DE2461059A1 - NEW 5,7-DISUBSTITUTED XANTHONE-2-CARBONIC ACID DERIVATIVES AND METHOD FOR THEIR PRODUCTION - Google Patents

Description

PATENT APPLICATION M-TE

DipL-lng. P. WIRTH ■ Dr. V. SCHMIED-KOWARZlK Dlpl.-lng. G. DANNENBERG Dr. P. WEINHOLD Dr. D. GUDEL

281134 6 FRANKFURT / M.

TELEPHONE (Οβίη _287oi4 GR ESCHENHEIMER STR. 39

PA-529 A / Add.

,. ! öalagexempiar

SYNTEX (U.S.A.) Inc. \ I rijiMw

Palo Alto (Calif.) / USA.

New 5,7-disubstituted xanthone-2-carboxylic acid derivatives and methods of making them

(Addition to P 22 34 254.7)

The main patent (application P 22 34 254.7) concerns certain 5,7-disubstituted xanthone-2-carboxylic acid derivatives and processes for their preparation. Those compounds in which one of the substituents fall within the scope of the main patent represents a lower alkyl or lower alkoxy radical each having 1 to 5 carbon atoms, was used in further experiments a new class of compounds that matches the compounds of the main patent is closely related, the compounds of the new class being at least equally good, if not better Have properties than the compounds of the main patent. The new class of compounds is 5,7-disubstituted Xanthone-2-carboxylic acid derivatives, in which one

the sub

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Input blind stamping with head (Japan) 74

An alkyl or alkoxy substituent is 6 to 12 each Is carbon atoms.

The invention thus relates to compounds of the following. formula

OOH

and their pharmaceutically acceptable, non-toxic esters, Amides and salts, ■

wherein a radical R is an alkyl or alkoxy radical with each 6 to 12 carbon atoms and the other R is the remainder

represent, where η is the number 1 or 2 and. R denotes a lower alkyl radical.

5-Alkyl- (Cg-CLp) -T- (R ) ~ xanthone-2-carboxylic acid ~ compounds, "

- (C ^ -C. ₂ ) _7- (R) -xanthone-2-carboxylic acid compounds, (Cg-C ₁₂ ) -5- (R) -xanthone-2-carboxylic acid compounds and 7-alkoxy- (Cg -C -) - 5- (R) -xanthone-2-carboxylic acid compounds, in which R ₂ is a lower alkylsulphinyl or lower alkylsulphonyl radical which can be represented by the following formulas (1) to (4).

5098 2 9/098 8

(i)

ΟΟΗ

COOH

OR

(2)

COOH

(3)

(4)

COCK

as well as the pharmaceutically acceptable, non-toxic esters,

Amides and salts, where R has the meaning given above and E ⁵ , R ⁴ ", R ⁵ and R ^{6 represent} alkyl radicals having 6 to 12 carbon atoms.

The invention also relates to methods of making certain of the novel compounds disclosed herein and of

certain disclosed in earlier application no

Links '

The invention also relates to the relief of symptoms, which occur in allergies caused by antigen-antibody (allergic) reactions. Included it is about inhibiting the effects of allergic Response by administering effective amounts of flirlc-

509829/098 8

material. It is believed that provided by the. Active ingredients the release and / or effect of toxic products, e.g. histamine, 5 ~ hydroxy-tryptamine or the SRS-A substances and others that occur as a result of a combination of a specific antibody and an antigen (allergic reaction) are formed, is inhibited. Through these properties are the compounds of the invention for the treatment of various allergic conditions useful.

The compounds according to the invention also represent relaxants smooth muscle, e.g. bronchodilators, and can therefore be used to treat related conditions v / ground, for example for the treatment of bronchial constriction. They are also vasodilators and can be used against corresponding • conditions. e.g. in kidney and heart diseases.

It is thus possible to inhibit the effects of the allergic reaction by adding an effective amount of a Compound of the following formula '

COOK

or a pharmaceutically acceptable, non-toxic ester, an amiri or salt thereof, or a pharmaceutically acceptable, non-toxic formulation containing the acid, an ester Contains amide or salt thereof as an essential component, administered,

where in the above formula R is an alkyl or alkoxy radical 6 to 12 carbon atoms each and the other Reet R

509829/0 988

a remainder:

-SO)
R '

represent, where η is the number 1 or 2 and R is a lower alkyl radical. ■. .

The invention also relates to pharmaceutical preparations To inhibit the effects of the allergic reaction, use an effective amount of a compound of the Formula:

COOH ^;

(B)

or a pharmaceutically acceptable non-toxic ester, Amide or salt thereof in admixture with a pharmaceutical permissible non-toxic carriers, where in the above formula R is an alkyl or alkoxy radical each with 6 to 12 carbon atoms and the other radical R is a radical:

represent, where η the number 1 or 2 and R a lower one Means alkyl radical.

The effective amount of a compound according to the invention or Preparation is based on any, per se known, usual

509829/0 9 88.

Administered as a single or in combination with another compound of the invention or others pharmaceutical substances such as antibiotics, and hormones. like The new compounds or preparations can thus be used orally, topically, parenterally or by inhalation in the form of solid, liquid or gaseous dosage units are administered, e.g. as tablets, suspensions and aerosols. Administration takes place in the form of individual dose units in continuous therapy or as required. Preferably administration is when symptom relief is specifically needed or is imminent. the However, compounds can also be administered continuously or for prophylactic treatment.

The effective dose can vary over a wide range depending on the severity of the condition being treated, the age of the patient, and the like, and these factors can be routinely taken into account by those skilled in the art. Generally, an effective bli ^ ^e is about o, oo5 to about 1oo mg / kg body weight per day and preferably from about o, o1 to about loo mg / kg body weight per day. In other words, the effective amount will generally be from about 0.5 to about 7,000 mg / day / patient.

Suitable pharmaceutical carriers for the manufacture of the pharmaceutical Preparations can be solids, liquids or gases. The preparations can take the form of Tablets, pills, capsules, powders, formulations for delayed release, solutions, suspensions, elixirs, Have aerosols and the like. The carriers can be selected from various oils selected from petroleum, animal, vegetable or synthetic oils, for example peanut oil, soybean oil, lineral oil, sesame oil and the like. Water, Saline, aqueous dextrose and glycole are available

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,, J

preferred liquid carriers, especially for manufacture injectable solutions. Suitable pharmaceutical Extenders are starch, cellulose, talc, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, Silica gel, magnesium stetrate, sodium stearate, glyceryl mono tearate, Sodium chloride, dried skimmed milk, glycerin, propylene glycol, water, ethanol and the like. Suitable pharmaceutical Carriers and their formulation are described in "Remingtons Pharmaceutical Sciences" by E.V /. Martin described. the corresponding formulations contained in every .Pail an effective amount of the active ingredient together with a suitable amount of carrier to make the dosage form suitable Prepare appropriate administration to the patient leaves. .

The compounds according to the invention are effective inhibitors the effects of the allergic reaction, with effectiveness in appropriate tests on passive cutaneous anaphylaxis can be measured, see e.g. J. Goose et al., Immunology, J6, 749 (T969)

Some of the compounds according to the invention can be prepared according to the following: Reaction scheme:

Reaction scheme A

coor

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OOR

COOH

COOH

In the above formulas, "halo" denotes bromine, chlorine, fluorine

• 7

or iodine and preferably bromine, R a lower alkyl radical, preferably the methyl radical, R an alkyl or alkoxy radical having 6 to 12 carbon atoms, while Ir \ R ¹ ° and H ^{11 are} lower alkyl radicals.

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Some of the Yorb'Induügea invention may according to the following 12 to reaction scheme are prepared:

COOR

COOR

Reaction scheme B

COOR

C00R7 ,.

SR ¹³ COOH

COOH

/ COOH

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O = S = O

S = O

11

. - 1ο -

In the above formulas, "Halo", R ^. R ' ⁰ and R ¹¹

■ jp
the above meaning, while R "is an alkyl or alkoxy

rest. with 6 to 12 carbon atoms and R ^ a lower one Represent alkyl radical.

5- ·

The 5-alkyl or alkoxy-7-lower-alkylthio compounds

(9) and the corresponding 5-lower-alkylthio-7-alkyl or -alkoxy compounds (15) according to schemes A and B as described in the main patent and the examples below. Then the relevant products to the sulfinyl and sulfonyl compounds (1,2) and (-3,4) oxidized, und.zv / ar directly or via the esters (io) and (15), as also from the main patent and the following Examples can be seen.

Reaction Scheraa A *

The compounds of the formula (2 ¹ ) can also be obtained according to the following reaction scheme:

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-COOR ⁷ 'R ⁹ S>

COOH

(20a)

71 11

COOR 'R-

COOR (21a)

7 ¹

COOR

. (21)

5 0 9 8 2 9/0988

JL ^ ·

7 O 10 1] In the above formulas, R, R, R and R have the

7 '
meaning given in the foregoing, R denotes hydrogen or

1 * 1
is a lower alkyl radical and R is an alkyl radical with 1 to

Carbon atoms.

Reaction scheme B ¹

The compounds of the formula (*! ') Can also according to the following Reaction scheme can be prepared:

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• V J

ALCOX (22)

COOH

(23)

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In the above formulas, R, R, R "and R ^ have the obi-

15th

ge meaning, while R is an alkyl radical having 1 to 12 carbon atoms represents.

According to schemes A 'and B ¹ , the 5-alkoxy-7-lower alkylthio-carboxylic acids or their esters (16) and the 5-lower-alkylthio-7-methoxycarboxylic acids or their esters (22), preferably the methoxy compounds, by treatment with iodine or hydrobromic acid in the presence of a suitable solvent, e.g. acetic anhydride, acetic acid or propionic acid, converted into the corresponding 5-hydroxy-7-lower alkylthio-carboxylic acids (17) and 5-lower alkylthio-7-hydroxy-carboxylic acids (23).

If desired, the compounds of the formula (17) and (23) are then esterified with an alkyl halide, for example methyl iodide, ethyl bromide or the like, in the presence of an organic solvent such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone or the like, and lithium carbonate, whereby the esters of formulas (18) and (24) are obtained. . ,

The 5-hydroxy-7-lower alkylthio-carboxylic acids (17) or their esters (18) and the 5-lower alkylthio-7-hydroxy-carboxylic acids (23) or their esters (24) are treated with an alkyl halide, preferably an alkyl bromide, for example ethyl bromide , 2-bron; propane (isopropyl bromide), 1-bromobutane (n-butyl bromide), l-bromo-3-methyl- butane (isopentyibromide), 1-bromohexane, (hexyl bromide), 1-bromo. 5 09829/09 8 8

"'· BAD ORIGINAL

. . ₁₅ -

heptane (heptyl bromide), 2-bromoheptane, 1-bromooctane (octyl bromide, 1-bromododecane (dodecyl bromide), 2-bromododecane or the like., in the presence of an organic solvent such as dimethylformamide, dimethylacetamide, acetone or the like, and potassium carbonate etherified with formation of the 5-alkoxy-7-lower alkylthio compounds (19) or the 5-lower alkylthio-7-alkoxy compounds (25)

The compounds of the formulas (19) and (25) are oxidized as described in the main patent to give the sulfonyl compounds (20) and (26) or sulfonyl compounds (21) and (27). The esters of the formulas (2O) ₃ (26), (21) and (27) are then, if desired, subjected to the basic hydrolysis also described in the main patent, the 5-alkoxy-7-lower alkylsulphinylcarboxylic acids and the 5-lower alkylsulphinyl-7 alkoxycarboxylic acids and the 5-alkoxy-7-lower alkylsulfonyl carboxylic acids and the 5-lower alkylsulfonyl-7-alkoxycarboxylic acids. Free carboxylic acids of the formula (20), (21), (26) and (27) are, if desired, converted into their salts, esters and amides, as is described further below.

But you can also use the 5-hydroxy-7- lower alkylthio compounds (17) and (18) and the 5-lower alkylthio-7-hydroxy compounds (23) and (2k) first to give corresponding sulfonyl compounds of the formulas (20a) and (26a) and sulfonyl -

509 8 29/0988 .-

• ■■ 2A61059.

Compounds of formula (21a); and (27a) oxidize according to the methods described in earlier Application No. ...... The compounds of the formulas (20a), (26a), (2Ia) and (27a) are then, as described above for the implementation from (18) to (19) and from (2 * 1) to (25) , etherified with an alkyl halide to the compounds (20), (.26) \ - _s (21) and (27). For each of the intermediates (19), (20a), (21a), (25), (26a) and (27a), a free carboxylic acid, as already mentioned, can be esterified and an ester, as already mentioned, can be hydrolyzed to the free carboxylic acid.

The o-alkyl or o-alkoxy-p-alkylthiophenol starting compounds, i.e. the compounds of formula (6) are conveniently prepared by adding the corresponding o-alkyl or o-alkoxyphenol with chlorosulfonic acid in chloroform treated, followed by reduction with zinc HCl in acetic acid and subsequent alkylation, as in the Hauft patent described, or by adding an o-alkyl or o-alkoxyphenol treated with dialkyl sulfoxide and gaseous hydrogen chloride to form the corresponding 3-alkyl or 3-alkoxy-Jj-hydroxybenzene-dialkylsulfonium chloride. The latter compound gives the corresponding o-alkyl- or o-alkoxy-p-alkylthiophenol on heating.

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That for the production of the o-alkyl compounds, for example o-Alkylphenol used by Pormel (6) is obtained by one phenol with an alkanoyl chloride (e.g. n-ectanoyl chloride) treated to form the corresponding alkanoic acid phenyl ester (e.g. phenyl-n-octanoate), which is then treated with aluminum chloride is implemented at 15o ° C, predominantly the o-alkanoylphenol (e.g. o-n-octanoyl-phenol), which. of any p-isomer present by steam distillation can be released. The o-alkanoylphenol (e.g.. o-n-Octanoylphenql), then with zinc amalgam / hydrochloric acid reduced to ο-alkylphenol (e.g. o-n-octylphenol).

The corresponding o-alkylthio-p-alkyl or p-alkoxy-phenol starting compounds, i.e. the compounds (11) are obtained by reacting a p-alkyl- or p-alkoxyphenol with chlorosulfonic acid treated and then reduced and alkylated as described above.

The p-alkylphenol used as starting material for the preparation of the p-alkyl compounds, for example of the formula (11), is obtained by reacting phenol with an alkanoyl chloride. (eg n-octanoyl) for Alkansäurephenylester (eg, phenyl-n-octanoate) is reacted, which is then reacted with Aluminiumehlorid at 25 ⁰ C and in the presence of nitrobenzene to give mainly the p-Alkanoylphenol (e.g., B. pn-octanoyl phenol), which can be freed from the o-isomer by water vapor distillation. The p-alkanoylphenol (eg pn-octanoylphenol) is then reduced with zinc amalgam / hydrochloric acid to form the p- ■ alkylphenol (eg pm-octylphenol).

The esters of the xanthone-2-carboxylic acids according to the invention are prepared according to the specification of the parent patent, ie by treating the acid with an ethereal diazoalkane such as diaso-

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methane or diazoethane, or with the corresponding lower alkyl iodide in the presence of lithium carbonate at room temperature, or with the corresponding lower alkanol in the presence of a trace of sulfuric acid at reflux temperature. the Glycerol esters are made by treating the acid with thionyl chloride, and then treating it with one suitably protected ethylene glycol or propylene glycol (e.g. Solketal) in pyridine, with subsequent hydrolysis the protective group of the ester thus formed with dilute acid.

The amides of the xanthone-2-carboxylic acids according to the invention are obtained by treating the acids with thionyl chloride and then with anhydrous ammonia, alkylamine, dialkylamine, dialkylaminoalkylamine, Treated alkoxyalkylamine or phenethylamine. The carboxamides are in the lower alkylsulfinyl series preferably in the stage of the corresponding lower alkylthio compounds generated, after which the oxidation described above is carried out.

The salts of the xanthone-2-carboxylic acids according to the invention are made by treating the acid with a pharmaceutically acceptable base. Typical examples of with The salts obtained from pharmaceutically acceptable bases are the ■ sodium, potassium, lithium, ammonium, calcium, magnesium, Iron (ll) -, iron (lII) -, zinc, iviangan (II) -, aluminum, kangan (HI), trimethylamine, triethylamine, tripropylamine, ß ~ (dimethylamino) ethanol-, triethanolamine-, ß- (diethylamino) -ethanol-, Arginine, lysine, histidine, N-ethylpiperidine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, Methylglucamine, theobromine, purine, piperazine, piperidine, Polyacin resin, caffeine and procaine salts. The formation takes place in aqueous solution in the presence or absence of an inert, water-miscible organic solvent at a temperature of about ο to about 100 ° C and preferably

509829/0988.

wise at room temperature.- Typical inert, water-miscible organic solvents are methanol, ethanol, isopropanol, butanol., acetone, dioxane or tetrahydrofuran. In the preparation of salts of divalent metals such as calcium or magnesium salts, the free acid is treated with about 1/3 mole of the pharmaceutically acceptable base -Equivalent to the pharmaceutically acceptable base.: '' -

According to a preferred embodiment of the invention the calcium and magnesium salts of the acids by treating the sodium or potassium salts with at least 1 mol equivalent Calcium chloride or magnesium chloride in aqueous solution in the presence or absence of an inert, water-miscible one organic solvent at a temperature of about 2o to about 100 ° C. ·. ·

According to a preferred embodiment * of the invention the aluminum salts by treating the acid with at least 1/3 molar equivalent of an aluminum alkoxide such as aluminum triethoxide, Aluininiuin tripropoxide or the like. In a hydrocarbon such as benzene, xylene, cyclohexane or the like. At a temperature of about 20 to about 115 ° C. shown.

In the present description and claims - referred to the term "lower alkyl" means a lower alkyl radical having from 1 to 5 carbon atoms, including straight, branched chain ones and cyclic radicals, e.g. the methyl, ethyl, n-propyl, isopropyl, η-butyl, isobutyl, sec-butyl. t-butyl, n-pentyl, isopentyl, sec-pentyl, t-pentyl, Cyclopropyl, cyclobutyl and cyclopentyl radical. Under the term "alkyl" is a higher straight chain or branched alkyl radical with 1 to 12 carbon atoms ver ■

5 09829/098 8

stood, e.g. the lower alkyl groups mentioned above and an n-hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl, isooctyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl radical or the like. Under an "alkoxy radical" is the radical "O-alkyl" is understood, in which "alkyl" has the above meaning owns.

Under the label "pharmaceutically acceptable non-toxic Esters, amides and salts "are the alkyl or glycol esters, unsubstituted, monoalkyl, dialkyl, dialkylaminoalkyl, alkoxyalkyl- or phenethyl-substituted amides and salts as defined above. - '.

In the series of the lower alkylsulfinyl compounds present a chiral center. The manufacturing processes generate d-, 1- and dl-forms, each of which is present in the frame Invention falls. If desired, the isomers, in be separated conventionally, e.g. under education . Corresponding alkaloid salts and subsequent fractional crystallization.

The nomenclature in the present description is based on Chemical Abstracts, j? 6, Subject Index (1962) January-June. For the sake of simplicity, the designation used here is intended 5 (7) -A-7 (5) -B-xanthone a mixture of 5-A-7-B-xanthone and. 5-B-7-A-xanthone mean.

The following examples illustrate the method of preparation of the compounds according to the invention. Palis required Examples were repeated to obtain sufficient starting material for the following examples.

example 1

A) A mixture of 4.138 g of 1,5-dicarbomethoxy-4-bromobensol, 3.2 g of ⁰ -n-octyl-p- (methylthio) ahenol and 1.32 g of cuprous oxide in

~ ²¹ ~ '246-059

20 ml of dimethylacetamide is heated to 160 O and under Stir and in a nitrogen atmosphere at this temperature held. As soon as the thin-layer chromatographic follow-up indicates that the reaction has essentially ended, the mixture is diluted with water and with diethyl ether / methylene chloride (3M) extracted. The extracts are ground chromatographed on 150 g of aluminum oxide and uniform fractions are combined, the 1,3-dicarbo] rίethoxy ~ 4- ^ o-n-octyl-p ~ (methyitIlio) -phenyloxy_7-benzene is obtained.

B) 4 g of 1,3 ~ dicarbomethoxy ~ 4- ^ f "o-n-octyl ~ p- (methylthio) -phenyloxyj-benzene .v / ground with 150 ml of 5% potassium hydroxide solution mixed in methanol, the mixture is refluxed for 1 hour and then acidified, cooled and filtered, where the 1,3 ~ diearboxy-4 - </ ~~ o-n-octyl-p ~ (iaethylthio) -phenyloxyy ^ -behzol receives. - "" "·.

C) 2.5 g of 1,3-dicarboxy-4- _/ / ~ on-octyl-p- (methylthio) -phenyloxyJ7 ~ benzene in 2o ml of concentrated sulfuric acid are stirred for one hour at 80 ° C, then the • reaction mixture in Pour 200 ml of ice water and heat the resulting mixture on a steam bath for 15 minutes. The mixture is then cooled and filtered, the precipitate is washed with water and then recrystallized from acetic acid. This gives the 5-n-octyl-7- (methylthio) -xanthone-

• 2-carboxylic acid. . ■. '

Example 2

A mixture of 4 g of 5-n-octyl-7- (methylthio) -xanthone-2-carboxylic acid, log methyl iodide and log lithium carbonate in 50 ml of dimethylformamide is 16 hours at room temperature touched. Thereafter, the reaction mixture is diluted in Pour hydrochloric acid / ice and the resulting mixture is

509829 / Ö98B

· ** QO ^ ^1-

extracted with ethyl acetate. The extracts wexdbn through clay filtered, the methyl 5-n-octyl-7- (sethylthio) -xanthone-2-carboxylate obtained, which can be ucikristallisiert from methanol.

Example 3

927 mg of methyl 5-n-octyl-7- (methylthio) -xanthone-2-carboxylate in 60 ml of methylene chloride are ^{cooled to 0} ° C. (ice). Then 555 rcg of m-chloroperbenzoic acid are added and the mixture is ^{stirred at 0} ° C. for 75 minutes. It is then filtered through alumina and washed with methylene chloride, giving methyl-Sn-octyl- ^ - methylsulfinylxanthone ^ -carboxylate, which can be recrystallized from benzene / heptane.

72o mg methyl S-n-octyl-T-methylsulfinylxanthone-2-csrboxylate, 75 ml of ethanol and 10 ml of 5 / aige sodium hydroxide solution are used Refluxed for 50 minutes, then the mixture is cooled, partially concentrated and acidified. The precipitation is filtered off, washed and dried, giving the 5-n-octyl-7-methylsulfinylxanthone-2-carboxylic acid, which ans acetic acid can be recrystallized.

Example 4

764 mg of methyl-5-n-octyl-7- (methylthio) -xanthon-2-carboxylate ^ ■ 2 ml 3o $ hydrogen peroxide and 40 ml. Of acetic acid is heated on a steam bath (80 ⁰ C) for 90 minutes. The thin layer chromatogram indicates the absence of starting material. The mixture is then diluted with 60 ml of hot water and cooled, the solid is filtered off and dried, the.

1 -

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246105%

7-methylsulfonylxanthone-2 ~ earboxylate is obtained, which from Acetic acid / water can be recrystallized. '.

660 mg Kethyl-5-n-octyl-7-methylsulfonyl-xanthone-2-carboxy- ' lät, 1 g of potassium hydroxide and 60 ml of 80% aqueous ethanol are refluxed for 30 minutes, then the mixture becomes filtered and acidified and the pesticide is filtered off, whereby the 5-n-octyl ~ 7-methylsulfonylxanthone-2-carboxylic acid receives. ·, · - ..: · ■

Example 5

According to the instructions A), "B) and C) of Example 1 more 5-alkyl ~ or 5-alkoxy ~ 7 ~ (nieäer-alkylthio) ~ xanthone ~ 2 ~ carboxylic acids, e.g. .. · ....- "

5-n-nexyl-7- (methylthio) -xanthone-2-carboxylic acid, ■ 5-n-Do de c "yl-7- (" methylthio) -xanthone-2-carboxylic acid, 5-n-hexyloxy 7- (methy _> lthio) -xanthone-2-carboxylic acid, 5-n-octyloxy-7- (methylthio) -xanthone-2-carboxylic acid,

• 5-.n-Dbdecyloxy-7- (methylthio) -xanthone-2-carboxylic acid and the corresponding 5-substituted compounds of- ■ 7-A'thylthio-, 7-n-propylthio, 7-isopropylthio, 7-n-butylthio, 7-isobutylthio, 7-sec-butylthio, 7-t-butylthio, 7-n-pentylthio, 7-isopentylthio and 7- (cyclopent, ylthio) -xanthone-2-carboxylic acid series manufactured. ■

The compounds obtained in this way are then converted into further 5-substituted 7-lower-alkylsulfinyl- and 7-lower-alkylsulfonyi-xanthone-2-carboxylic acids by the method of Examples 3 and 4, for example into the 5-n-hexyl 7-ethylsulfinylxanthone-2-carboxylic acid _J • 5-n-hexyl-7-ethylsulfonylxanthone-2-carboxylic acid, 5-n-r′odecyl-7-methylsulfinylxarithone-2-carboxylic acid, 5-n-! Dodecyl-7- inethylsulfonylxanthone-2 ~ carboxylic acid -usv /.,

509829/09 8 8. . ; /

5-n-Hexyloxy-7-ynethylsulfinylxanthone-2-carbnn? Acid, 5-n-Hexyloxy-7-methylsulfonylxanthone ~ 2-carboxylic acid, 5-n-Octyloxy ~ 7 ~ methylsulfinylxanthone-2-carboxylic acid, fj-n-Octyloxy - ^ - methylsulfonylxanthone-2-carboxylic acid, 5 ~ n -]) odecyloxy-7-methylsulfinylxanthone-2-carboxylic acid, 5-n-dodecyloxy-7-methylsulfonylxanthone-2-carboxylic acid, etc., 5-n-hexyl-7-ethylsulfinylxanthone-2-carboxylic acid, 5-n-hexyl ~ 7-ethylsulfonylxanthone-2-carboxylic acid, 5 ~ n-Octyl-7-ethylsulfinylxanthone-2-carboxylic acid,

5-n-octyl-7-ethylsulfonylxanthone-2-carboxylic acid, 5-n-dodecyl-7-ethylsulfinylxanthone-2-carboxylic acid,. 5 ~ n-Dodecyl-7-ethylsulfonylxanthone-2-carboxylic acid etc., 5-n-hexyloxy-7-ethylsulfinylxanthone-2-carboxylic acid, ' 5 ~ n-hexyloxy-7-ethylsulfinylxanthone-2-carboxylic acid, 5 ~ n-octyloxy-7-ethylsulfinylxanthone-2-carboxylic acid, 5 ~ n-Üctyloxy-7-ethylsulfonylxanthone-2-carboxylic acid, 5-n-I) odecyloxy-7-ethylsulfinylxanthone-2-carboxylic acid, 5-n-Podecyloxy-7-ethylsulfonylxanthone-2-carboxylic acid etc., 5-n-hexyl-7-n-propylsulfinylxanthone-2-carboxylic acid, 5-n-hexyl-7-n-propylsulfonylxanthone-2-carboxylic acid, • 5 ~ n-Octyl-7-propylsulfinylxanthone-2-carboxylic acid, 5 ~ n-octyl-7-n-propylsulfonylxanthone-2-carboxylic acid, 5-n-I) odecyl-7-n "propylsulfinylxanthone-2-carboxylic acid, 5-n-dodecyl-7-n-pro.pylsulfonylxanthone-2-carboxylic acid etc ,, 5-n-hexyloxy-7-n-propylsulfinylxanthone-2-carboxylic acid, 5Hi ~ bexyloxy-7 ~ n-propylsul, fonylxanthone-2-carboxylic acid, 5_n_Octyloxy-7-n-propylsulfinylxanthone-2-carboxylic acid, 5 ~ n-octyloxy-7-n-propylsulfonylxanthone-2-carboxylic acid, S-n-Dodecyloxy - ^ - n-propylsulfinylxanthone-2-carboxylic acid, 5-n-Dodecyloxy-7-n-propylsulfonylxanthone-2-carboxylic acid etcv, 5-n-hexyl-7-isopropylsulfinylxanthone-2-carboxylic acid, 5-H-hexyl-7-isopropylsulfonylxanthone-2-carboxylic acid, 5-n-octyl-7'-isopropylsulfinylxanthone-2-carboxylic acid, 5-n-octyl-7-isopropylsulfonylxanthone-2-carboxylic acid, 5-n-dodecyl-7-isopropylsulfinylxanthone-2-carboxylic acid, 5-n-dodecyl-7-isopropylsulfonylxanthone-2-carboxylic acid, etc.,

509829/0988

5-n-hexyloxy-7-iQoprapylsulfinylxar ^'); hcn-2-ear bonsäure, 5-n - hexyloxy-7-isopropylsulf onylxanthon-2-carboxylic acid, _n _Üctyloxy 5_-7-isopropylsulf inylxa.nthonr carbonßäure-2-, 5_N-octyloxy-7-isopropylsulfonylxanthon earbonsäure-2, 5-n-dodecyloxy-7-isqpropylsulfinylxanthon-2-carboxylic acid, _n -.Dodecyloxy 5_-7-isopropyisulfOnylxanthon-2-carbönsäure etc.

Example 6

Example 5 v / ill be repeatedly for the purpose of production of the following 5 ~ · (lower Allc5 ^r lthio) -7-alkyl- / alkoxy xant hon-2-carb.onsäuren the corresponding sulfinyl and Sulfotiylverbindungen: 5-methylthio-7-n- hexylxanthone-2-carboxylic acid, 5-methylthio-7-n-octylxanthone-2-carboxylic acid, 5 * -] viethylthio-7-n-do.de _i cylxanthori-2-carboxylic acid etc., 5-methylthio-7-n- hexyloxyxanthone-2-carboxylic acid, 5-methylthio-7-n-octyloxyxanthone-2 "-carboxylic acid, 5-methylthio-7-n-dodecyloxyxanthone-2-carboxylic acid, etc., the corresponding compounds of 5-ethylthio, 5-n- Propyl, 5-n-propylthio, 5-isopropylthio series, etc., 5-methylsulfinyl-7-n-hexylxanthone-2-carboxylic acid, 5-methylsulfonyi-7-n-hexylxanthone-2-carboxylic acid, 5-methylsulfinyl-7 -n-octylxanthone-2-carboxylic acid, 5-methylsulfonyl-7-n-octylxanthone-2-carboxylic acid,.

5-Kethylsulflnyl-7-n-dodecylxanthone-2-carboxylic acid, 5-methylsulfonyl ~ 7-n.-dodecylxanthone-2-carboxylic acid,:

5-methylsulfinyl-7-n.-hexyloxyxanthone-2-carboxylic acid, 5-methylsulfonyl-7-n-hexyloxyxanthone-2-carboxylic acid, ''

5-ethylsulfinyl-7-n-octyloxyxanthone-2-carboxylic acid, 5-ethylsulfonyl-7-n-octyloxyxanthone-2-carboxylic acid, 5-methylsulfinyl-7-n-dodecyloxyxanthone-2-carboxylic acid, 5-methylsulfonyl-7-n- dodecyloxyxanthone-2-carboxylic acid etc., 5-ethylsulfin3 ^r l-7-n-hexylxanthone-2-carboxylic acid, 5-ethylsulfonyl-7-n-hexylxanthoh-2-carboxylic acid,

509829/0988 Λ. ·· /

5-ethylsulfinyl-7-n ~ octylxanthone-2-carboxylic acid, 5-ethylsulfonyl-7-n-octylxanthone-2-carboxylic acid, 5-ethylsulfinyl-7-n-dodecylxanthone-2-carboxylic acid, 5-ethylsulfonyl-7-n-dodecylxanthone-2- carboxylic acid etc., 5-ethylsulfinyl-7-n "hexyloxyxanthone-2-carboxylic acid, 5-ethylsulfonyl-7 ~ n-hexyloxyxanthone-2-carboxylic acid, 5-ethylsulfinyl-7-n-octyloxyxanthone-2-carboxylic acid, 5-ethylsulfonyl-7-n-octyloxyxanthone-2-carboxylic acid, 5-ethylsulfonyl-7-n-dodecyloxyxanthone-2-carboxylic acid, 5-ethylsulfonyl-7-n-dodecyloxyxanthone-2-carboxylic acid, etc., 5-n-propylsulfinyl-7-n-hexylxanthone-2-carboxylic acid, 5-n-propylsulfonyl-7-n-hexylxanthone-2-carboxylic acid, 5-n-Propylsulfynyl-7-n-o c ty lxanthano'n-2-carboxylic acid, 5-n-propylsulfonyl-7-n-octylxanthone ~ 2-carboxylic acid, 5-n-propylsulfinyl-7-n-dodecylxanthone-2-carboxylic acid, 5-n-propylsulfonyl-7-n-dodecylxanthone-2-carboxylic acid, etc., 5-n-propylsulfinyl-7-n-hexyloxyxanthone-2-carboxylic acid, 5-n-propylsulfonyl-7-n ~ hexyloxyxanthone-2-carboxylic acid, 5-n-propylsulfinyl-7-n-octyloxyxanthone-2-carboxylic acid, 5-n-propylsulfonyl-7-n-octyloxyxanthone-2-carboxylic acid, 5-n-propylsulfinyl-7-n-dodecyloxyxanthone-2-carboxylic acid, 5-n-propylsulfonyl-7-n-dodecyloxyxanthone-2-carboxylic acid, etc., 5-Isopropylsulfinyi-7-n-hexylxanthone-2-carboxylic acid, S-Isopropylsulfonyl ^ -n-hexylxanthone - ^ - carboxylic acid, 5-isopropylsulfinyl-7-n-octyixanthone-2-carboxylic acid, 5-isopropylsulfonyl-7-n-octylxanthone-2-carboxylic acid, 5-isopropylsulfinyl-7-n-dodecylxanthone-2-carboxylic acid, 5-Isopropylsulfonyl-7-n-dodecylxanthone-2- carboxylic acid etc., 5-isopropylsulfinyl-7-n-hexyloxyxanthone-2-carboxylic acid, 5-isopropylsulfonyl-7-n-hexyloxyxanthone-2-carboxylic acid, 5-isopropylsulf inyl ^ -n-octyloxyxanthone ^ -carboxylic acid, 5-isopropylsulfonyl-7-n-octyloxyxanthone-2-carboxylic acid, 5-isopropylsulfinyl-7-n-dodecyloxyxanthone-2-carboxylic acid, 5-isopropylsulfonyl-7-n-dodecyloxyxanthone-2-carboxylic acid, etc.

509829/098 8

Example 7

A suspension of 500 mg of 5-hydroxy-7-methylthio-xanthone-2-carboxylic acid methyl ester (prepared as "in Example 11, Part B) in 20 ml of dimethylformamide is a solution of 320 mg of m-chloroperbenzoic acid in 3 rol -dimethylformamide dropwise "added at room temperature. After stirring for 15 minutes, 50 ml of a 1 # aqueous sodium bisulfite solution are added and the precipitate formed is filtered off and washed with water and then with acetone. In this way, 480 mg of 5-hydroxy-7-methylsulfinyl-xanthone-2-carboxylic acid methyl ester with a melting point of 289 ° -291 ° C. (decomp.) Are obtained. ^:

The methyl 5-hydroxy-7-methylthio-xanthone-2-carbonate is replaced by the 5 ^ methylthio-7 ~ hydroxyxanthone-2-5carboxylic acid methyl ester (prepared in Example 11, Part B) and operating in a similar manner to obtain one the 5-methylsulfinyl-7-hy ■ droxy-xanthΌn-2-carboxylic acid methyl ester of m.p. 322-323 ° C (dec.). ',

If you replace the above-mentioned starting products by other lower alkyl esters or by the corresponding free 2-carboxylic acids, the following compounds are prepared: 5-Hydroxy-7-methylsulfinyl-xanthone-2-. carboxylic acid, 5-hydroxy-7-methylsulfinylxanthone-2-carboxylic acid ethyl ester, 5-Hydroxy-7-methylsulfinylxanthone-2-carboxylic acid pentyl ester, 5-methylsulfinyl-7-hydroxyxanthone-2-carboxylic acid,

5098 29/098 8

■ 5-methylsulfinyl-7-hydroxyxanthone-2-carboxylic acid ethyl ester and 5-methylsulfinyl-7-hydroxyxanthone-2-cart) acid pentyl ester.

If the methylthio starting materials mentioned above are replaced in a similar manner by the corresponding starting materials, the ethylsulfinyl, propylsulfinyl, butylsulfinyl and pentylsulfinyl compounds are obtained.

Example 8

If you start from 5-hydroxy-7-methylthioxanthone-2-carboxylic acid, 5-methylthio-7-hydroxyxanthone-2-carboxylic acid or a lower alkyl ester thereof and oxidize. in a manner similar to that described in example k , the following compounds can be prepared: 5-hydroxy-7-methylsulfonylxanthone-2-carboxylic acid, 5-hydroxy-7-methylsulfonylxanthone-2-carboxylic acid methyl ester, 5-hydroxy-7 -methylsulfonylxanthone-2-carboxylic acid pentyl ester, 5-methylsulfonyl-7-hydroxyxanthone-2-carboxylic acid, 5-methylsulfonyl-7-hydroxyxanthone-2-carboxylic acid methyl ester and
5-methylsulfonyl-7-hydroxyxanthone-2-carboxylic acid pentyl ester.

If you replace the above-mentioned methylthio starting

so

products through other lower alkylthio starting products77 the corresponding ethylsulfonyl, propylsulfonyl,

Butylsulphonyl and pentylsulphonyl compounds produced “earth. 509829/0988

Example 9

Starting with the appropriate 5 (7) hydroxy-7 (5) lower alkylsulfin-yl compounds of Example 7 and carrying out the alkylation according to the procedure of Example 11, Part Cj using an appropriate alkyl halide having 1 to 12 carbon atoms and if a carboxylic acid ester obtained is hydrolyzed, if appropriate, by the process of Example 11, Part F, the following compounds can be prepared:
5-methoxy-7-methylsulfinylxanthone-2-carboxylic acid, 5-methoxy-7-methylsulfinylxanthone-2-carboxylic acid methyl ester, 5-methoxy-7-methylsulfinylxanthone-2-carboxylic acid pentyl ester, 5-ethoxy-7-methylsulfinylxanthone-2 ~ carboxylic acid, m.p. 273-

5 ~ ethoxy ~ 7-methylsulfinylxanthone-2-carboxylic acid methyl ester, 5-ethoxy-7-methylsulfinylxanthone-2-carboxylic acid pentyl ester, 5-propoxy-7-methylsulfinylxanthone-2-carboxylic acid, m.p. 265-267 ° C, -

S-propoxy ^ -methylsulfinylxanthone ^ -carboxylic acid methyl ester, 5-propoxy-7-methylsulfinylxanthone-2-carboxylic acid pentyl ester, 5-Isopropoxy-7-methylsulfinylxanthone-2-carboxylic acid, m.p. 280-282 ° C,

5-isopropoxy-7-methylsulfinylxanthone-2-carboxylic acid methyl ester, >. . -

5-Isopropoxy-7-methylsulfinylxant ^

509829/0988

ester,

S-Butoxy ^ -methylsulfinylxanthone ^ -carboxylic acid, m.p. 269-270 ° c,.

S-Butoxy ^ -methylsulfinylxanthone ^ -carboxylic acid methyl ester, 5-butoxy-7-methylsulfinylxanthone-2-carboxylic acid pentyl ester, 5-pentoxy-7-methylsulfinylxanthone-2-carboxylic acid, m.p. 263-265 ° C,. ^:

5 ~ pentoxy-7-methylsulfinyl.xanthone-2-carboxylic acid methyl ester, 5-pentoxy-7-methylsulfinylxanthone-2-carboxylic acid pentyl ester _> 5-isopentoxy-7-methylsulfinylxanthone-2-carboxylic acid _J mp.

271-273 ° c,. .

5-Isopentoxy-7-methylsulfinylxanthone-2-carboxylic acid methyl ~

ester,
5-Isopentoxy-7-methylsulfinylxanthone-2-carboxylic acid pentyl ester

5-octyloxy-7-methylsulfinylxanthon-carboxylic acid 2-, mp. 258-260 ⁰ C.

S-Octyloxy ^ -methylsulfinylxanthone ^ -carboxylic acid methyl ester, . 5-octyloxy-7-methylsuliinylxanthone-2-carboxylic acid-pentyl-

ester,.

5-dodecyloxy-7-methylsulfinylxanthone-2-carboxylic acid, m.p.

254-255 ° C,

5-dodecyloxy-7-methylsulfinylxanthone-2-carboxylic acid methyl ester, 5-dodecyloxy-7-methylsulfinyixanthone-2-carboxylic acid pentyl

ester,
. ·

509829/0988

- 3i -

and the corresponding 7-Aethylsulfinyl-, propylsulfinyl, 'butylsulfinyl and Pentylsuifinyl compounds, and ⁱ 5- methylsulfinyl-7-methoxyxanthone-2-carboxylic acid ,. S-methylsulfinyl ^ -methoxyxanthone ^ -carboxylic acid methyl ester, 5-methylsulfinyl-7-methoxyxanthone-2-carboxylic acid pentyl ester, 5-methylsulfinyl-7-ethoxyxanthone-2-carboxylic acid, 5-methylsulfinyl-7-ethoxyxanthone-2-carboxylic acid methyl ester, 5-methylsulfinyl-7-ethoxyxanthone-2-carboxylic acid pentyl ester _ί 5-methylsulfinyl-7-propoxyxanthone-2-carboxylic acid, 5-methylsulfinyl-7-propoxyxanthone-2-carboxylic acid methyl ester, 5-methylsulfinyl-7-propoxyxanthone 2-carboxylic acid pentyl ester ₃ S-methylsulfinyl ^ -isopropoxyxanthone - ^ - carboxylic acid, m.p.

276-278 ° c _s

5-methylsulfinyl-7-isopropoxyxanthone-2-carboxylic acid methyl ester,

5-methylsulfinyl-7-isopropoxyxanthone-2-carboxylic acid pentyl ~ ester,. ·

S-methylsulfinyl - ^ - butoxyxanthone - ^ - carboxylic acid, 5-methylsulfinyl-7-butoxyxanthone-2-carboxylic acid methyl ester _a 5-methylsulfinyl-7-butoxyxanthone-2-carboxylic acid pentyl ester ₃ 5 ~ methylsulfinyl-7-pentoxyxanthone-2- carboxylic acid, m.p. 2 * 12-2M ⁰ C ,. ■.

.'5-Methylsulfinyl-7-pentoxyxanthone-2-carboxylic acid methylR3ter _a 5-methylsulfinyl-7-pentoxyxanthone-2-carboxylic acid pentyl ester; 5-methylsulfinyl-7-isopentoxyxanthone-2-carboxylic acid _a

509829/0988

* '- 32 -

S-methylsulfinyl ^ -isopentoxyxanthone ^ -carboxylic acid methyl ester,

5-methylsulfinyl-7-isopentoxyxanthone-2-carboxylic acid pentyl ester, '.

S-methylsulfinyl-T-octyloxyxanthone - ^ - carboxylic acid, m.p.

219 ° C,. . .

5-methylsulfinyl-7-octylcxyxanthone-2-carboxylic acid methyl ester _J S-methylsulfinyl-T-octyloxyxanthone - ^ - carboxylic acid pentyl ester, 5-methylsulfinyl-T-dodecyloxyxanthone - ^ - carboxylic acid, m.p.

196-197 ° c,

S-methylsulfinyl ^ -dodecyloxyxanthone ^ -carboxylic acid-methyl-

ester,.

5 ~ MethyIs-Ifiny1-7-dodecyloxyxanthone-2-carboxylic acid-pentyl-

and the corresponding 5-ethylsulfinyl, propylsulfinyl, Butylsulfinyl and pentylsulfinyl compounds.

Example 10

Starting from the suitable 5 (7) -hydroxy-7 (5) -lower alkylsulfonyl compounds of Example 8 _} the alkylation is carried out by the method of Example 11, Part C, using a suitable alkyl halide having 1 to 12 carbon atoms through and hydrolyzed, if desired, a carboxylic acid ester obtained by the method of Rcinpiol T! . Part 3 P- so the following-

509829/0988,

- · .3 3 ~ -

the connections are made:

S-methoxy ^ -methylsulfonylxanthone ^ -carboxylic acid, S-methoxy ^ -methylsulfonylxanthone ^ -carboxylic acid methyl ester, t-methoxy-7-methylsulfonyixanthone ~ 2-carboxylic acid pentyl ester, 5-ethoxy-7-methylsulfonylxanthone-2-carboxylic acid, 5- ethoxy-7-methylsulfonylxanthon-2-carboxylic acid methylester, 5-ethoxy-7-methylsulfonylxanthon-2-carboxylic acid pentyl ester _i 5-propoxy-7-methylsulfonylxanthon-2-carboxylic acid ;, 5-propoxy-7-πlethyl _S ulfonylxanthon-2 -carboxylic acid methyl ester, 5-propoxy-7-methylsulfonylxanthone-2-carboxylic acid pentyl ester, 5-isopropoxy-7-methylsulfonylxanthone-2-carboxylic acid, m.p.

318 ⁰ C, ...

5-isopropoxy-7-methylsulfonylxanthone-2-carboxylic acid methyl ester,

5-isopropoxy-7-methylsulfonylxanthone-2-carboxylic acid pentyl ester,

5-butoxy-7-methylsulfonylxanthone-2-carboxylic acid, 5-butoxy-7-methylsulfonylxanthone-2-carboxylic acid methyl ester, 5-butoxy-7-methylsulfonylxanthone-2-carboxylic acid pentyl ester _> 5-pentoxy-7-methylsulfonylxanthone-2- carboxylic acid, 5-pentoxy-7-methylsulfonylxanthone-2-carboxylic acid methyl ester, 5-pentoxy-7-methylsulfonylxanthone-2-carboxylic acid pentyl ester ₃ 5-isopentoxy-7-methylsulfonylxanthone-2-carboxylic acid, 5-isopentoxy-7 -methylsulfonyixanthone-2-carboxylic acid-methy1-

ester,. "

509829/0988. - -

5 ~ isopentoxymethylsulfonylxanthone-2-carboxylic acid-pentyl-

ester,

5-octyloxy-7-methy1sulfonylxanthone-2-carboxylic acid, 5-Octyloxy ~ 7-methylsulfonylxanthone-2-carboxylic acid-methy1-

ester,.

5-Octyloxy-7-methylsulfonylxanthone-2-carboxylic acid pentyl ester,

5-dodecyloxy-7-methy1sulfonylxanthon-2-carboxylic acid, 5-dodecyloxy-7-met hy lsulfony lxanthon.-2-carboxylic acid-met hy _1-esters:

5-dodecyloxy-7-methylsulfonylxanthone-2-carboxylic acid pentyl ester, . .

and the corresponding 7-ethylsulfonyl, propylsulfonyl, .Butylsulfonyl and pentylsulfonyl compounds, and 5-methylsulfonyl-7-methoxyxanthone-2-carboxylic acid, 5-Methylsulfony1-7-methoxyxanthone-2-carboxylic acid methyl ester, 5-Methylsulfony1-7-methoxyxanthone-2-carboxylic acid pentyl ester, 5-methylsulfonyl-7-ethoxyxanthone-2-carboxylic acid, 5-methylsulfonyl-7-ethoxyxanthone-2-carboxylic acid methyl ester, 5-methylsulfonyl-7-ethoxyxanthone-2-carboxylic acid pentyl ester, 5-methylsulfonyl-7-propoxyxanthone-2-carboxylic acid, 5-methylsulfony1-7-propoxyxanthone-2-carboxylic acid methyl ester, 5-methylsulfony1-7-propoxyxanthone-2-carboxylic acid pentyl ester, 5-methylsulfonyl-7-isopropoxyxanthone-2-carboxylic acid, m.p.

308-309 ^Q c,

50 9829 / Q988

5-methylsulfonyl-7-isopropoxyxanthone-2-carboxylic acid methyl ester,

5-methylsulfonyl-7-isopropoxyxanthone ^ -carboxylic acid-pentyl-

ester,.

5-methylsulfonyl-7-butoxyxanthone ^ -carboxylic acid ,.

5-methylsulfonyl-7-b ■ utoxyxanthone-2-carboxylic acid methyl ester, 5-methylsulfonyl-7-butoxyxanthone-2-carboxylic acid pentyl ester _s 5-methylsulfony1-7-pentoxyxanthone-2-carboxylic acid,

5-methylsulfonyl-7-pentoxyxanthone-2-carboxylic acid methyl ester j 5-methylsulfony1-7-pentoxyxanthone-2-carboxylic acid pentyl ester, 5-methylsulfonyl-7-isopentoxyxanthone-2-carboxylic acid,

5- ■ i ^v ethylsulfonyl-7-isopentoxyxanthone-2-carboxylic acid methyl ester,

5-methylsulfony1-7-isopentoxyxanthone-2-carboxylic acid pentyl - ester,

^ -Methylsulfonyl ^ -octyloxyxanthone ^ -carboxylic acid,

5-methylsulfonyl-7-octyloxyxanthone-2-carboxylic acid-methyl-

ester, -

5-methylsulfonyl-7-octyloxyxanthone-2-carboxylic acid pentyl ester, 5 ~ methylsulfonyl-7-dodecyloxyxanthone-2-carboxylic acid,

5-methylsulfonyl-7-dodecyloxyxanthone-2-carboxylic acid methyl ester,

5 ~ methylsulfonyl-7-dodecyloxyxanthone-2-carboxylic acid-pentyl'-

ester, * '

and the corresponding 5-ethylsulfonyl-. Propylsulfony] -,

• 50 9 82 9 / Ό988

Butylsulfonyl and pentylsulfonyl compounds.

Example 11

A) To a suspension of 1 * 1.5 g of 5-methoxy-7- (methylthio) xanthone-2-carboxylic acid 100 ml of 47% hydroiodic acid in 350 ml of acetic anhydride are added dropwise while cooling with ice. After refluxing for 20 hours, the mixture is diluted with 750 ml of hot water and cooled. The yellow The product is filtered off, washed with water and dried, 12.8 g of 5-hydroxy-7- (methylthio) -xanthene-2-carboxylic acid being obtained receives. .

The 5-methoxy-7- (methylthio) -xanthone-2-carboxylic acid is replaced by 5-methylthio-7-methoxyxanthone-2-carboxylic acid, the 5-methyl-thio-7-hydroxyxanthone-2- carboxylic acid obtained.

In the same way, other 5-hydroxy-7- (lower-alkylthio) -xanthone-2-carboxylic acids and 5-lower-alkylthio-7-hydroxyxanthone-2-carboxylic acids are obtained.

B) i A mixture of 6.65 g of 5- ⁱ ~ ydroxy 7- (methylthio) -xanthon-2-carboxylic acid, 4.5 g of dry lithium carbonate, 4 ml of methyl iodide and Jo ml of dimethylformamide is stirred 2o hours at room temperature. After adding an excess of acetic acid and water (1: 1), excess methyl iodide is removed on a rotary evaporator. The crystalline product is filtered off, washed and dried to give 6 g ^ 8-methyl-5-hydroxy-7- (methylthio) -xanthon-2-carboxylate, mp. 286 ⁰ C (dec.) Is obtained.

If one uses the S-methylthio - ^ - hydroxyxanthone " 2-carboxylic acid, the methyl ~ 5-methylthio-7-hydroxyxanthone-2-caroxylate is of m.p. 290 C (decomp.) obtained.

509829/0988 ■

The above process is repeated with other lower alkyl iodides for the purpose of "preparing the lower alkyl esters, e.g. of ethyl 5-hydroxy-7- (methylthio) -xanthone-2-carboxylate, Pentyl 5-hydroxy-7- (methylthio) -xanthone-2-carboxylate and ethyl 5-methylthio-7-hydroxyxanthone-2-carboxylate and pentyl ^ -methylthio - ^ - hydroxyxanthone - ^ - carboxylate.

C) 1.55 g of methyl 5-hydroxy-7- (methylthio) -xanthone-2-carboxylate are at room temperature with 2.5 g of octyl bromide and 1, o g Potassium carbonate in 3o ml of dimethylformamide was stirred for 18 hours. The mixture is acidified with dilute hydrochloric acid extracted with chloroform, the extracts are washed with water, dried over magnesium sulfate and concentrated. When filtering the chloroform solution of the crude product through Clay (activity II) gave 2.0 g of methyl 5-n-octyloxy-7- (methylthio) -xanthori-2-carboxylate.

If the above procedure is repeated with methyl 5-methylthio-7-hydroxyxanthone-2-carboxylate, so the .Methyl - ^ - methylthio-T-n-octyloxyxanthone ^ -carboxylate is obtained.

The above procedure is repeated using other higher alkyl bromides for the purpose of preparing the corresponding 5- and 7-higher alkoxy compounds, e.g. . Methyl 5-n-hexyloxy-7- (methylthio) -xanthone-2-carboxylate, Methyl 5-n-heptyloxy-7 - '(methylthio) ~ xanthone-2-carboxylate, Methyl 5-n-dodecyloxy-7 ~ (methylthio) -xanthone-2-carboxylate, and

Methyl-S-methylthio ^ -n-hexyloxyxanthone ^ -carboxylate, Methyl 5-methylthio-7-n ~ heptyloxyxanthone-2-carboxylate and Methyl ^ -methylthio ^ -n-dodecyloxyxanthone ^ -carboxylate. You can also replace the methyl ester with other lower alkyl esters, which is what you get when using the. appropriate higher alkyl bonds see B. the connections

50 9 8 29/0988

Ethyl-Sn-octyloxy-T- (methyIthio) -xanthone-2-carboxylate, pentyl-5-n-octyloxy-7- (methylthio) -xanthone-2-carboxylate _, ethyl-5-n-hexyloxy-7 ~ (methylthio ) -xanthone-2-carboxylate, perityl-5-n-heptyloxy-7- (methylthio) -xanthone-2-carboxylate, ethyl-5-n-dodecyloxy-7- (methylthio) -xaathon-2-carboxylate, ethyl S-methylthio ^ -n-octyloxyxanthone ^ -carboxylate, pentyl ^ -methylthio ^ -n-octyloxyxanthone - ^ - carboxylate, ethyl S-methylthio ^ -n-hexyloxyxanthone ^ -carboxylate, pentyl ~ 5-methylthio-7-n- hexyloxyxanthone-2-carboxylet and ethyl-fi-methylthio ^ -n-dodecyloxyxanthone ^ -carboxylate,

D) A solution of 9I0 mg of m-chloroperoxybenzoic acid in 40 ml of chloroform is slowly added to 2, above-mentioned methyl 5-n-octyloxy-7- (raethylthio) -xanthone-2-carboxylate in 60 ml of chloroform, the temperature being kept at holds about O ^{0 C.} After the addition is complete, the solution is replaced by clay (activity III). filtered and concentrated, 2, above-mentioned methyl 5-n-octyloxy-7-methylsulfinylxanthone-2-carboxylate being obtained.

If 5-methylthio-7-n-octyloxyxanthone-2-carboxylate is used in the above process as the starting material, methyl 5-methylsulfinyl-7-n-octyloxyxanthone-2-carboxylate is obtained.

In addition, if the 5-n-octyloxy-7- (methylthio) -xanthone-2-carboxylate is replaced by other compounds obtainable according to Part C of this example, for example the Products

Ifiethyl-5-n-hexyloxy-7-methylsulfinylxanthone- ^ - carboxylate, methyl-5-n-heptyloxy-7-methylsulfinylxanthone-2-carboxylate, methyl-5-n-dodecyloxy-7-methylsulfinylxanthone-2-carboxylate, ethyl-5 -n-octyloxy-7-methj ' ^p lsulfynylxanthone-2-carbox3 ^! "lat, Pentyi-5-n-oc tyloxy-7-methylsul'f inylxanthone-2-carboxylate, Xthyl-5-n-hexyloxy-7-methylsulphinylxanthone-2-carboxylate, pentyl-5-u-hept5 ■ loxy- 7-methylsulfiΰylxanthou-2-carbox3-lεt, and '

509829/0988

Ethyl 5-n-dodecyloxy-7-methylsulfinylxanthone-2-carboxylate,

as ,

'Methyl-5-methylsulfiüyl-7-n-hexyloxyxanthone ~ 2 ~ carboxylate, Methyl 5-methylsulfinyl-7-n-heptyloxyxantion-2-carboxylate, Methyl 5-methylsulfinyl ~ 7-n-dodecyloxyxanthone-2-carboxylate, ethyl 5-ynethylsulfinyi-7-n-octyloxyxanthone-2-carboxylate; Pentyl-5-methylsulfynyl ^ -n-octyloxyxanthone ^ -carboxylate, Ethyl-5-methylsulfinyl-7-n-hexyloxyxanthone-2-carboxylate, Pentyl 5-methylsulfinyl-7-n-hexyloxyxanthone-2-carboxylate, and '

Ethyl 5-methylsulfynyl ^ -n-dodecyloxyxanthone ^ -carboxylate.

E) 75 ° ^m S methyl 5-n-octyloxy-7- (methyltliio) -xanthone-2-carboxylate, 2 ml of 3o ^ iges hydrogen peroxide and 40 ml of acetic acid are heated on a steam bath (80 ° C) for 90 minutes. The thin-layer chromatogram shows the absence of starting material. The mixture is diluted with 60 ml of normal water and cooled, the solid is filtered off and dried, giving methyl 5-noctyloxy-7-methylsulfonylxanthone-2-carboxylate, which is recrystallized from acetic acid / water can.

In addition, the use of diethyl 5-methylthio-7-n-octyloxy-2-carboxylate is obtained in the above process the methyl 5-methylsulfonyl-7-n-9ctyloxyxanthone-2-carboxylate. ■

The methyl 5-n-octyloxy-7- (methylthio) -xanthone-2-carboxylate is also replaced by other compounds obtainable according to Iil C of this example, one obtains, for example, the Products

Methyl 5-n-hexyloxy-7-methylsulfonylxanthone-2-carboxylate, Methyl 5-n-heptyloxy-7-methylsulfonylxanthone-2-carboxylate, Methyl 5-n-dodecyloxy-7-methylsulfonylxanthone-2-carboxylate, Ethyl 5-n-octyloxy-7-methylsulfonylxanthone-2-carboxylate, Pentyl 5-n-octyloxy-7-methylsulfonylxanthone-2-carboxylate, Ethyl 5-n-hexyloxy-7-methylsulfonylxanthone-2-carboxylate, Penfyl-5-n-heptyloxy-7-methylsulfonylxanthone-2-carboxylate,

509 8 29/09 8 8

Ethyl-5-n-dodecyloxy-7-niethylsulfonylxanthone-2 ~ cartoxylot,

KIethyl-5-methylsulfonyl-7-n-hexyloxyxanthone-2-carboxylate, Methyl-S-methylsulfonyl ^ -n-heptyloxyxanthori ^ -carb.oxylat, Methyl-5 ~ methylsulfonyl-7-n-dodecyloxyxanthone-2-carboxy ^ at, Ethyl-S-methylsulfonyl ^ -n-octyloxyxanthone ^ -carboxylate, Pentyl 5-methylsulfonyl-7-n-octyloxyxanthone-2-carboxylate, Ethyl-5-methylsulfonyl-7-n-hexyl oxyxanthone-2- carboxy lat, Pentyl-5-diethylsulfonyl-7-n-hexyloxyxanthone-2-carboxylate,

Ethyl "5-methylsulfonyl-7-n-dodecyloxyxanthone-2-carboxyla" t.

P) 2.0 g of methyl 5-n-octyloxy-7-methylsulfinylxanthone-2-earboxylate 30 minutes with 0.5 g of potassium hydroxide in 80 ml of ethanol, which contains 20 ml of water, on the Kückflui3 cooked. After acidification with dilute hydrochloric acid, the precipitate is filtered off and made from tetrahydrofuran / ethanol recrystallized, 1.8 g of 5-n-octyloxy-7-methyl ~ sulfinylxanthone-2-carboxylic acid is obtained.

The diethyl 5-n-octyloxy-7-methylsulfinylxanthone-2-carboxylate is replaced by other compounds obtainable according to Part I) and E of this example, the products are obtained, for example 5-methylsulfinyl-7-n-octyloxyxanthone-2-carboxylic acid, 5-n-octyloxy-7-methylsulfonylxanthone-2-carboxylic acid, 5-methylsulfonyl ~ 7-n ~ octyloxyxanthone-2-carboxylic acid, 5-n ~ hexyloxy-7-methylsulfinylxanthone-2-carboxylic acid, 5-n-heptyloxy-7-methylsulfinylxanthone-2-carboxylic acid, 5-n-dodecyloxy ~ 7-methylsulfinylxanthone-2-carboxylic acid, 5 ~ methylsulfinyl-7-n-hexyloxyxanthone-2-carboxylic acid, 5-methylsulfinyl-7-n-heptyloxyxanthone-2-carboxylic acid,

5-methylsulfinyl-7-n-dodecyloxyxanthone-2-carboxylic acid, 5-n-Iiexyloxy-7-methylsulfonylxanthone-2-carboxylic acid, 5 ~ n-heptyloxy-7-methylsulfonylxanthone-2-carboxylic acid,,

• · 509829/0988

5-n-dodecyloxy-7-methylsulfonylxanthone-2-carboxylic acid, 5 ~ methylsulfonyl-7 ~ n-hexyloxyxanthone-2-carboxylic acid,.-Ij-methylsulfonyl ^ -n-heptyloxyxanthone ^ -carboxylic acid,

and .

5-l, iethylsulfonyl-7-n-dode.cyloxyxanthone-2-carboxylic acid.

Example 12

A mixture of 4.5 g of 5-n-octyl-7-methylsulfinylxanthone-2-carboxylic acid, 1o g of methyl iodide. and 1o g. Lithium carbonate in 75 ml of dimethylformamide is 18 hours at room temperature touched. Then the reaction mixture is poured into dilute hydrochloric acid / ice poured and the resulting precipitate is filtered off and washed, the l »; ethyl-5-n-octyl-7 · methylsulfinylxanthone-2-carboxylate is obtained.

The above procedure is carried out with other lower alkyl iodides repeated, with the corresponding lower. Alkyl ester, e.g. the

Ethyl 5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, n-propyl-5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, Isopropyl-S-n-octyl ^ -methylsulfinylxanthone-2-carboxylate, n-propyl-5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, Isobutyl 5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, 8ek-butyl-5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, n-Pentyl-5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, etc.

Other xanthone-2-carboxylic acids can do the same with substituents in 5- and 7-Stelluhg referring to the above Manner were converted into the corresponding esters Y / earth, e.g. in the

Methyl 5 ~ n-octyl-7-methylsulfonylxanthone2-carboxylate, Ethyl 5-methylsulfonyl-7-n-octylxanthone-2-carboxylate, n-propyl-5-n-octyl-7-sulf ai.ioylxanthone-2-carboxylate, Methyl 5-acetyl-7-n-octylxanthone-2-carboxylate, etc.

509829/0988

In the sulfo series, the esters are obtained by the acid is treated with the corresponding lower alkanol under reflux conditions and in the absence of acid. Examples are:

Methyl 5-n-octyl-7-sulfoxanthone-2-carboxylate and Ethyl 5-n-octyl-7-sulfoxanthone-2-carboxylate.

■ Example 13

To a solution of log 5-n-octyl-7-methylsulfinylxanthone-2-carboxylic acid the theoretical amount of sodium hydroxide dissolved in 2oo ml of 905% ethanol is added in 2oo ml of ethanol. Then the reaction mixture is concentrated in vacuo, being the sodium i ^ -n-octyl ^ -methylsulfinylxanthone-2-carboxylate receives.

The potassium and lithium salts are produced in an analogous manner. Likewise, if the sodium salt is replaced by a corresponding other metal salt, e.g. calcium chloride, Manganese chloride or the like, other salts of xanthone-2-carboxylic acids such as

Magnesium-5-n-octyl-7-methylsulfinylxanthone-2- carboxylate, Calcium 5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, Aluminum 5-n-octyl-7-methyl3ulfinylxanthone-2-carboxylate, Iron (II) -5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, Zinc 5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, Manganese 5-n-octyl-7-methylsulfinylxanthone-2-carboxylate, Iron (III) -5-n-octyl-7-methylsulfinylxanthone-2-carboxylate etc.

The salts of the other 5i7-disubstituted xanthone-2-carboxylic acids according to the invention are prepared in the same way, for example the

Potassium 5-n-octyl-7-methylsulfonylxanthone-2-carboxylate, Katriuia-5-n-hexyl-7-iueth,> 'läulfinylxant-ίοti-2-carboxylate,

5098 29/0 9-8 8

- i | 3 -

Sodium 5-n-octyloxy-7-methylsulfinylxant.hon-2-carboxylate, Sodium 5-methylsulfonyl-7-n-octyloxyxanthone ~ 2-carboxylate, Sodium 5-methylsulfinyl-7-n ~ octyloxyxanthone-2-carboxylate ,. Sodium 5-n-dodecylpxy ~ 7-ynethylsulfonylxanthone-2-carboxylate, Hatrium-5-n-dodecyloxy-7-methylsulfinylxanthone-2-carboxyla't, Sodium 5-n ~ bexyloxy-7-ynethylsulfonylxanthone - 2-carboxylate, Sodium 5-n-hexyloxy-7-methyisulfinylxanthone-2-carboxylate, Sodium 5-n-octyloxy-7-methylsulfonylxanthone-2-carboxylate ■ etc.

Example I ^

A solution of 10 g of 5-n-octyl-7-methylsulfinylxanthone-2-carboxylic acid in 50 ml of thionyl chloride is refluxed for 1 hour. The solution is then concentrated to dryness, the corresponding acid chloride being obtained, which is mixed with a concentrated ethereal ammonia solution. The resulting solution is concentrated, 5-n-octyl-7-methylsulfinylxanthone-2-carboxamide is obtained. ■

The lower alkylamides can be prepared in the same way by replacing the ammonia in the above process with " a monoalkylamine or dialkylamine. In this way, for example, the 5-n-octyl-7-methylsulfamoylxanthone-2-carboxamide is obtained,
N-methyl-5-n ~ octyl-7-propylsulphinylxanthone-2-carboxamide, N ^ -diethyl-Sn-octyl ^ -ethylsulphonylxanthone - ^ - carboxamide,

N-n-Propyl-5-n-octyl-7- (propylsulfinyl) -xanthone-2-carboxamide etc.

509829/0988

Example 15

To a mixture of 20 g procaine and 500 ml aqueous Methanol becomes 20 g of 5-n-octyl-7-methylsulfinylxanthone-2-carboxylic acid admitted. The resulting mixture is stirred for 16 hours at low temperature and then at ver * .concentrated under reduced pressure, whereby the procaine salt of 5-n-Octyl-7-ynethylsulfinylxanthone-2-carboxylic acid is obtained.

In the same way are the lysine, caffeine and arginine salts shown. Also, for example, the procaine, lysine, caffeine and arginine salts of other components of the invention 5,7-disubstituted xanthone-2-carboxylic acids are obtained e.g. the procaine salt of 5-n-octyl-7-ethylsulfonylxanthone-2-carboxylic acid,

caffeine as 5- (propylsulfinyl) -7-n-octyloxyxanthone-2-carboxylic acid,

the procaine salt of 5- (sec-butylsulfinyl) -7-n-octyloxyxanthone-2-carboxylic acid. ·

Example 16

This example illustrates the method of manufacturing pharmaceutical Preparations containing the present compounds. ·

0.44 g of sodium chloride are dissolved in 80 ml of a sodium hydrogen phosphate solution (9/47 g per liter of water) dissolved. then 20 ml of a sodium dihydrogen phosphate solution (8.00 g per liter of water) added. The resulting solution of pH 7i38 is sterilized in an autoclave. This carrier will then with solid, dry 5-n-octyloxy-7-methylsulfinylxanthone-2-carboxylic acid combined to obtain a preparation which is suitable for intravenous injection and

5098 2.9 / 0988

the 2.5 mg S-n-octyloxy-T-methylsulfinylxanthone - ^ - carboxylic acid per ml contains.

• Example 17

The compounds mentioned below are in rats by means of the method of passive cutaneous anaphylaxis (PCA) with homocytotropic reaginine antibodies, as essentially by I. Mota _; Immunology 7, 6-81 (1964). This method determines the inhibitory effect of a compound on the release of spasmogenic substances through the antigen-antibody reaction (allergic reaction). .

Normal female Sprague-Dawley rats weighing 1 ^ 0 to 16o g are passively sensitized on both sides by intradermal injection of rat anti-albumin reaginine serum (antibody). After 2k hours, each rat is challenged intravenously with 1 ml physiological saline solution containing 0.5% Evans blue, 1 mg egg albumin (antigen) and the compound to be tested. The inflammation caused by the antigen-antibody reaction is shown by the skin turning blue, which is detected 15 to 25 minutes after the irritation. The average diameter of the blue zone is measured (mm + _ SE) and used to calculate the inhibitory effect on the inflammatory response; this inhibitory effect is in % against the control group

expressed. . .

509829/0988

- i \ 6 -

Link PCA activity

. (Disodium cromoglycate = 1) finylxanthone-2-carboxylic acid - ^ - 20

Example l8

A dose of 100 mg / kg body weight of 5-n-octyloxy-7-methylsulfinylxanthone-2-carboxylic acid is administered intraperitoneally to guinea pigs administered. Comparison animals are left untreated. After the treatment, the treated and the comparison animals an aqueous spray of o, o5 / S histaraindiphosphate (calculated as base), which is released from a nebulizer until it has the ability to Lose uprightness. After exposure to the mist, the animals are observed for the severity of the reactions. The response ranges from slightly deeper breathing to deep breathing to pre-convulsive wheezing and ataxia to collapse. The one with 5-n-octyloxy-7-methylsulfinylxanthone-2-carboxylic acid treated porcupines have considerable resistance against irritation from the histamine aerosol, while collapse in the comparison animals during the exposure time entry. . ·

509829/0988

Protection against an aerosol caused by Histan?.: Lp. ~ Bronchial constriction is considered representative and translatable to the effectiveness on bronchi and lungs in humans considered. For example, patients suffering from respiratory diseases are sensitive to the severity of bronchial spasms and their change and. me «bare. Changes in respiratory function observed. Appropriate measurements include determining the amount of air exhaled and comparing the airflow Lung volume before and after treatment with the inventive Connections, for example by spirometric and / or pletismographic methods. The subjective relief dor symptoms after administration of the invention. Compounds shows up in less breathlessness, less wheezing and coughing and less. Sputum amounts.

509829/0988

Claims (1)

Claims ί ! ^ / compounds of the formula: COOH in which one R is an alkyl or alkoxy radical having 6 to 12 carbon atoms and the other R is the radical means, where η is the number 1 or 2 and R is a lower alkyl radical, and their pharmaceutically acceptable, non-toxic esters, amides and salts. 2) Compounds according to claim 1 with the formula: COOH wherein R is a lower alkylsulphynyl or lower alkylsulphonyl radical and R is an alkyl radical having 6 to 12 carbon atoms. 3) Compounds according to claim 1 with the formula: 509829/0988 ■ ', J » . Q COOH wherein R is a lower alkylsulphinyl or lower alkylsulphonyl radical and R is an alkyl radical having 6 to 12 carbon atoms. * 0 connection according to claim 3 »characterized by 2 ' ¹ I. shows that R is the methylsulfinyl radical and R is the n-octyl radical and the compound is 5-n-octyloxy-T-methylsulfinylxanthone-2-carboxylic acid is. 5) Connection according to claim 3> characterized by 2 · i | shows that R denotes the methylsulfinyl radical and R denotes the N-dodecyl radical and the compound denotes the 5 ™ n-dodecyloxy-7-methylsulfinylxanthone-2-carboxylic acid is. 6) "\ ferbindungen according to claim 1 with the formula: COOH wherein R is a lower alkylsulphinyl or lower alkylsulphonyl radical and R is an alkyl radical having 6 to 12 carbon atoms means. · "509829/0988 . "» ■ ■ ⁵⁰ - 7) connection according to claim 6, characterized P 'fl shows that R is the methylsulfinyl radical and R is the n-octyl radical and the compound denotes 5-methylsulfinyl-7-n-octyloxyxanthone-2-carboxylic acid is. - 8) Connection according to claim 6, characterized p C shows that R is the methylsulfinyl radical and R is the n-dode ~ Cyl radical and the compound denotes 5-methylsulfinyl-7 ~ is n-dodecyloxyxanthone-2-carboxylic acid. 9) sodium salts of the compounds according to claim 1, 10) A preparation for inhibiting the effects of allergic reactions comprising an effective amount of a compound the formula: COOII wherein one R is an alkyl or alkoxy radical having 6 to 12 carbon atoms and the other R the rest means, where η is the number 1 or 2 and R is a lower one
Represents alkyl radical, or a pharmaceutically acceptable, non-toxic ester, amido or salt thereof in combination with a pharmaceutically acceptable, non-toxic 509829/0988 Carrier. 11) Compounds of the formula: wherein one R is the hydroxy group and the other R is Remainder 0 0 II Il. R-S-, R-S- or R-S-, 71 where R is a lower alkyl radical and R is hydrogen or a lower alkyl radical. 12) compound according to claim 11, characterized in that that R denotes the methyl radical. 13) 5-hydroxy-7-methylthioxanthone-2-carboxylic acid according to claim 12; "· I ¹ I) 5-methylthio-7-hydroxyxanthone-2-carboxylic acid according to claim 12. -. 15) 5-methylsulfinyl-7-hydroxyxanthone-2-carboxylic acid according to claim 12. 16) 5-methylsulfonyl-7-hydroxyxanthone-2-carboxylic acid according to claim 12. 17) ^ -Hydroxy ^ -nethylsulfinylxanthone ^ -carboxylic acid according to claim 12. 18) 5-Hydroxy-7-methylsulfonylxanthone-2-carbon i,
acid according to claim 12.. 509829/0988 '' 19) Process for the preparation of a compound of the formula: ·. COOH wherein one R is an alkyl or alkoxy radical having 6 to 12 carbon atoms and the other R the rest R. ■ - where η is the number 1 or 2 and R is a lower alkyl radical, and the pharmaceutically acceptable one non-toxic esters, amides and salts thereof, characterized in that one 1) a 5 (7) -alkyl- or 5 (7) -alkoxy-7 (5) -alkylthioxanthone-2-carboxylic acid or a lower alkyl ester thereof is oxidized with a peracid or hydrogen peroxide and then hydrolyzed, if desired, to form the corresponding 5 (7) -alkyl or 5 (7) -alkoxy-7 (5) -alkylsulfinylxanthone-2-carboxylic acid or a lower alkyl ester of the same or the corresponding 5 (7) -alkylsulfonyl-5 '(7) -alkyl- or alkoxy-xanthone-2-carboxylic acid or a lower one Alkyl esters thereof and 2) desired fnllc. the Yer- ORiGIMAL 509829/0988 ' \ -53- bond to their pharmaceutically acceptable, non-toxic esters, amides and salts. 20) Process for the preparation of a compound of the formula: '· - wherein one R is an alkoxy radical having 1 to 12 carbon atoms and the other R is the radical -S (O) _n
R. means, where η is the number 1 or 2 and R is a lower alkyl radical, and the pharmaceutically acceptable, non-toxic esters, amides and salts thereof, characterized in that one 1) a 5 (7) -hydroxy-7 (5) -lower alkylthio-xanthone-2-carboxylic acid or a lower alkyl radical thereof is alkylated by means of an alkyl halide having 1 to 12 carbon atoms, then, if desired, hydrolyzed the ester obtained or esterified the carboxylic acid obtained and the The compound is then oxidized with a peracid or hydrogen peroxide to form the corresponding 5 (7) -alkoxy-7 (5) -lower alkylsulfinylxanthone-2-carboxylic acid or a lower one . 509829/0988 · ' • - 51 - Alkyl esters of the same or of the corresponding 5 (7) -alkoxy-7 (5) -lower alkylsulfonylxanthone-2-carboxylic acid or a lower alkyl ester thereof, or 2) a 5 (7) hydroxy-7 (5) lower alkylthioxanthone-2-carboxylic acid or a lower alkyl ester thereof is oxidized with a peracid or hydrogen peroxide, then if desired hydrolyzed the ester obtained or esterified the carboxylic acid obtained and then the compound by means of a Alkyl halide having 1 to 12 carbon atoms. with formation of the corresponding 5 (7) -alkoxy-7 (5) -lower alkylsulfinylxanthone-2-carboxylic acid or a lower alkyl ester thereof or the corresponding 5 (7) -alkoxy-7 (5) -lower alkylsulfonylxanthone-2-carboxylic acid or a lower alkyl ester thereof, and 3) if desired, those in the first or second stage obtained ester hydrolyzed to the corresponding free 2-carboxylic acid, and ή) if desired, the carboxylic acid obtained in stage 1, 2 or 3 converted to their pharmaceutically acceptable, non-toxic esters, amides and salts. 21) Method according to claim 20, characterized in that that the starting product used in stage 1 or 2 by cleavage of the alkoxy group of a 5 (7) -alkoxy-7 (5) -lower alkylthioxanthone-2-carboxylic acid or a lower alkyl ester of the same by means of hydrogen bromide 509829 / Ö988. •, · -55- or hydriodic acid and any esterification. 22) Method according to claim 2I _5, characterized in that the alkoxy group is a methoxy group. 50a829 / 0988