 ' 13th C ₂ H 3'-Cl 4'-Cl 212-214 14th 3'-Cl 3'-Cl I88-190 15th C ₂ H ₅ 3'-Cl 3'-Cl I98-199 16 CH ₃ 2'-Cl 4'-Cl. 197 - I98 17th C ₂ H ₅ 2'-Cl 4'-Cl I85 18th CH ₃ 2'-Cl 5'-Cl 149 19th C ₂ H ₅ 2'-Cl 5'-Cl 198 20th CH ₃ 2'-Cl 6'-Cl 186 - I87 21 Often- 2'-Cl 6'-Cl 23Ο 22nd 2 '-Cl 222-223 23 2'-Cl

The unspecified radicals Rp, R ^, R ^ ,, Rp. And R / - are hydrogen atoms.

example

24

Pharmacological tests to determine the luretic effect
Groups of 5 rats each weighing 250 to 300 g

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were compiled at random. Each animal was subjected to the same treatment. The animals were fasted 18 hours before the experiment, but they were given drinking water ad libitum. On the day of the experiment, the test compound was fed into the gastric tube at a dose of 100 mg / kg as a solution or suspension in water containing 0.45 % Methocel ( an inert slimy substance). The control animals received only distilled water as a placebo. At the same time, all animals received 25 mg / kg of physiological saline by subcutaneous injection. The rats were placed in metabolic cages and each cage contained 5 animals, which were processed in the same manner The urine was collected over a period of 4 hours. The increase in urine volume in the treated animals compared to the urine volume in the comparison animals shows the diuretic effect. The diuresis is expressed in ml / kg body weight. The results of the experiment are mentioned below in Table II.

Table II

Urine volume, ml / kg / compound, 4 hours

Hydrochlorothiazide (ESIDREX) 33.0

Chlorothalidone (HYGROTON) 26.6

Acetazolamide (DIAMOX) 27.5

Placebo (comparison animals) 8.7

Compound of Example 2 71.7

Example 6 63.4

Example 5 60.7

Example 1 52.5

Example 3 48.0

Example 10 40.6

Example 9 25.4

Example 7 23.2

Example 11 21.9

Example 14 24.8

Example 20 40.9

Example 21 18.7

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OWGlNAL \

Example 25

Pharmacological tests to determine the anti-inflammatory properties

The test compounds are administered orally as freshly prepared solutions or suspensions one hour before the injection of carrageenin, a known inflammatory agent, into a paw of the rat. The inflammatory agent (carrageenin) is then injected in solution or suspension into the plantar tissue of the right hind paw of each rat. The left paw remains untreated and is used for comparison. Each animal receives, for example, 0.05 ml of an aqueous solution containing 1 wt -.% Carrageenin and containing 0.9% sodium chloride.

Four hours after injection of the inflammatory agent, the size of the swelling is measured by plethysmography and expressed as a percentage of the volume of the reference paw. The anti-inflammatory effect as a percentage inhibition is made by comparing the rats treated with the anti-inflammatory compound with a control group of Rats identified. The results of tests carried out with a number of compounds of the formula (I) are listed in Table III below.

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Table III

Connection of example

Percentage of carrageenin-induced acute edema inhibition

12 13 15 16

17 18

19 20 21

Phenylbutazon acetylsalicylic acid Flufenamsätre (flufenamic acid) Nii'luminsäure (niflumic acid) 53
22nd

54
36
41
20th
34
17th
15th
13th
41
0

34 32

example

26th

Coated tablets

Core: compound of formula (i) (e.g. 3-propionylsulfonamido-4- (5'-trifluorinethyl- or -3 'chloro) -phenylaminopyridine) Colloidal Silica Lactose Polyvinylidone Glycerin Corn Starch Talc

Magnesium stearate blanket: shellac Gum arabic "Ne ν; - coc a" dye Talc Colloidal Silica Sucrose

303 8 86/11 7 P per coated tablet

50.0 mg 5.0 mg

42.5 mg 3.5 mg 0.5 mg 8.0 mg

10.0 mg 2.0 mg 2.0 mg 5.4 mg 0.1 mg

13.0 mg

Q, 5 mg 50.0 mg

These dragees can be used as diuretics in a dose of 50 to 100 mg / day can be administered.

Example 27 Tablets

Compound of Formula (I) 200.0 mg

Colloidal silica 17 * 0 mg

Stearic acid 4.0 mg

Gelatin 4.0 mg

Glycerin 1.6 mg

Corn starch 52.0 mg

Magnesium stearate 1.4 mg

These tablets can be administered as diuretics and / or anti-inflammatory agents in a daily dose of 100 to 300 mg will.

Example 28 Capsules

Compound of Formula (I) 100.0 mg

Lactose 120.0 mg

Rice starch 30.0 mg

Corn starch 30.0 mg

Magnesium stearate 5 * 0 mg

Gelatine) _wrapping 78.0mg

Tartrazine ί 0.2 mg

These capsules can be administered as diuretics and / or anti-inflammatory agents in a daily dose of 200 mg

ORiGINAL INSPECTED 309886/1178

Example 29 Suppositories

Compound of formula (i) 3> 00 mg

Witepsol H, p ⁺ 600 mg

⁺ Mixture of triglycerides and partial glycerides of saturated fatty acids (^ ρ-Ο, ο) from plants; Manufacturer Dynamit Nobel.

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Claims (1)

Patent claims 4-Phenylaminopyridine derivatives of the general formula -SO ₂ NHCOR ₁ in the
R ₂ , R is an alkyl radical with 1 to 4 carbon atoms and, Rt- and R ^ for hydrogen or a methyl radical, a nitro group, a trifluoromethyl radical or a chlorine group are with the proviso that at least one the remainder of R R ₁ and is no hydrogen and the number of substituents which are not hydrogen and for which Rp, R ,, R ₂ ,, Rp. and Rg stand is not higher than 2 and with the proviso that R ^, is not a trifluoromethyl _{radical when R 1 is} a methyl radical and R ₂ , R ₂ ^, R ₁ - and Rg are hydrogen. 2. 4-phenylaminopyridine derivatives according to claim 1 with the formula mentioned there, in which Ri is an alkyl radical with 1 to 4 carbon atoms, R ₂ and Rg are hydrogen or a methyl radical, trifluoromethyl radical or a chlorine group, and R ₁ stand for hydrogen or a nitro group, chlorine group or a trifluoromethyl radical and R ^ is hydrogen or a nitro group or chlorine group with the proviso that at least one of the radicals R ₂ , R- ,, R ₂ ^, Rt- and Rg is not hydrogen and the The number of substituents R ₂ , R 1, R _2. , Rk and Rg which are not hydrogen is not higher than 2 and with the proviso that R _{1 is not a trifluoromethyl radical when R 1 is} a methyl radical and R ₂ , R ₂ ,, Rt- and Rg are hydrogen. 309886/1178 5. 4-phenylaminopyridine derivatives according to claim 2, characterized in that R .. is an alkyl radical having 1 or 2 carbon atoms, R- is a chlorine group and Rp, Eu, Rf- and Rg have the meanings given in claim 2. 4. 4-phenylaminopyridine derivatives according to claim 2, characterized in that R «is an alkyl radical having 1 or 2 carbon atoms and R- * or R _{2+ are} a trifluoromethyl radical or a chlorine group and Rg, R, - and R / - are have the meanings mentioned in claim. 5 x 3-propionylsulfonamido-4- (3 ^f -trifluoromethyl) phenylaminopyridine 6. 3-propionylsulfonamido-4- (3'-chloro) phenylaminopyridine 7 · Medicinal preparations with diaretic and / or anti-inflammatory effect, containing at least one compound according to claim 1 to 5 as an active ingredient and pharmaceutically acceptable carriers. 8. Process for the preparation of 4-phenylaminopyridine derivatives according to claims 1 to 6, characterized in that 3-sulfonamido-4-pheny! aminopyridines of the general formula -SO ₂ NH ₂ in the R ₂ , R and those mentioned in claim 1 Have meanings with a carboxylic acid chloride or anhydride having 2 to 5 carbon atoms in the presence of pyridine implements. 309886/1 178 9. Process for the preparation of 4-phenylaminopyridine derivatives according to Claim 1 to 6, characterized in that 4-chloropyridino-5-acy! Sulfonamides of the formula in which R «is an alkyl radical having 1 to 4 carbon atoms, with a substituted aromatic amine of the formula in the R ₀ , _lo , R ,, Ri ₁ , Rf- and R / r those mentioned in claim 1 d. J H P D Have meanings condensed in the presence of copper powder. 309886/1178