MXPA01007281A - Polycyclic 2-amino-thiazole systems, method for the production thereof and medicament containing said compounds - Google Patents

Abstract

The invention relates to polycyclic 2-amino-thiazole systems, their physiologically acceptable salts and physiologically functional derivatives. The invention describes polycyclic 2-amino-thiazole systems of formula (I), wherein the radicals have the cited meaning, their physiologically acceptable salts and a method for the production thereof. Said compounds are suitable, for example, as anoretics.

Description

POLYCYCLIC SYSTEMS 2-AMINO-TIAZOL, METHOD FOR THE PRODUCTION OF THESE AND MEDICINE THAT CONTAINS THESE COMPOUNDS The polycyclic 2-aminothiazole systems, the processes for their preparation and pharmaceutical compounds containing these compounds. The invention relates to polycyclic 2-aminothiazole systems and their physiologically tolerated salts and derivatives with physiological functionality. The 2-aminothiazole systems are described as anti-inflammatory substances in R. Gupta et al., Indian J. Pharm. Sci. 1991, 53, 245-248. The invention was based on the objective of providing compounds that show an anorectic effect that may be useful in treatments. The invention, therefore, relates to the compounds of the formula I: is a direct link, CH2, CH2-CH2 X is CH2, 0 R1 is CF3, CN, COOH, COO-alkyl (of C? -C6), CONH2, CONH (C? -C6 alkyl), CON [(C? -C6 alkyl)] 2, Ci-C? Alkyl, C2-Cd alkenyl, C2-C2 alkynyl, C-Ci-O-alkyl, where one or more of one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are substituted by fluorine or a hydrogen is substituted by OH, OC (0) CH3, OC (0) H, 0-CH2-Ph, NH2, NH-C0-CH3 or N (C00CH2Ph) 2; S02-NH2, S02NH-alkyl (of C? -C6), S02N [alkyl (of C-C6)] 2, S-alkyl (of C? -C6), S- (CH2) n-phenyl, S0-alkyl (of C? -C6), SO- (CH2) n-phenyl, S02-alkyl (of C? -C6), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to two times by F, Cl, Br, OH, CF3, N02, CN, 0CF3, 0- (Ci-Cß) alkyl, Ci-Ce alkyl, NH2; NH 2, NH-C 1 -C 6 alkyl, N (C 1 -C 6 alkyl) 2, C 1 -C 7 NH-acyl, phenyl, biphenylyl, 0- (CH 2) n -phenyl, where n can be 0- 6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl, it being possible for the phenyl, biphenylyl, naphthyl, pyridyl, furanyl and thienyl rings each one is substituted up to three times by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (of d-Ce), Cx-Ce alkyl, NH2, NH-Cx-C6 alkyl , N (C? -C6 alkyl) 2, SO2-CH3-CO0H, COO-C? -C6 alkyl, CONH2; 1,2,3-triazol-5-yl, it being possible for the triazole ring to be substituted at the 1, 2 or 3 position by methyl or benzyl; tetrazol-5-yl, it being possible for the tetrazole ring to be substituted in the 1 or 2 position by methyl or benzyl R1 'is H, CF3, CN, COOH, COO-C6-C6 alkyl / CONH2, CONH-C6-C6 alkyl, CON [C6-C6 alkyl], C6-C6 alkyl, alkenyl of C2-Ce, C2-C6 alkynyl, O-Ci-Cß alkyl, where one or more of one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are replaced by fluorine, or a hydrogen is replaced by OH, OC (0) CH3, OC (0) H, 0-CH2-Ph, NH2, NH-C0-CH3 or N (COOCH2Ph) 2; S02-NH2, S02NH-alkyl (from C? -C6), S02N [alkyl (from Ci-C6)] 2, S-alkyl (from C? -C6), S- (CH2) n-phenyl, S0-alkyl (of C? -C6), SO- (CH2) n-phenyl, S02-alkyl (of Ci-Cß), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to two times by F, Cl, Br, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2; NH2, NH-C-C6 alkyl / N (C6-C6 alkyl) 2, C-C7 NH-acyl, phenyl, biphenylyl, O- (CH2) n-phenyl, where n can be 0- 6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl, it being possible for the phenyl, biphenylyl, naphthyl, pyridyl, furanyl and thienyl rings each one is substituted up to three times by F, Cl, Br, I, OH, CF3, N02, CN, 0CF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH-C-alkyl C6, N (C? -C6 alkyl) 2, S02-CH3-C00H, COO-C? -C6 alkyl, C0NH2; 1,2,3-triazol-5-yl, it being possible for the triazole ring to be substituted at the 1, 2 or 3 position by methyl or benzyl; tetrazol-5-yl, it being possible for the tetrazole ring to be substituted in the 1 or 2 position by methyl or benzyl R2 is NH2, NHR3, NR4R5 R3 is C6-C6 alkyl, CN, CH = NH, C (= S) NH2, C (= NH) -NH-phenyl, it being possible for the phenyl ring to be substituted up to two times by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), alkyl of C? -C6, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO-C6-C6 alkyl, C0NH2; phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted up to three times by F, Cl, Br, I, OH, N02, CN, OCF3, O-alkyl (of C2-C6), C2-Cß alkyl, NH2, NH-C-C6 alkyl, N (C6-C6 alkyl) 2 / S02-CH3-COOH, C0-C6 COO-alkyl, CONH2; biphenylyl, 1- or 2-naphthyl, 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl, 5-tetrazolyl, it being possible for the biphenylyl, naphthyl, pyridyl, furanyl or thienyl rings each to be substituted until twice by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH-C? ~ C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO-C? -C6 alkyl, CONH2; CH2-phenyl, CH2-2-pyridyl or CH2-4-pyridyl, it being possible for the phenyl or pyridyl ring to be substituted once or twice by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O -alkyl (from C? -C6), C? -C6 alkyl, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) 2, SO2-CH3-COOH, COO-C-alkyl ? -C6, CONH2 R4 is C1-C6 alkyl, C3-C6 cycloalkyl, alkenyl? of C2-Ce, C3-C6 alkynyl, phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted once or twice by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O- alkyl (from C? -C6), C? -C6 alkyl, NH2, NH- C? -C6 alkyl, N (C? -C6 alkyl) 2 / S02-CH3-C00H, COO-C1-6 alkyl C ^ C0NH2 R5 is Ci-Cß alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted once or twice by F, Cl, Br , I, OH, CF3, N02, CN, OCF3 / O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH- C? -C6 alkyl, N (C? -C6 alkyl) ) 2, S02-CH3-COOH, COO-C6-C6 alkyl, CONH2; or R4 and R5 together form one of the groups CH2-CH2-CH2-CH2-CH2, CH2-CH2-N (CH3) CH2-CH2, CH2-CH2- N (CH2-phenyl) CH2-CH2, CH2-CH2-0 -CH2-CH2, CH2-CH2-CH2-CH2 and their physiologically tolerated salts and derivatives with physiological functionality.

Preference is given to compounds of formula I in which one or more radical (s) has the following meanings: And a direct link, CH2, CH2-CH2 X CH2, 0 Rl CF3, CN, COOH, COO-alkyl (from C? -C6), C0NH2, CONH (C? -C6 alkyl), CON [(C? -C6 alkyl)] 2, Ci-Ce alkyl, alkenyl of C2-Cd, C2-C6 alkynyl, O-C6-C6 alkyl, where one or more of one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are substituted by fluorine or a hydrogen is substituted by OH, OC (0) CH3, 0C (0) H, 0-CH2-Ph, NH2, NH-CO-CH3 or N (COOCH2Ph) 2; S02-NH2, S02NH-alkyl (of CL-C6), S02N [alkyl (of C? ~ C6)] 2, S-alkyl (of C? ~ C6), S- (CH2) nfyl, S0- alkyl ( of C? -C6), SO- (CH2) nfilo, S02-alkyl (of C? ~ Ce), S02- (CH2) n ~ f-enyl, where n can be 0-6 and the phenyl radical can be substituted up to two times by F, Cl, Br, OH, CF3, N02, CN, OCF3, O- (Ci-Cß) alkyl, Ci-Cß alkyl, NH 2; NH2, NH-C-C6 alkyl, N (C6-C6 alkyl) 2, C-C7-NH-acyl, phenyl, O-phenyl, it being possible for the phenyl ring to be substituted up to three times by F , Cl, Br, I, OH, CF3, N02, CN, OCF3, O- (C? -C6) alkyl, C? -C6 alkyl, NH2, NH-C? -C6 alkyl, N (alkyl), Cj-Ce);!, S02-CH3-COOH, COO- Cx-C6 alkyl, CONH2; R 1 'H, CF 3, CN, COOH, COO-C 1 -C 6 alkyl, CONH 2, CONH- C 1 -C 6 alkyl, CON [C 1 -C 6 alkyl], C 1 -C 6 alkyl, C 2 alkenyl -Cd, C2-C6 alkynyl, 0-Ci-Cß alkyl, where one, more than one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are replaced by fluorine, or a hydrogen is replaced by OH, OC (0) CH3, 0C (0) H, 0-CH2-Ph, NH2, NH-C0-CH3 or N (C00CH2Ph) 2; SO2-NH2, S02NH-alkyl (of C? -C6), S02N [alkyl (of Cx-C6)] 2, S-alkyl (of C? -C6), S- (CH2) nfyl, S0- alkyl ( of C? -C6), SO- (CH2) nfilo, S02-alkyl (of C? -C6), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to twice by F, Cl, Br, OH, CF3, N02, CN, 0CF3, 0- (C? -C6) alkyl, C? -C6 alkyl, NH2; NH2, NH-C-C6 alkyl, N (C6-C6 alkyl) 2, C-C7-NH-acyl, phenyl, CH2-phenyl, it being possible for the phenyl radical to be substituted up to three times by F , Cl, Br, I, OH, CF3, N02, CN, 0CF3, 0- (Ci-Cß) alkyl, C?-C6 alkyl, NH 2, NH-C?-C6 alkyl, N (C-alkyl) ! -C6) 2, S02-CH3-C00H, COO- C? -C6 alkyl, C0NH2; R2 NH2, NHR3, NR4R5 R3 C? -C6 alkyl, CN, CH = NH, C (= S) NH2, C (= NH) -NH-phenyl, it being possible for the phenyl ring to be substituted up to twice by F, Cl, Br, I , OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), Cx-C6 alkyl, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO-C6-C6 alkyl, C0NH2; phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted one to three times by F, Cl, Br, I, OH, N02, CN, 0CF3, O-alkyl (of C2-C6), C2-alkyl CT, NH 2, NH-Ci-Cß N alkyl (C 1 -C 6 alkyl) 2, S 0 2 -CH 3 -COOH, COO-d 6 alkyl, CONH 2; R4 Ci-Ce alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C3-Ce alkynyl, phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted once or twice by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH-alkyl? of C? -C6, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO- C? -C6 alkyl, C0NH2 R5 is Ci-Cß alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted once or twice by F, Cl, Br , I, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH- Ci-Cg alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO-C6-C6 alkyl, C0NH2; or and their physiologically tolerated salts and derivatives with physiological functionality.

Particular preference is given to compounds of formula I in which one or more radical (s) have the following meanings a direct link X CH2 Rl CF3, CN, COOH, COO-alkyl (of C? -C6), CONH2, CONH (C? -C6 alkyl), CON [(C? -C6 alkyl)] 2, Ci-Ce alkyl, alkenyl of C2-Cß, C2-C6 alkynyl, O-C6-C6 alkyl, wherein one or more of one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are substituted by fluorine; S02-NH2, S02NH-alkyl (of C? -C6), S02N [alkyl (of C? ~ C6)] 2, S-alkyl (of C? -C6), S- (CH2) n-phenyl, SO- alkyl (from C? -C6), SO- (CH2) n ~ phenyl, S02-alkyl (from Ci-Cß), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to two times by F, Cl, Br, OH, CF3, N02, CN, OCF3, 0- (C? -C6) alkyl, Ci-Ce alkyl, NH; phenyl, O-phenyl, it being possible for the phenyl ring to be substituted up to three times by F, Cl, Br, I, OH, CF3 / N02, CN, OCF3, O-alkyl (of C? -C6), C-alkyl ? -Cß, NH2, NH-C-C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, C0-C6 COO-alkyl, CONH2; R1 'H, CF3, CN, COOH, COO-C6-C6 alkyl, CONH2, CONH- C6-C6 alkyl, CON [C6-C6 alkyl] 2? C? -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C? -C6 alkyl 0, where one, more than one or all of the hydrogen (s) in the alkyl, alkenyl radicals and alkynyl are replaced by fluorine; S02-NH2, S02NH-alkyl (of C-C6), S02N [alkyl (of C-Ce)] 2, S-alkyl (of C? -C6), S- (CH2) n-phenyl, SO-alkyl ( of C-C6), SO- (CH2) n-phenyl, S02-alkyl (of C? -C6), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to twice by F, Cl, Br, OH, CF3, N02, CN, 0CF3, 0- (C? -C6) alkyl, C? -C6 alkyl, NH2; phenyl, CH2-phenyl, it being possible for the phenyl radical to be substituted up to three times by F, Cl, Br, I, OH, CF3, N02, CN, 0CF3, O-alkyl (of C? -C6), C-alkyl ? -C6, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) 2 / S02-CH3-COOH, COO-C? -C6 alkyl, CONH2; R2 NH2, NHR3, NR4R5 R3 C-C6 alkyl R4 C? -C6 alkyl R5 is C? -Cd alkyl and its physiologically tolerated salts.

The invention also relates to the compounds of the formula I in the form of their racemates, racemic mixtures and pure enantiomers, and to their diastereomers and mixtures thereof. The alkyl, alkenyl and alkynyl radicals in the substituents R1, R1 ', R2, R3, R4 and R5 can be straight-chain or branched. Salts acceptable for pharmaceutical use are particularly suitable for medical applications because of their greater solubility in water compared to the initial compounds on which they are based. These salts must have an anion or cation acceptable for pharmaceutical use. The acid addition salts acceptable for pharmaceutical use of the compounds of the invention are salts of inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric, metaphosphoric, nitric and sulfuric acids, and organic acids such as acetic acid, benzenesulfonic, benzoic, citric, ethanesulfonic, fumaric, gluconic, glycolic, isethionic, lactic, lactobionic, maleic, malic, methanesulfonic acids , succinic, p-toluenesulfonic, tartaric and trifluoroacetic. The use of chloride for medical purposes is particularly preferred. Suitable basic salts acceptable for pharmaceutical use are ammonium salts, alkali metal salts (such as sodium and potassium salts) and alkaline earth metal salts (such as magnesium and calcium salts). ' Salts with an anion not acceptable for pharmaceutical use likewise fall within the scope of the invention as intermediates useful for the preparation or purification of salts acceptable for pharmaceutical use and / or for use in non-therapeutic applications, for example in vitro . The term "derivative with physiological functionality" which is used herein refers to any derivative tolerated in the physiological medium of a compound according to the invention, for example an ester, which can, with administration to a mammal, for example to humans, to form (directly or indirectly) such a compound or an active metabolite thereof. Another aspect of this invention is the prodrugs or prodrugs of the compounds of the invention. Such prodrugs can be metabolized in vivo to a compound of the invention. These prodrugs can be active or not. The compounds of the invention can also exist in different polymorphic forms, for example as amorphous and crystalline polymorphic forms. All polymorphic forms of the compounds of the invention fall within the scope of the invention and are another aspect of the invention. All references that are given below to "compound (s) of the formula (I)" refers to the compound (s) of the formula (I) as already described, and to the salts, solvates and derivatives with physiological functionality thereof as described herein . The amount of a compound of the formula (I) necessary to achieve the desired biological effect depends on various factors, for example the specific compound chosen, the proposed use, the mode of administration and the clinical condition of the patient. In general, the daily dose is in the range of 0.3 mg to 100 mg (usually from 3 mg to 50 mg) per day and per kilogram of body weight, for example 3-10 mg / kg / day. An intravenous dose can be, for example, in the range from 0. 3 mg to 1.0 mg / kg, which can be conveniently administered as an infusion of 10 ng up to 100 ng per kilogram per minute. Suitable infusion solutions for these purposes may contain, for example, from 0.1 ng to 10 mg, usually from 1 ng to 10 mg, per milliliter. The individual doses may contain, for example, from 1 ng to 10 g of the active ingredient, thus, the ampoules for injection may contain, for example, from 1 mg to 100 mg, and the single dose formulations that can be administered via oral, for example as tablets or capsules may contain, for example, from 1.0 to 1000 mg, usually from 10 to 600 mg. In the case of pharmaceutically acceptable salts, the above weight data are based on the weight of the aminothiazole ion derived from the salt. The compounds of the formula (I) can be used for prophylaxis or treatment of the aforementioned states as a compound, but preferably in the form of a pharmaceutical composition with a compatible carrier. The carrier must, of course, be compatible in the sense of compatibility with other ingredients of the composition and should not be detrimental to the health of the patient. The carrier can be a solid or liquid or both and is preferably formulated with the compound as a single dose, for example as a tablet, which can contain from 0.05% to 95% by weight of the active ingredient. Likewise, other active substances for pharmaceutical use may be present, and include other compounds of the formula (I). The pharmaceutical compositions according to the invention can be produced by any of the known pharmaceutical methods which mainly consists in mixing the ingredients with the carriers and / or excipients acceptable for pharmacological use. The pharmaceutical compositions according to the invention are those suitable for oral, rectal, topical, peroral (for example sublingual) and parenteral (for example subcutaneous) administration., intramuscular, intradermal or intravenous) although the most convenient mode of administration depends in each individual case on the nature and severity of the condition being treated and on the nature of the compound of the formula (I) that is used in each case. Coated formulations and coated slow release formulations are also within the scope of the invention. Preferred are acid and gastric fluid resistant formulations, suitable gastric fluid resistant coatings consist of cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropylmethylcellulose phthalate and anionic polymers of methacrylic acid and methyl methacrylate. Convenient pharmaceutical compounds for oral administration may be in the form of separate units such as, for example, capsules, capsules, lozenges or tablets, each of which contains a defined amount of the compound of the formula (I); as powder or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil in water or water in oil emulsion. Can these compositions, as already mentioned, be prepared? by any convenient pharmaceutical method that includes a step in which the active ingredient and the carrier (which may consist of one or more of the additional ingredients) are put in contact. In general, the compositions are produced by uniform and homogeneous mixing of the active ingredient with a liquid carrier and / or finely dispersed solid, after which the product is formed if necessary. Thus, for example, a tablet can be produced by compressing or shaping the powder or granules of the compound, where appropriate, with one or more additional ingredients. Compressed tablets can be produced by tabletting the compound in free flowing form such as, for example, a powder or granules, as appropriate mixed with a binder, lubricant, inert diluent and / or one (or more) surface active agents. / dispersants in a convenient machine. The tablets formed can be produced by forming, in a convenient machine, the compound that is in powder form and moistened with an inert liquid diluent. Pharmaceutical compositions suitable for peroral (sublingual) administration comprise mouth-dissolving tablets which contain a compound of the formula (I), with a flavoring, usually sucrose, and gum arabic or tragacanth, and lozenges containing the compound in an inert base such as gelatin and glycerol or sucrose and gum arabic. Pharmaceutical compositions suitable for parenteral administration comprise preferably sterile aqueous preparations of a compound of the formula (I), which are preferably isotonic with the blood of the proposed recipient. These preparations are preferably administered intravenously, although administration can also take place by subcutaneous, intramuscular or intradermal injection. These preparations can preferably be produced by mixing the compound with water and making the resulting solution sterile and isotonic with the blood. The injectable compositions according to the invention contain, in general, from 0.1 to 5% by weight of the active compound.

Pharmaceutical compositions suitable for rectal administration are preferably in the form of individual dose suppositories. These can be produced by mixing a compound of the formula (I) with one or more of the traditional solid carriers, for example cocoa butter, and shaping the resulting mixture. Pharmaceutical compositions suitable for topical use on the skin are preferably in the form of an ointment, cream, lotion, paste, spray, aerosol or oil. The carriers that may be used sori petrolatum, lanolin, polyethylene glycols, alcohols and combinations of two or more of these substances. The active ingredient, in general, is present in a concentration from 0.1 to 15% by weight of the composition, for example from 0.5 to 2%. Transdermal administration is also possible. Suitable pharmaceutical compositions for transdermal applications may be in the form of individual plasters that are suitable for long-term close contact with the epidermis of the patient. Such plasters conveniently contain the active ingredient in an aqueous solution which is buffered as appropriate, dissolved and / or dispersed in an adhesive or dispersed in a polymer. A convenient concentration of the active ingredient is about 1% up to 35%, preferably about 3% up to 15%. As a particular option, the active ingredient • can be released by electrotransport or iontophoresis as described, for example, in Pharmaceutical Research, 2 (6): 318 (1986). The invention also relates to a process for the preparation of the compounds of the general formula (I), which consists of preparing the compounds of the general formula I according to the following reaction scheme: Reaction scheme 1: The bicyclic ketones of the formula II in which R1, R1 ', X and Y have the stated meanings are available commercially or can be prepared by the methods known from the literature. The bicyclic ketones of the formula II in which R1 or R1 'are aryl radicals can be obtained by the Pd (0) catalyzed addition of boric esters to compounds of the formula II in which R1 and / or R1' are bromine, iodine or trifluoromethylsulphonyloxy (for example: N. Miyaura and A. Suzuki, Chem. Rev. 95, 2457-83 (1995) or T. Oh-e, N. Miyaura and A. Suzuki, J. Org. Chem. 58, 2201-08 (1993)). The bicyclic ketones of the general formula II in which R1 and / or R1 'are alkynyl radicals or alkenyl radicals can be prepared, for example, by methods such as those described by K. Sonagashira et al., Tetrahedron Lett. 4467 (1975) and S. Takahaschi et al., Synthesis 627 (1980) (palladium-catalyzed reaction of, for example, trimethylsilylacetylene or alkynes) or by E. Negishi et al., J. Org. Chem. 62, 8957-60 (1997) (alkynyl zinc bromide) or by A. Hassner et al., J. Org. Chem. 49, 2546 (1984) (trialkylstannylalkynes, trialkylstannylvinyl or allyl compounds, 1-alkenylboron compounds or vinyl compounds). The bicyclic ketones of the general formula II are activated mainly by a reaction with bromine to obtain the alpha-bromo ketone of the general formula III (Z = Br). Z in the activated compounds of the general formula III can, however, also conveniently be Cl, I, OC (O) -C6H-4-N02, 0-S02-CH3, 0-S02-CF3, 0-S02-C6H -4-CH3 or 0-S02-C6H5. The compounds of the general formula I x HZ- are obtained by the reaction of the thioureas of the general formula IVa or IVb in which R 2 = NH 2, NHR 3 or R 2 = NR 4 R 5, and the radicals R 2, R 3, R 4 and R 5 have the established meanings. The procedure for this is, conveniently, such that the compounds III react with the thioureas IVa or IVb in the molar ratio from 1: 1 to 1: 1.5. The reaction is conveniently carried out in an inert solvent, for example, in polar organic solvents such as dimethylformamide, dimethylacetamide, 2-methyl-2-pyrrolidone, dimethyl sulfoxide, dioxane, tetrahydrofuran, acetonitrile, nitromethane or diethylene glycol dimethyl ether. However, the solvents which appear to be particularly advantageous are methyl acetate and ethyl acetate, short-chain alcohols such as methanol, ethanol, propanol, isopropanol, and lower dialkyl ketones such as acetone, 2-butanone or 2-hexanone. It is also possible to use mixtures of the mentioned reaction media; thus, it is also possible to use mixtures of the aforesaid solvents with solvents which are less convenient per se, such as, for example, mixtures of methanol, with benzene, ethanol with toluene, methanol with diethyl ether or with tert-butyl methyl ether, ethanol with tetrachloromethane, acetone with chloroform, dichloromethane or 1,2-dichloroethane, it being convenient that the most polar solvent in each case be used in excess. The reactants may be present in suspension or solution in the particular reaction medium. It is also possible in principle that the reactants react without a solvent, especially when the particular thioamide has a low melting point. The reaction is only slightly exothermic and can be carried out between -10 ° C and 150 ° C, preferably between 50 ° C and 100 ° C. A temperature range between 50 ° C and 80 ° C usually proves to be particularly favorable.

The reaction time depends mainly on the reaction temperature and is between 2 minutes and 3 days at higher and lower temperatures, respectively. In the favorable temperature range, the reaction time is usually between 5 minutes and 48 hours. The resulting salts of the compounds of the general formula x HZ and Ib x HZ can be converted with organic or inorganic bases into the free basic compounds of the formula I (la: R2 = NH2, NHR3; Ib: R2 = NR4R5). The compounds of the general formula I can be converted into their acid addition salts of the general formula I x HB by reaction with organic or inorganic acids of the formula HB. Examples of suitable inorganic HB acids are: hydrohalic acid such as hydrochloric acid and hydrobromic acid, and sulfuric acid, phosphoric acid and sulfamic acid. Examples of the organic acids HB that may be mentioned are: formic acid, acetic acid, benzoic acid, p-toluenesulfonic acid, benzenesulfonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, tartaric acid, citric acid, L-acid ascorbic acid, salicylic acid, isethionic acid, methanesulfonic acid, trifluoromethanesulfonic acid, 1,2-benzisothiazol-3 (2H) -one, 2,2-dioxide 6-methyl-l, 2,3-oxatiazin-4- (3H) -one In addition to the derivatives described in the examples, according to the invention, the compounds of the formula I, and their acid addition products, are also obtained, which are compiled in the following tables: Table 1: Examples R1"Formula I The compounds of formula I are distinguished by their beneficial effects on lipid metabolism, and are particularly suitable as anorectic agents. The compounds can be used alone or in combination with other anorectic active ingredients. Other anorectic active ingredients of this type are mentioned, for example, in Rote Liste, chapter 01 in weight reducing agents / appetite suppressants. The compounds are suitable for prophylaxis and, in particular, for the treatment of obesity. The compounds are also suitable for prophylaxis and, in particular, for the treatment of type II diabetes. The activity of the compounds was tested as follows: Biological test model The anorectic effect was tested in male NMRI mice. After abstaining from food for 24 hours, the test product was administered by priming. The animals were caged individually and had free access to drinking water and 30 minutes after the administration of the product they were offered condensed milk. The consumption of condensed milk was determined and the general behavior of the animals was inspected every half hour for 7 hours. The milk consumption measured was compared with that of untreated control animals.

Table 2: Anorectic effect measured by reduction in cumulative milk consumption by treated animals compared to untreated animals The examples detailed below serve to illustrate the invention, however, without restricting it. The established decomposition points are not corrected and generally depend on the heating rate.

Example of procedure 1: 2-Dimethylamino-8H-indene [1, 2-d] thiazoi-β-carbonitrile bromide (compound of Example 02): a) l-oxoindan-5-carbonitrile 95 g of 5-bromo-l-indanone and 4.93 g of CuCN are suspended in 19 ml of dimethylformamide and boiled under reflux for 4 hours. A solution of 18 g of iron (III) chloride in 5 ml of concentrated hydrochloric acid with 30 ml of water is added dropwise to the cold, dark brown viscous suspension with stirring, and the mixture is then stirred at 70 ° C for 30 minutes. The reaction mixture is extracted by stirring three times with 50 ml of toluene, and the combined organic phases are extracted by stirring with 50 ml of 2N hydrochloric acid and 50 ml of 2N sodium hydroxide solution and then washed with water until neutral . The toluene extract is dried over magnesium sulfate and concentrated in vacuo, and the residue is recrystallized from N-heptane. L-Oxoindan-5-carbonitrile with a melting point of 123-125 ° C is obtained. 2-bromo-l-oxoindan-5-carbonitrile I joke l-oxoindan-5-carbonitrile with bromine in glacial acetic acid with addition of a catalytic amount of 48% concentration of HBr solution in water and produce 2-bromo-l-oxoindan-5-carbonitrile with a melting point 115-118 ° C. c) 2-Dimethylamino-8H-inden [1,2-d] thiazole-6-carbonitrile Bromhydrate 236 mg of 2-bromo-l-oxoindan-5-carbonitrile are heated under reflux with 156. mg of N, N-dimethylthiourea in 10 ml of triacetone for 3 hours. The reaction mixture is concentrated in vacuo; the residue is stirred with little acetone, filtered with suction, washed with acetone and dried in vacuo. 2-Dimethylamino-8H-indene [1,2-d] thiazole-6-carbonitrile hydrobromide with a melting point > 300 ° C.

Example of procedure 2 -methanesulfonyl-8H-indeno [1,2-d] thiazol-2-ylamine hydrochloride (compound of Example 03) Hydrochloride of. 2-amino-5-methanesulfonyl-8,8a-dihydroindeno [1,2-d] thiazole-3a-ol 2. 3 g of 2-bromo-6-methanesulfonyl-1-indanone are dissolved in 50 ml of acetone and, with stirring, 0.67 g of thiourea is added. The solution is initially clear but, after a few minutes, the hydrobromide of the closed ring compound crystallizes. After stirring at room temperature for 4 hours, the solid is filtered off with suction and dissolved in about 30 ml of methanol, and 1 ml of triethylamine is added. Once again, the precipitation begins after a few minutes. After 15 minutes 150 ml of water is added, and the formation of the product is completed by stirring at room temperature. The precipitate is filtered with suction, washed with water and dried with air. The solution in ethyl acetate, the addition of ethereal hydrochloric acid, the filtration of the product which is formed with suction and the drying under vacuum gives the hydrochloride of 2-amino-5-methanesulfonyl-8,8a-dihydroindeno [1, 2- dithiazole-3a-ol with decomposition point of 241 ° C. b) Hydrochloride of. 5-methanesulfonyl-8H-indene [1,2-d] thiazol-2-ylamine 1 g of the compound obtained in a) is stirred in 100 ml of 50% concentrated hydrochloric acid at room temperature for 10 hours, and the product is filtered off with suction and washed briefly with cold water. D-methanesulfonyl-dH-1-indene [1,2-d] thiazol-2-yl-amine hydrochloride with a melting point of 230 ° C is obtained.

Preparation example 3 6-Chloro-5-methanesulfonyl-8H-indene [1, 2-d] thiazol-2-ylamine hydrochloride (compound of Example 05) 6-Chloro-5-methanesulfonyl-8H-indene [1,2-d] thiazol-2-ylamine hydrochloride, melting point > 260 ° C is obtained in the above-described manner starting from 2-bromo-5-chloro-6-methanesulfonyl-1-indanone.

Example of procedure 4 Methyl [6- (2, 2, 3, 3, 3-pentafluoropropoxy) -8H-indene [1, 2-d] thiazol-2-yl] amine hydrochloride (compound of Example 08) a) 5- (2, 2, 3, 3, 3-pentafluoropropoxy) -1-indanone 6. 5 g of 5-fluoro-1-indanone are dissolved in 50 ml of anhydrous dimethylacetamide and, after the addition of 36.5 g of crushed potassium carbonate, anhydrous and 12.9 g of 2, 2, 3, 3, 3-pentafluoropropanol, Stir at 95-100 ° C for 10 hours. The solvent is then removed by distillation in vacuo; 300 ml of water are added to the residue, and the aqueous phase is extracted with ethyl acetate several times. The organic phase is washed with water, dried over sodium sulfate and concentrated in vacuo. Purification on silica gel produces 5- (2, 2, 3, 3, 3-pentafluoropropoxy) -1- indanone as a brown oil which crystallizes after some time; melting point 52-54 ° C. b) 2-bromo-5- (2,2,3,3, 3-pentafluoropropoxy) -1-indanone 6. 9 g of 5- (2, 2, 3, 3, 3-pentafluoropropoxy) -1-indanone are dissolved in 100 ml of ethyl acetate, and a solution of 3.9 g of bromine in 15 milliliters of acetate is added dropwise. of ethyl. The solution is heated briefly to reflux before adding the rest of the bromine solution dropwise. This is then stirred at room temperature for 2 hours. The reaction solution is concentrated in vacuo and produces 2-bromo-5- (2, 2, 3, 3, 3-pentafluoropropoxy) -1-indanone as an oil which is used without purification in the next step.

Methyl [6- (2, 2, 3, 3, 3-pentafluoropropoxy) -8H-indeno [1, 2-d] thiazol-2-yl] amine hydrochloride 1. 79 g of 2-bromo-5- (2, 2, 3, 3, 3-pentafluoropropoxy) -1-indanone are dissolved in 60 ml of ethyl acetate, and a solution of 450 mg of N-methylthiourea in 20 ml is added. ml of acetate / ethyl. The reaction solution is stirred at room temperature for 7 hours; The pale precipitate is filtered off with suction and washed with ethyl acetate and then dried. The resulting hydrobromide is dissolved in 60 ml of methanol and, after the addition of 1.53 g of triethylamine, is stirred at room temperature for 5 hours. The solution is concentrated; the residue crystallizes with the addition of water. The dried free base is dissolved in ethyl acetate, ethereal HCl solution is added until the reaction is acidic. After 3 hours at room temperature, the crystals that formed are filtered off with suction and dried under vacuum. To prepare the unsaturated system, the dried crystals are heated to reflux in 35 ml of glacial acetic acid for 2 hours. The solvent is distilled in vacuo and the solid residue is stirred with diisopropyl ether, filtered with suction and dried in vacuo. Methyl [6- (2,2,3,3,3,3-pentafluoropropoxy) -8H-indene [1,2-d] thiazol-2-yl] amine hydrochloride with a melting point of 258 ° C is obtained.

Example of procedure 5 Methyl (6-pyridin-3-yl-8H-indene [1, 2-d] thiazol-2-yl] amine hydrochloride (compound of Example 16) a) 5-pyridin-3-yl-l-indanone 13. 26 g of 3-bromopyridine are dissolved in 160 ml of diethyl ether and cooled to -60 ° C. To this solution, 52 ml of a 1.6 molar solution of n-butyl lithium in n-hexane is added dropwise over the course of 30 minutes. The solution is allowed to warm to -30 ° C and, at this temperature, 9.5 ml of trimethyl borate is added dropwise with stirring. Subsequently, the reaction mixture is refluxed for 3 hours and then cooled to 0 ° C, and 6.1 ml of 1,3-propanediol are added dropwise. This mixture is stirred at 0 ° C for 30 minutes before adding 5.46 ml of methanesulfonic acid dropwise and with stirring for another 30 minutes. Then 20 g of Celite is added, the mixture is warmed to room temperature and filtered, the filtrate is concentrated, the residue is stirred with 700 ml of toluene and, after renewed filtration, the solvent is distilled off in vacuo. 4.1 g of the residue _ (3- [1, 3, 2] dioxaborinan-2-ylpyridine) are dissolved, without further purification, together with 4.22 g of 5-bromo-l-indanone and 4.24 g of sodium carbonate in a mixture of 100 ml of toluene with 20 ml of ethanol and 20 ml of water. The solution is degassed with argon and then 112 mg of palladium (II) acetate and 262 mg of triphenylphosphine are added. The reaction mixture is refluxed for 4 hours and cooled to room temperature, and the ethanol content in the mixture is removed by vacuum distillation. Then 50 ml of 0.5 N sodium hydroxide solution is added with stirring, the organic phase is separated and the aqueous phase is extracted by stirring with toluene. The combined organic phases are extracted by successively stirring with water and saturated brine, dried over magnesium sulfate, concentrated in vacuo and purified by chromatography on silica gel with ethyl acetate / n-heptane 1/1. There is obtained 5-pyridin-3-yl-l-indanone with a melting point of 103-106 ° C. 2-chloro-5-pyridin-3-yl-1-indanone 3. 22 g of 5-pyridin-3-yl-l-indanone are dissolved in 160 ml of dichloromethane and, at 0 ° C, a solution of 1.34 ml of sulfuryl chloride in 40 ml of dichloromethane is added dropwise during the course 15 minutes. After stirring at 0 ° C for 30 minutes and then at room temperature for 60 minutes, 50 ml of a saturated solution of sodium bicarbonate is slowly added. The organic phase is separated, washed with water, dried over magnesium sulfate, concentrated in vacuo and purified by chromatography on silica gel with dichloromethane / methanol 50/1. 2-Chloro-5-pyridin-3-yl-l-indanone is obtained with a melting point of 103-105 ° C (in addition to 2,2-dichloro-5-pyridin-3-yl-l-indanone with a melting point of 109 ° C). c) Methyl- (6-pyridin-3-yl-8H-indene [1, 2-d] thiazol-2-yl) amine hydrochloride 366 mg of 2-chloro-5-pyridin-3-yl-l-indanone are dissolved with 203 mg of N-methylthiourea in 5 ml of methanol and heated to reflux for 7 hours. The reaction mixture is cooled and, after the addition of 20 ml of acetone, the precipitate is filtered off with suction, washed with acetone and dried in vacuo. Methyl (6-pyridin-3-yl-8H-indene [1,2-d] thiazol-2-yl) amine hydrochloride with a melting point of 225 ° C is obtained.

Example of procedure 6 6-M-Tolyloxy-8H-indene [1,2-d] thiazol-2-yl-amine hydrochloride (compound of Example 17) - . 5-m-tol i loxi-1-indanone 5 g of 5-fluoro-l-indane [sic] are dissolved in 50 ml of anhydrous dimethylformamide, and 18.2 g of anhydrous potassium carbonate, powder and 3.57 g are added. of m-cresol. The reaction mixture is stirred at 110 ° C for 6 hours. The solvent is distilled off in vacuo and the residue is mixed with 100 ml of water and stirred for 2 hours. The aqueous residue is extracted with ethyl acetate, and the organic extract is washed three times with water, dried over sodium sulfate, filtered and concentrated in vacuo. 5-m-tolyloxy-l-indanone is obtained as brown oil which is subsequently reacted without purification. b) 2-bromo-5-m-tolyloxy-l-indanone The bromination of 5-m-tolyloxy-l-indanone takes place in the same manner as the bromination of 5- (2, 2, 3, 3, 3-pentafluoropropoxy) -1-indanone (Example 4) and produces 2-bromine -5-m-tolyloxy-l-indanone as a pale brown oil. c) β-m-tolyloxy-8H-indene [1, 2-d] thiazol-2-ylamine hydrochloride 1.4 g of the above bromoketone is dissolved in 14 ml of acetone and, after the addition of 340 mg of thiourea in 20 ml of acetone, stir at room temperature for 7 hours. The crystals of 2-amino-6-m-tolyloxy-8,8a-dihydroindeno [1,2-d] thiazole-3a-ol hydrobromide which were separated are filtered off with suction and dried in vacuo. As described in Example 4, this bromhydrate? it also becomes the free base and also the hydrochloride. The 2-amino-6-m-tolyloxy-8,8a-dihydroindeno [1,2-d] thiazole-3a-ol hydrochloride is suspended in 30 ml of glacial acetic acid and heated to reflux with stirring. After 2 hours, the solution is concentrated in vacuo, and the residue is stirred with diisopropyl ether, filtered with suction and dried in vacuo. The 6-m-tolyloxy-8H-indene [1,2-d] thiazol-2-ylamine hydrochloride with a melting point of 174 ° C is obtained.

Claims (6)

1. A compound of the formula I is a direct link, CH2, CH2-CH2 X is CH2, O R1 is CF3, CN, COOH, COO-alkyl (of C? -C6), CONH2, CONH (C? -C6 alkyl), CON [(C? -C6 alkyl)] 2, C? -C6 alkyl , C2-C6 alkenyl, C2-C6 alkynyl / O-Ci-Cß alkyl, where one or more of one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are substituted by fluorine or a hydrogen is substituted by OH, OC (0) CH3, OC (0) H, 0-CH2-Ph, NH2, NH-CO-CH3 or N (C00CH2Ph) 2; S02-NH2, S02NH-alkyl (of C? -C6), S02N [alkyl (of C? ~ C6)] 2, S-alkyl (of C? -C6), S- (CH2) nfyl, S0- alkyl (of C? -C6), SO- (CH2) nfilo, S02-alkyl (of Ci-Cß), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to twice by F, Cl, Br, OH, CF3, N02, CN, 0CF3, 0-alkyl (of Ci-Cß), Ci-Ce alkyl, NH2; NH 2, NH-C 1 -C 6 alkyl, N (C 1 -C 6 alkyl) 2, C 1 -C 7 NH-acyl, phenyl, biphenylyl, 0- (CH 2) n -phenyl, where n can be 0- 6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl, it being possible for the phenyl, biphenylyl, naphthyl, pyridyl, furanyl and thienyl rings each one is substituted up to three times by F, Cl, Br, I, OH, CF3, N02, CN, 0CF3, O-alkyl (of C; -C6), C? -C6 alkyl, NH2, NH-Cx alkyl -Ce, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO-C? -C6 alkyl, C0NH2; 1,2,3-triazol-5-yl, it being possible for the triazole ring to be substituted at the 1, 2 or 3 position by methyl or benzyl; tetrazol-5-yl, it being possible for the tetrazole ring to be substituted in the 1 or 2 position by methyl or benzyl R1 'is H, CF3, CN, COOH, COO-C6-C6 alkyl, CONH2, CONH-alkyl C? -C6, CON [C? -C6 alkyl], C1-C0 alkyl, C2-C6 alkenyl, C2-Ce alkynyl, C1-C6 alkyl, where one or more than one or all the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are replaced by fluorine, or a hydrogen is replaced by OH, 0C (0) CH3, 0C (0) H, 0-CH2-Ph, NH2, NH -C0-CH3 or N (C00CH2Ph) 2; S02-NH2, S02NH-alkyl (of C? -C6), S02N [alkyl (of Cx- C6)] 2, S-alkyI (of C? -C6), S- (CH2) n-phenyl, S0- alkyl (of C? -C6), SO- (CH2) n-phenyl, S02-alkyl (of Ci-Cß), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to two times by F, Cl, Br, OH, CF3, N02, CN, OCF3, 0- (C? -C6) alkyl, C? -C6 alkyl, NH2; NH 2, NH-C 1 -C 6 alkyl, N (C 1 -C 6 alkyl) 2, C 1 -C 7 -Nacyl, phenyl, biphenylyl, 0- (CH 2) n -phenyl, where n can be 0-6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl, it being possible for the phenyl, biphenylyl, naphthyl, pyridyl, furanyl and thienyl each is substituted up to three times by F, Cl, Br, I, OH, CF3, N02, CN, 0CF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH-alkyl of CL-C6, N (C? -C6 alkyl) 2, S02-CH3-C00H, COO-C? -C6 alkyl, CONH2; 1,2,3-triazol-5-yl, it being possible for the triazole ring to be substituted at the 1, 2 or 3 position by methyl or benzyl; tetrazol-5-yl, it being possible that the ring tetrazole is substituted in the 1 or 2 position by methyl or benzyl R2 is NH2, NHR3, NR4R5 R3 is C6-C6 alkyl, CN, CH = NH, C (= S) NH2, C (= NH) -NH-phenyl, it being possible for the phenyl ring to be substituted up to two times by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO-C de-C6 alkyl, CONH2; phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted up to three times by F, Cl, Br, I, OH, N02, CN, OCF3, O- (C2-C6) alkyl, C2-C6 alkyl, NH2, NH-C-C6 alkyl, N (C-C6 alkyl) 2, S02-CH3-COOH, COO-C6-C6 alkyl, CONH2; biphenylyl, 1- o. 2-naphthyl, 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl, 5-tetrazolyl, it being possible for the biphenylyl, naphthyl, pyridyl, furanyl or thienyl rings each to be substituted up to twice by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH-C? -C6 alkyl, N (C-alkyl) ? -C6) 2, S02-CH3-COOH, COO-C? -C6 alkyl, CONH2; CH2-phenyl, CH2-2-pyridyl or CH2-4-pyridyl, it being possible for the phenyl or pyridyl ring to be substituted once or twice by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O -alkyl (from C? -C6), C? -C6 alkyl, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO-C-alkyl ? -C6, CONH2 is C? -C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted once or twice by F, Cl, Br , I, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) ) 2, S02-CH3-COOH, COO-C6-C6 alkyl, CONH2 R5 is C6-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, phenyl, CH2- phenyl, it being possible for the phenyl ring to be substituted once or twice by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl , NH2, NH- C- C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, C0-C6 COO-alkyl, CONH2; or R4 and R5 together form one of the groups CH2-CH2-CH2-CH2-CH2, CH2-CH2-N (CH3) CH2-CH2, CH2-CH2- N (CH2-phenyl) CH2-CH2, CH2-CH2-0 -CH2-CH2, CH2-CH2-CH2-CH2 and their physiologically tolerated salts and derivatives with physiological functionality.

2. A compound of the formula I as claimed in claim 1 wherein the meanings are as follows: Y a direct bond, CH2, CH2-CH2 X CH2, 0 Rl CF3, CN, COOH, COO-alkyl (from Cj-C6), CONH2, CONH (C? -C6 alkyl), CON [(C1-C6 alkyl)] 2, C? -C6 alkyl, C2-C6 alkenyl, C2-C alkynyl, O-C? -C6 alkyl, where one or more of one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are substituted by fluorine or a hydrogen is substituted by OH, OC (0) CH3, OC (0) H, 0- CH2-Ph , NH2, NH-C0-CH3 or N (C00CH2Ph) 2; S02-NH2, S02NH-alkyl (of C? -C6), S02N [alkyl (of Cx-Ce)] 2, S-alkyl (of C? -C6), S- (CH2) n-phenyl, SO? alkyl (of C-C6), SO- (CH2) n ~ phenyl, S02-alkyl (of C? -C6), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to two times by F, Cl, Br, OH, CF3, N02, CN, OCF3, 0- (C-C6) alkyl, C? -C6 alkyl, NH2; NH2, NH-Cx-Ce alkyl, N (C? -C6 alkyl) 2, C? -C7 NH-acyl, phenyl, O-phenyl, it being possible for the phenyl ring to be substituted up to three times by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O- (C? -C6) alkyl, C? -C6 alkyl, NH2, NH-C-C6 alkyl, N (C? -C6) 2, S02-CH3-COOH, COO- C6alkyl, C0NH2; R1 'H, CF3, CN, COOH, COO-C6-C6 alkyl, CONH2, CONH- Ci-Ce alkyl, CON [C6-C6 alkyl], C6-C6 alkyl, C2-alkenyl -C6, C2-C6 alkynyl, O-C6-C6 alkyl, where one, more than one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are replaced by fluorine, or a hydrogen is replaced by OH, 0C (0) CH3, OC (0) H, 0-CH2-Ph, NH2, NH-CO-CH3 or N (COOCH2Ph) 2; S02-NH2, S02NH-alkyl (from C? -C6), S02N [alkyl (from C? ~ C6)] 2, S-alkyl (from C-C6), S- (CH2) n-phenyl, SO-alkyl (of C? -C6), SO- (CH2) n-phenyl, S02-alkyl (of C? -C6), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to two times by F, Cl, Br, OH, CF3, N02, CN, 0CF3, 0-alkyl (of Ci-Ce), C? -Ce alkyl, NH2; NH 2, NH-C 1 -C 6 alkyl, N (C 1 -C 6 alkyl) 2, C 1 -CN-acyl, phenyl, CH 2 -phenyl, it being possible for the phenyl radical to be substituted up to three times by F , Cl, Br, I, OH, CF3, N02, CN, 0CF3, 0-alkyl (from C? -Ce), C? -C6 alkyl, NH2, NH-alkyl from C? -C6, N (alkyl) of C? -C6) 2, S02-CH3-COOH, COO-C? -C6 alkyl, C0NH2; NH2, NHR3, NR4R5 R3 C? -C6 alkyl, CN, CH = NH, C (= S) NH2, C (= NH) -NH phenyl, it being possible that the phenyl ring is substituted up to two times by F, Cl , Br, I, OH CF3, N02, CN, OCF3, O-alkyl (of C? -C6), alkyl dC? -C6, NH2, NH-alkyl of C? -C6, N (C? C6) 2 SO2-CH3-COOH, COO-C6-C6 alkyl, CONH2; phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted by one to three times by F, Cl, Br, I, OH, N02, CN, CF3, O-C2-C6 alkyl, C2-alkyl C6, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, COO-C? -C6 alkyl, CONH2; R 4 C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, C 3 -C 6 alkynyl, phenyl, CH 2 -phenyl, it being possible for the phenyl ring to be substituted twice by F, Cl, Br, I, OH, CF3, N02 / CN, OCF3, O-alkyl (of C? -C6), C? -C6 alkyl, NH2, NH-C? -C6 alkyl, N (C-C6 alkyl) 2 , S02-CH3-COOH, COO C-C6 alkyl, CONH2 R5 is C6-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C3-C6 alkynyl, phenyl, CH2-phenyl, it being possible for the phenyl ring to be substituted once or twice by F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (of • C? -C6), C-C6 alkyl, NH2, NH- C? -C6 alkyl, N (C? C6) 2, S02-CH3-COOH, COO-C6-C6 alkyl, CONH2; or and their physiologically tolerated salts and derivatives with physiological functionality.

3. A compound of formula I as claimed in claim 1 or 2, wherein the meanings are as follows: And a direct link X CH2 Rl CF3, CN, COOH, COO-alkyl (of C? -C6), CONH2, CONH (C? -C6 alkyl), CON [(C? -C6 alkyl)] 2, C? -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C-Ce O-alkyl, wherein one or more of one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are substituted by fluorine; S02-NH2, S02NH-alkyl (of C? -C6), S02N [alkyl (of Cx-Ce)] 2, S-alkyl (of C? -C6), S- (CH2) nfyl, SO-alkyl ( of C? -C6), SO- (CH2) nfenyl, S02-alkyl (of C? -C6), S02- (CH2) nfenyl, where n can be 0-6 and the phenyl radical can be substituted up to two times by F, Cl, Br, OH, CF3, N02, CN, OCF3, 0- (C? -C6) alkyl, C? -C6 alkyl, NH2; phenyl, O-phenyl, it being possible for the phenyl ring to be substituted up to three times by F, Cl, Br, I, OH, CF3, N02, CN, 0CF3, 0-alkyl (of C? -C6), C-alkyl -C6, NH2, NH-C-C6 alkyl, N (C6-C6 alkyl), S02-CH3-C00H, COO-C6-C6 alkyl, C0NH2; R 1 'H, CF 3, CN, COOH, COO-C 1 -C 6 alkyl, CONH 2, CONH- C 1 -C 6 alkyl, CON [C 1 -Ce alkyl] 2 / C 1 -Ce alkyl, alkenyl C2-C6, C2-C6 alkynyl, 0-Cx-Cß alkyl, wherein one, more than one or all of the hydrogen (s) in the alkyl, alkenyl and alkynyl radicals are replaced by fluorine; S02-NH2, S02NH-alkyl (from C? -C6), S02N [alkyl (from Cx-Ce)] 2, S-alkyl (from C? -Ce), S- (CH2) n-phenyl, S0-alkyl (of Cx-Cß), SO- (CH2) n-phenyl, S02-alkyl (of Cx-Ce), S02- (CH2) n-phenyl, where n can be 0-6 and the phenyl radical can be substituted up to twice by F, Cl, Br, OH, CF3, N02, CN, OCF3, 0- (C? -C6) alkyl, C? -C6 alkyl, NH2; phenyl, CH2-phenyl, it being possible for the phenyl radical to be substituted up to three times by F, Cl, Br, I, OH, CF3, N02, CN, 0CF3, O-alkyl (of C? -C6), C? -C6, NH2, NH-C? -C6 alkyl, N (C? -C6 alkyl) 2, S02-CH3-COOH, C0-C6 COO-alkyl, CONH2; R2 NH2, NHR3, NR4R5 R3 Ci-Ce alkyl R4 C? -C6 alkyl R5 is C6-C6 alkyl and its physiologically tolerated salts.

4. A pharmaceutical composition containing one or more compounds as claimed in one or more of claims 1 to 3.

5. A pharmaceutical composition containing one or more compounds as claimed in one or more of claims 1 to 3 and one or more anorectic active ingredients.

6. A process for producing a pharmaceutical composition containing one or more compounds as claimed in one or more of claims 1 to 3, which consists of mixing the active ingredient with a convenient pharmaceutical carrier, and converting this mixture into a convenient form for the administration.