MXPA01006230A

MXPA01006230A - Sulphonyloxazolamines as therapeutic active ingredients

Info

Publication number: MXPA01006230A
Application number: MXPA/A/2001/006230A
Authority: MX
Inventors: Bottcher Henning; Bartoszyk Gerd; Greiner Hartmut; Barnickel Gerhard; Cezanne Bertram
Original assignee: Merck Patent Gmbh
Priority date: 1998-12-18
Filing date: 2001-06-18
Publication date: 2002-05-09

Abstract

The present invention relates to sulphonyloxazolamines of general formula (I), wherein R1, R2 represent independently from each other H, A, -(CH2)n-Ar or alkenyl with 2-6 C atoms, R1 and R2 together also represent a mononuclear saturated heterocycle with 1-2 N, O and/or S atoms, Z is H, A, CF3, NO2, Hal, OH, OA, NH2, NHA or NA2, A represents alkyl with 1-6 C atoms, Ar is Z-monosubstituted or Z-disubstituted phenyl, Hal is F, Cl, Br or I, n is 1 or 2 or the physiologically acceptable salts or solvates thereof. Said sulphonyloxazolamines are used as therapeutic active ingredients. The invention also relates to the use of sulphonyloxazolamines as therapeutic active ingredients and/or to the production of pharmaceutical preparations to combat diseases of the central nervous system. The invention further relates to a pharmaceutical preparation and the production thereof.

Description

SULFONYLOXAZOLAMINES AS THERAPEUTIC ACTIVE INGREDIENTS DESCRIPTION OF THE INVENTION The invention relates to the sulfonyloxazolamines of the general formula I below: where R1, R2 Each one independent of the other is H, A, - (Chb Ar or alkenyl, having 2 to 6 carbon atoms R1 and R2 Together they also form a saturated mononuclear heterocycle, with 1 or 2 N, O atoms and / o S Is H, A, CF3, NO2, Hal, OH, OA, NH3, NHA or NA2 It is alkyl with 1 to 6 carbon atoms Ite: 12B865 Ar Is phenyl, which is mono or dis-substituted with Z Hal Is F, CL, Br or I It is 1 or 2 or its physiologically acceptable salts or solvates as therapeutic active compounds.

The invention, furthermore, relates to the use of the sulfonyloxazolamines of the general formula I as active therapeutic compounds.

The invention also relates to the use of the sulfonyloxazolamines of the general formula I for pharmaceutical preparations aimed at controlling disorders of the central nervous system.

Some of the compounds of the general formula I are known from several past publications. Therefore, the preparation of the compounds of the formula I is described in V.A. Chernovyl et al., Uhr. Khim. Zh. (Russ. Ed.) 1991, 57 (4), 415-418 or V.A. Chernovyl et al., Zh. Org. Khim. 1988, 24 (2), 453-4 corresponding to a V.A. Chernovyl et al., J. Org. Che. USSR (English translation), 1988, 24, 401. Prior to this no other detailed publications are available regarding the pharmacological efficacy of the compounds of formula I.

The invention is based on the purpose of finding new beneficial properties of the sulfonyloxazolamines, in particular those which confirm that the compounds are active therapeutic compounds and / or can lead to the use of the sulfonyloxazolamines as therapeutic active compounds and / or to the production of pharmaceutical preparations. .

It has been found that the compounds of the formula I and their respective salts surprisingly have a selective affinity for the 5-HT 6 receptors, together with a good tolerability. They exhibit 5HT6-antagonists or agonistic 5-HT6 actions.

The 5-HT6 receptors form a subfamily of 5-HT receptors. The neurotransmitter 5-hydroxytryptamine (5-HT), also known as serotonin, is an important neurotransmitter regulator of the brain, whose actions are assisted by a family of receptors that, as far as is known, contains 13 receptors coupled with protein and a channel ionic.

The highest density of 5-HT6 serotonin receptors in the brain is found in the olfactory tubercle, the auditory nucleus, the striatum, the dentate fascia and the CA1-3 regions of the hippocampus. These regions are involved, to some extent, with psychiatric disorders, such as, for example, schizophrenia or depression. Furthermore, it is known from animal experiments that administration of anti-sense oligonucleotides 5-HT6 results in a behavioral syndrome corresponding to that of dopamine agonists. In addition, the hyperactivity of the dopaminergic neurotransmitter system of schizophrenia (the hypothesis of dopamine schizophrenia is pathophysiologically confirmed, however, dysfunctions of the dopamine system have been demonstrated in several forms of depression. They are used in clinical practice for the treatment of these psychiatric disorders, a large number of which bind with the 5-HT6 receptor, and here, in particular, the atypical neuroleptics (for example, clozapine) and the tricyclic antidepressants (ex. ., amitriptyline).

In addition, in investigations of animal experiments it was found that 5-HT6 receptors in the brain control cholinergic neurotransmissions. Cholinergic drugs are used to treat memory disorders, such as Alzheimer's disease.

For these reasons, it can be concluded that there is a participation of the 5-HT6 receptor in psychiatric or neurological dysfunctions, such as schizophrenia, depression and Alzheimer's disease.

The compounds of the formula I and their physiologically acceptable salts are therefore suitable as therapeutic active compounds for treating disorders of the central nervous system. The compounds of the formula I and their physiologically acceptable salts are suitable as therapeutic active compounds for the treatment of psychosis, schizophrenia, manic depression (BL Roth, et al., J. Pharmacol. Exp. Ther. 1994, 268, 1403- 1410), depression (DR Silbey et.al., Mol.Pharmacol., 1993, 43, 320-327), neurological disorders (A. Bourson et al., J. Pharmacol. Exp. Ther 1995, 274, 173-180). , memory disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease (AJ Sleight et al., Neurotransmissions, 1995, 11, 1-5), bulimia, anorexia nervosa or other eating disorders, compulsive acts or premenstrual syndrome.

The invention relates to the compounds of the formula I or their physiologically acceptable salts or solvates as therapeutic active compounds.

The invention, furthermore, relates to the use of the compounds of the formula I or their physiologically acceptable salts or solvates as therapeutic active compounds, for treating disorders of the central nervous system.

The solvates of the compounds of the formula I are understood as adducts of solvent molecules inert to the compounds of the formula I which are formed due to their mutual attractive force. Solvates are, for example, mono or dihydrates or alcoholates.

For all the radicals that appear more than once, such as Z, it is true that their meanings are independent of each other.

Up and down, the radicals and parameters R1, R2r, Z and n have the meanings indicated in forms I to VI, if they are not expressly stated otherwise.

In the above formulas, A is alkyl, linear or branched, and has from 1 to 6, preferably 1, 2.3 or 4 carbon atoms. A is preferably methyl, in addition ethyl, propyl, butyl, isobutyl, sec-butyl or tert-butyl, in addition also pentyl, 1-, 2- or 3-methylbutyl, 1, 1-, 1, 2- or 2,2-dimethylpropyl. , 1-ethylpropyl or hexyl. Methyl is particularly preferred. The alkenyl is preferably allyl, 2- or 3-butenyl, isobutenyl, sec-butenyl, further preferably it is 4-pentyl, isopentenyl or 5-hexenyl. Allyl is particularly preferred for alkenyl.

Ar is preferably phenyl, which is mono or disubstituted with Z, wherein Z can be H, A, CF3, NO2, Hal, OH, OA, NH2, NHA or NA2.

Therefore, Ar is preferably phenyl, o-, m- or p-methylphenyl, o-, m- or p-ethylphenyl, o- or p-propylphenyl, o-, m- or p-isopropylphenyl, or-, m- or p-tert-butylphenyl, o-, m- or p-aminophenyl, o-, m- or pN, N-dimethylaminophenyl, o-, m- or p-nitrophenyl, o-, m-, or p- hydroxyphenyl, o-, m-, or p-methoxyphenyl, o-, m- or p-toxyphenyl, o-, m-, p-trifluoromethylphenyl, o-, m- or p-fluorophenyl, o-, m- or p chlorophenyl, o-, m- or p-bromophenyl, furthermore preferably 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethylphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dihydroxyphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-Ó 3,5 -difluorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-03,5- dichlorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-0 3,5-dibromophenyl, 2,3-, 2,4-, 2 , 5-, 2.6-, 3.4-O 3,5-dimethoxyphenyl.

Phenyl, o-, or p-methylphenyl, o- or p-chlorophenyl, p-bromophenyl, p-methoxyphenyl or 2,4-dichlorophenyl are particularly preferred for Ar. In - (CH2) n -Ar, Ar has one of the preferred meanings indicated above, wherein n can be 1 or 2. Particularly preferred is benzyl for - (CH2) n -Ar, Hal is preferably fluorine, chlorine or bromine.

Z is H, A, CF3, NO2, Hal, OH, OA, NH2, NHA or NA2, wherein A and Hal have one of the preferred meanings indicated above. H, methyl, chloro, bromo or methoxy are particularly preferred for Z. n is preferably 1 or 2, particularly preferably 1.

R1 and R2 together are preferably tetrahydro-2- or -3-furyl, 1,3-dioxolan-4-yl, tetrahydro-2- or -3-thienyl, 1-, 2- or 3-pyrrolidinyl, tetrahydro-1- , -2- or -4-imidazolyl, tetrahydro-1-, -3- or -4-pyrazolyl, 1-, 2-, 3-, or 4-piperidinyl, 1-, 2-, 3-, or 4- perhydroazepinyl, 1-, 2-, 3-, or 4-morpholinyl, tetrahydro-2-, -3- or 4-pyranyl, 1,4-dioxanil, 1,3-dioxan-2-, -4- or -5 -yl, hexahydro-1-, -3- or -4- pyridazinyl, hexahydro-1-, -2-, -4- or -5-pyrimidinyl or 1-, 2- 3-piperazinyl. The 1-piperidinyl or 4-morpholinyl is particularly preferred for the resonances R1 and R2 together.

For the subject of the invention of the therapeutic active compounds of the formula I or their physiologically acceptable salts or solvates, for the use of the compounds of the formula I or their physiologically acceptable salts or solvates or for the production of a pharmaceutical preparation for the treatment of central nervous system disorders, in particular those compounds of the formula I in which at least one of the radicals mentioned has one of the preferred or preferred meanings in a particular manner indicated above are preferred. Some groups of preferred compounds can be expressed by the following sub-forms of the al, which correspond to the formula I and in which the radicals not described in great detail have the meaning indicated in the formula I, but in which R 1 and R2 in each case independently of one another are H, A, - (CH2) n-Ar or alkenyl, having from 2 to 6 carbon atoms; in Ib R1 and R2 in the formula I together are 1-piperidinyl.

(CH2) n-OA In it, R1 and R in formula I, together, are 4-morpholinyl; you The following compounds of formulas la, Ib and le are those that are particularly preferred to be used according to Claim 1: dimethyl- [2-phenyl-4- (toluene-4-sulfonyl) oxaxol-5-yl] amine; [2- (2,4-dichlorophenyl) -4- (toluene-4-sulfonyl) oxazol-5-yl] dimethylamine; benzyl- [2- (2,4-dichloropheni) -4- (toluene-4-sulfonyl) -oxazol-5-yl] -amine; methyl- [4- (toluene-4-sulphonyl) -2-p-tolyloxazol-5-yl] amine; benzyl [4- (4-chlorobenzenesulfonyl) -2- (2,4-disorophenyl) oxazol-5-yl] amine; (4-benzenesulfonyl-2-r? -tolyloxazol-5-yl) benzylamine; [4- (4-chlorobenzenesulfonyl) -2-p-tolyloxazol-5-yl] -dimethylamine; (4-benzenesulfonyl-2-o-tolyloxazol-5-yl) -methylamines; benzyl- [4- (4-chlorobenzenesulfonyl) -2- (2-chlorophenyl) -oxazol-5-yl] amine; [4-benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] -benzylamine; [4-benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] dimethylamine; [4-benzenesulfonyl-2- (2-chlorophenyl) oxazol-5-yl] -dimethylamine; 1- [2- (2,4-dichlorophenyl) -4- (toluene-4-xulfonyl) -oxazol-5-yl] piperidine; 1 - [4-Benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] piperidine; 1 - [4-benzenesulfonyl-2- (2-chlorophenyl) oxazol-5-yl] piperidine; 4- [4- (toluene-4-sulfonyl) -2-p-tolyloxazol-5-yl] morpholine; 4- [4- (4-chlorobenzenesulfonyl) -2-p-tolyloxazol-5-yl] morpholine; 4- [4- (4-chlorobenzenesulfonyl) -2-phenyloxazol-5-yl] morpholine; 4- [4- (4-benzenesulfonyl) -2- (4-bromophenyl) oxazol-5-yl] morpholine; 4- [4- (4-benzenesulfonyl) -2-m-tolyloxazol-5-yl] morpholine; 4- [4- (4-benzenesulfonyl) -2- (4-methoxyphenyl) oxazol-5-yl] morpholine; 4- [4- (4-benzenesulfonyl) -2-phenyloxazol-5-yl] morpholine; allyl- (4-benzenesulfonyl-2-phenyloxazol-5-yl) amine; 4- (4-Benzenesulfonyl-2- (2-chlorophenyl) oxazol-5-yl] morpholine; (4-benzenesulfonyl-2-phenyloxazol-5-yl) dimethylamine; (4-benzenesulfonyl-2- / T7-tolyloxazol-5-yl) dimethylamine; benzyl- [2-phenyl-4- (toluene-4-sulfonyl) oxazol-5-yl] amine and benzyl- [4- (toluene-4-sulfonyl) -2- # 77-tolyloxazol-5-yl] amine.

In relation to formula la, the following known compounds are preferred for use as therapeutic active compounds: dimethyl- [2-phenyl-4- (toluene-4-sulfonyl) oxazol-5-y.] amine; [2- (2,4-dichlorophenyl) -4- (toluene-4-sulfonyl) oxazol-5-yl] dimethylamine; benzyl- [2- (2,4-dichlorophenyl) -4- (toluene-4-sulfonyl) -oxazol-5-yl] amine; methyl- [4- (toluene-4-sulfonyl) -2-p-tolyloxazol-5-yl] amine; benzyl- [4- (4-chlorobenzenesulfonyl) -2- (2,4-dichlorophenii) oxazol-5-yl] amine; (4-benzenesulfonyl-2- / t? -tolyloxazol-5-yl) benzylamine; [4- (4-chlorobenzenesulfonyl) -2-p-tolyloxazol-5-yl] dimethylamine; (4-benzenesulfonyl-2-o-tolyloxazol-5-yl) methylamine; benzyl- [4- (4-chlorobenzenesulfonyl) -2- (2-chlorophenyl) -oxazol-5-yl] amine; [4-benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] benzylamine; allyl- (4-benzenesulfonyl-2-phenyloxazol-5-yl) amine; (4-benzenesulfonyl-2-phenyloxazol-5-yl) dimethylamine; (4-benzenesulfonyl-2-m-tolyloxazol-5-yl) dimethylamine; benzyl- [2-phenyl-4- (toluene-4-sulfonyl) oxazol-5-yl] amine; benzyl- [4- (toluene-4-sulfonyl) -2-77-tolol-oxazol-5-yl] amino; [4-benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] dimethylamine and [4-benzenesulfonyl-2- (2-chlorophenyl) oxazol-5-yl] dimethylamine.

In relation to formula Ib, the following known compounds are preferred for use as therapeutic active compounds. 1-2- (2,4-dichlorophenyl) -4- (toluene-4-sulfonyl) oxazol-5-yl] piperidine; 1- [4-benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] piperidine and 1- [4-benzenesulfonyl-2- (2-chlorophenyl) oxazol-5-yl] piperidine.

In relation to the formula, the following known compounds with which they are preferred to be used as therapeutic active compounds: 4-r4- (toluene-4-sulfonyl) -2-p-tolyloxazol-5-yl] -morpholine; 4- [4- (4-chlorobenzenesulfonyl) -2-p-tolyloxazol-5-yl] -morpholine; 4- [4- (4-chlorobenzenesulfonyl) -2-phenyloxazol-5-yl] -morpholine; 4- [4- (4-benzenesulfonyl) -2- (4-bromophenyl) oxazol-5-yl] morpholine; 4- [4- (4-benzenesulfonyl) -2-t? -tolyloxazol-5-yl] -morpholine; 4- [4-benzenesulfonyl) -2- (2-chlorophenyl) oxazol-5-yl] -morpholine; 4- [4- (4-benzenesulfonyl) -2- (4-methoxyphenyl) oxazol-5-yl] -morpholine and 4- [4- (4-benzenesulfonyl) -2-phenyloxazol-5-yl] -morpholine; The invention also relates to the use of the following compounds, selected from the group. a) dimethyl- [2-phenyl-4- (toluene-4-sulfonyl) oxazol-5-yl] amine, b) [2, (2,4-dichlorophenyl) -4- (toluene-4-sulphonyl) oxazol-5-yl] dimethylamine, c) benzyl- [4- (4-chlorobenzenesulfonyl) -2- (2-chlorophenyl) oxazol-5-yl] amine, d) (4-benzenesulfonyl-2-o-tolyloxazol-5-yl) -methylamine e) benzyl- [2- (2,4-dichlorophenyl) -4- (toluene-4-sulfonyl) oxazol-5-yl] amine, f) [4-Benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl-benzylamine g) [4-Benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] dimethylamine. or one of its physiologically acceptable salts or solvates as therapeutic active compounds against disorders of the central nervous system.

The compounds of formula I are generally commercially available or can be synthesized according to the following synthesis scheme (for this cf. et al., Ukr. Khim. Zh. (Russ. Ed.) 1991, 57 (4), 415-416 or V.A. Chervonyi et. At., J. Org. Chem. USSR (English translation) 1988, 24, 401.

Synthesis scheme: In the synthesis scheme shown above, the starting material of formula II was reacted with trichloroacetate to obtain compound III. The reaction with thionyl chloride and subsequently with the sodium sulfinate of the formula V generates an aryl vinyl sulfone of the formula VI, which is cycled to obtain sulfonyloxazolamines of the formula VII. In this relation, the substitutes Ar, Z, R1 and R2 of the formulas from II to VII have preferential or particularly preferential meanings as indicated above. The most appropriate reaction conditions of the aforementioned reactions of the synthesis scheme are known based on the references of V.A. Chervonyi et al., Ukr. Khim. Zh. (Russian Edition) 1991, 57 (4), 415-418 or V.A. Chervonyi et al., Org. Khim 1988, 24 (2), 453-4 which correspond to V.A. Chervonyi et al., J. Org. Chem U.R.S.S. (English translation) 1988, 24, 401 or standard works such as, for example, Houben-Weyl, Methods of Organic Chemistry. { Methoden der organischen Chemie), Georg- Thieme- Verlag, Stuttgart. In this case, the use can also be carried out of variants known per se but not mentioned in detail in the present document.

A base of the formula I can be converted into the associated acid addition salt using an acid, for example by reaction of equivalent amounts of the base and the acid in an inert solvent such as ethanol with subsequent evaporation. For this reaction, the most appropriate acids are particularly those which provide physiologically acceptable salts. Therefore, inorganic acids such as for example sulfuric acid, nitric acid, hydrohalic acids, such as hydrochloric acid or hydrobromic acid, phosphoric acids such as orthophosphoric acid, sulfamic acid and further the acids can be used. organic, in particular monobasic or polybasic aromatic or heterocyclic carboxylic acids and sulphonic or sulfuric acids, for example: formic acid, ascetic acid, propionic acid, pivalic acid, diethylesacetic acid, malonic acid, succinic acid, acid pimelic acid, fumaric acid, maleic acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinic acid, methane or ethanesulfonic acid, p-toluenesulfonic acid, mononaphthalene and disulfonic acids or acid sulfuric lauryl. Salts with physiologically unacceptable acids, for example picrates, can be used for the isolation and / or purification of the compounds of the formula I. The linking of the compounds of the formula I with the 5-HT6 receptors was determined as follows way: The substances to be tested were dissolved in DMSO at a concentration of 1 mM and diluted to the desired concentrations (0.1 nM to 10 μM) using a test buffer (20 mM HEPES, 0.1% ascorbic acid adjusted to a pH of 7.4 using NaOH). μl of the solution with the respective substance were incubated at 37 ° C for 1 hour with 80 μl of a solution of 3H-LSD (TRK-1041, Amersham Pharmacia, Freiburg, act spec.80-90 Ci / mMol, 1 nM in the batch) and 100 μl of a membrane suspension (5-HT6 receptors, RB-HS6, Biotrend, Colony, 25-30 μg of protein). The reaction mixture was filtered through GFB filters (Whatman) which had been pretreated with an aqueous solution of 0.1% polyethylenimine for 1 hour. The filters were washed 3 times with 3 ml of test buffer, the filters [according to the text] were transferred to small bottles and after the addition of Ultima Gold (Packard, Frankfurt), the radioactivity was determined in a scintillation counter liquid. The evaluation and determination IC50 was carried out by means of internal programs in RS1 (BBN Software Corporation).

The compounds of the formula I possess a selective affinity for the 5-HT6 receptors having an inhibition constant IC50 of less than 4 μmol / l. In addition, the invention relates to the use of the compounds of the general formula I for the production of a pharmaceutical preparation for controlling disorders of the central nervous system.

In addition, the invention relates to the use of the compounds of the general formula I for the production of a pharmaceutical preparation for the treatment of psychosis, schizophrenia, manic depression, depression, neurological disorders, memory disorders, Parkinson's disease, sclerosis. amyotrophic lateral, Alzheimer's disease, Huntington's disease, bulimia, anorexia nervosa and other eating disorders, compulsive acts or premenstrual syndrome.

In addition, the invention relates to pharmaceutical preparations for the control of central nervous system disorders comprising at least one compound of formula I or one of its physiologically acceptable salts or solvates. These preparations can be used as pharmaceuticals in both human and veterinary medicine, the possible vehicles are organic or inorganic substances suitable for enteral (eg oral) or parenteral administration or topical application and do not react with the new compounds, for example water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glycerol triacetate, gelatin carbohydrates such as lactose and starch, magnesium stearate and talcum jelly. Petroleum. Tablets, pills, coated tablets, capsules, powders, granules, syrups, juices or drops, in particular, are used for oral administration, suppositories are used for rectal administration, solutions; preferably the oily or aqueous solutions, additionally, the suspensions, emulsions or implants are used for parenteral administration and the ointments, creams or powders are used for topical application. The new compounds can also be lyophilized and the lyophilizates obtained are used, for example, for the production of injectable preparations. The stated preparations can be sterilized and / or contain excipients such as lubricants, preservatives, stabilizers and / or wetting agents, emulsifiers, salts for influencing the osmotic pressure, buffer substances, colorants, flavors and / or other active compounds such as for example one or more vitamins The invention also relates to a process for the production of these pharmaceutical preparations, which is characterized in that a compound of the formula or one of its physiologically acceptable salts or solvates is converted into a convenient dose together, at least, with a solid, liquid or semi-liquid vehicle or in any case an excipient and, if appropriate, in combination with one or more active compounds. The compounds of the formula I and their physiologically acceptable salts or solvates can be used for the control of central nervous system disorders. The substances according to the invention are administered here as a rule in doses which are preferably between 1 and 500 mg, and particularly between 5 and 100 mg per unit dose. The daily dose is preferably between 0.02 and 10 mg / kg of body weight approximately. However, the specific dose for each patient depends on several factors, for example, on the efficacy of the specific compound used, on age, body weight, general health, sex, diet, time and route of treatment. administration, in the frequency of excretion, in the pharmaceutical combination and in the severity of the particular disorder for which the therapy is being applied. Oral administration is preferred. The following examples relate to pharmaceutical preparations: Example A: Injection ampoules A solution of 100 g of an active compound of the formula I and 5 g of disodium hydrogen phosphate is adjusted to a pH of 6.5 in 3 I of double distilled water using 2N hydrochloric acid, sterile filtrate and emptied in ampoules of injection, lyophilized in sterile conditions and sealed aseptically. Each injection vial contains 5 mg of active compound.

Example B: Suppositories A mixture of 20 g of an active compound of the formula I is used with 100 g of soy lecithin and 1400 g of cocoa butter, emptied into molds and allowed to cool. Each suppository contains 20 mg of active compound. Example C: Solution A solution of 1 g of an active compound of the formula I, 9.38 g of NaH 2 PO 4"2 H 2 O, 28.48 g of Na 2 HPO 4" 12 H 2 O and 0.1 g of Benzalkonium Chloride in 940 ml of double distilled water is prepared. It is adjusted to a pH of 6.8, made up to 1 I and sterilized by irradiation. This solution can be used as ophthalmic drops. Example D: Ointment 500 mg of an active compound of the formula I are mixed with 99.5 g of petroleum jelly under aseptic conditions. Example E: Tablets A mixture of 1 kg of active compound of the formula I, 4 kg of lactose, 1.2 kg of potato starch. 0.2 g of talc and 0.1 kg of magnesium stearate are compressed in a customary manner such that each tablet contains 10 mg of the active compound.

Example F: Coated Tablets Analogously to Example E, the tablets are pressed and then coated in the usual manner with a layer of sucrose, potato starch, talc, tragacanth and dye.

Example G: Capsules 2 kg of active compound of the formula I are emptied into hard gelatine capsules in the customary manner such that each capsule contains 20 mg of the active compound. Example H: Ampoules A solution of 1 kg of the active compound of the formula I in 60 ml of double distilled water is sterile filtered, emptied into ampoules, lyophilized under sterile conditions and sealed aseptically. Each vial contains 10 mg of active compound. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention

Claims

Claims Having described the invention as above, the content of the following claims is claimed as property:

1. Compounds of the formula I characterized in that R \ R2 each independently of the other is H, A, - (CH2) p-Ar or alkenyl, having from 2 to 6 carbon atoms R1 and R2 together, furthermore, form a saturated mononuclear heterocycle, with 1 or 2 atoms of N-, O and / or S is H, A, CF3) NO2, Hal, OH, OA, NH3, NHA or NA2 A is alkyl with 1 to 6 carbon atoms Ar is phenyl, which is mono or di -substituted with Z Hal is F, CL, Br or I n is 1 or 2 or its physiologically acceptable salts or solvates as active therapeutic compounds.

2. Use of the compounds of the formula I as therapeutic active compounds.

3. The use according to claim 2, characterized in that the compounds of the formula | General or their physiologically acceptable salts or solvates are used as therapeutic active compounds for treating disorders of the central nervous system.

4. The use according to Claims 2 and 3, characterized in that the compounds a) dimethyl- [2-phenyl-4- (toluene-4-sulfonyl) oxazol-5-yl] amine, b) [2- (2,4-dichlorophenyl) -4- (toluene-4-sulfonyl) -oxazol-5-yl] dimethylamine, c) benzyl- [4 - (- chlorobenzenesulfonyl) -2- (2-chlorophenyl) oxazol-5-yl] amine, d) (4-benzenesulfonyl-2-o-tolyloxazol-5-yl) -methylamine e) benzyl- [2- (2,4-dichlorophenyl) -4- (toluene-4-sulfonyl) oxazol-5-yl) amine, f) [4-benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] benzylamine, g) [4-Benzenesulfonyl-2- (2,4-dichlorophenyl) oxazol-5-yl] dimethylamine or one of its physiologically acceptable salts or solvates are used as therapeutic active compounds for treating disorders of the central nervous system.

5. Use of the compounds of the general formula I for the production of a pharmaceutical preparation for the control of disorders of the central nervous system.

6. Use of the compounds of the general formula I according to claim 5 for the production of a pharmaceutical preparation for the treatment of psychosis, schizophrenia, manic depression, depression, neurological disorders, memory disorders, Parkinson's disease, lateral sclerosis amyotrophic, Alzheimer's disease, Huntington's disease, bulimia, anorexia, nervous disorders or other eating disorders, compulsive acts or premenstrual syndrome.

7. Pharmaceutical preparation for the control of disorders of the central nervous system, characterized in that it comprises at least one compound of the formula I or one of its physiologically acceptable salts or solvates.

8. Process for the production of pharmaceutical preparations, according to claim 7, characterized in that one of the compounds of the formula I and / or one of physiologically acceptable salts or solvates is brought to a suitable dose, together with at least a solid, liquid or semi-liquid vehicle or excipient and, if appropriate, in combination with one or more of the active compounds.