MXPA99008736A - Tetrahydropyrido compounds - Google Patents

Abstract

Compounds of formula (I) in which the substituents have the meanings mentioned in the description, are suitable for the prevention and treatment of gastrointestinal diseases.

Description

TETRAHYDROPYRIDINE COMPOUNDS Field of the Invention The invention relates to new compounds, which are used in the pharmaceutical industry as active materials for the preparation of medicaments. Known technical foundations In the U.S. patent no. 4,468,400 describe midazo [tricyclic 1,2-ajpyridines with different ring systems fused to the basic nucleus of imidazopyridine, which are suitable for the treatment of peptic ulcer diseases. DESCRIPTION OF THE INVENTION The object of the invention are compounds of the formula I wherein R 1 signifies C 1-4 alkyl, R 2 means C 1-4 alkyl or hydroxy C 1-4 alkyl, R 3 signifies hydrogen or halogen, one of substituents R 4a and R 4b signifies hydrogen, and the other signifies hydrogen, hydroxy, C 1 alkoxy -4, C 1-4 alkoxy-C 1-4 alkoxy or C 1-4 alkylcarbonyloxy, or in which R 4a and R 4b together represent O (oxygen), one of the substituents R 5a and R 5b means hydrogen and the other means hydrogen, hydroxy, C 1-4 alkoxy, C 1-4 alkoxy-C 1-4 alkoxy or C 1-4 alkylcarbonyloxy, or in which R 5a and R 5b together represent O (oxygen), or in which one of the substituents R 4a and R 4b by part and one of the substituents R5a and R5b on the other hand mean in each case hydrogen and the other substituents in each case together form a methylenedioxy radical (-O-CH2-O-) or an ethylenedioxy radical (-0-CH2-CH2- O-), where R 4a, R 4b, R 5 and R 5b do not simultaneously have the meaning of hydrogen, R 6 means hydrogen, halogen, C 1-4 alkyl, C 1-4 alkoxy, alkoxy C 1-4 carbonylamino, C 1-4 alkoxy C 1-4 alkoxycarbonylamino or trifluoromethyl and R 7 means hydrogen, halogen, C 1-4 alkyl or C 1-4 alkoxy, and their salts. C 1-4 alkyl represents radical is straight chain alkyl or branched with 1 to 4 carbon atoms. For example. The butyl, isobutyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl and methyl radicals may be mentioned. The methyl radical is preferred.

Hydroxy-C 1-4 alkyl represents C 1-4 alkyl radicals mentioned above, which are substituted with a hydroxy group. For example, hydroxymethyl, 2-hydroxyethyl and 3-hydroxypropyl radicals may be mentioned. The hydroxymethyl radical is preferred. In the sense of the invention, halogen is bromine, chlorine and fluorine. C1-4 alkoxy represents radicals which, in addition to the oxygen atom, contain a straight or branched chain alkyl radical with 1 to 4 carbon atoms. For example, butoxy, isobutoxy, sec-butoxy, tert-butoxy, propoxy, isopropoxy, and preferably the ethoxy and methoxy radicals may be mentioned. C1-4 alkoxy-C1-4 alkoxy represents one of the alkoxy radicals C1-4 mentioned above, which is substituted with an additional C1-4 alkoxy radical. For example, the radicals 2- (methoxy) ethoxy (CH3-0-CH2-CH2-0-) and 2- (ethoxy) ethoxy (CH3-CH2-0-CH2-CH2-0-) can be mentioned. C1-4alkyloxycarbonyloxy represents a carbonyloxy group, to which one of the aforementioned C1-4alkyl radicals is attached. For example, the acetoxy radical C 1 -4 -alkoxycarbonyl represents a carbonyl group, to which one of the aforementioned C 1-4 alkoxy radicals is attached. For example, the methoxycarbonyl radicals (CH3O-C (0) -) and ethoxycarbonyl (CH3CH20-C (0) -) may be mentioned.

C 1 -4 -alkoxycarbonylamino represents an amino radical that is substituted with one of the aforementioned C 1-4 -alkoxycarbonyl radicals. For example, the ethoxycarbonylamino and methoxycarbonylamino radicals may be cited. C 1-4 -alkoxy-C 1-4 -alkoxycarbonyl represents a carbonyl group to which is attached one of the C 1-4 -alkoxy-C 1-4 -alkoxy radicals mentioned above. For example, the 2- (methoxy) ethoxycarbonyl radical (CH3-0-CH2CH2-0-CO-) and 2- (ethoxy) ethoxycarbonyl (CH3CH2-0-CH2CH2-0-CO) may be mentioned. C 1-4 -alkoxy-C 1-4 -alkoxycarbonylamino represents an amino radical that is substituted with one of the C 1-4 -alkoxy-C 1-4 -alkoxy radicals mentioned above. For example, the 2- (methoxy) ethoxycarbonylamino and 2- (ethoxy) ethoxycarbonylamino radical can be mentioned. As salts of the compounds of the formula I - according to the substitution -, all acid addition salts can be taken into account first of all. Particular mention will be made of the pharmacologically compatible salts of the inorganic and organic acids usually employed in galenics. As such, water-insoluble and soluble acid addition salts with acids such as for example hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, are suitable. - (4-hydroxybenzoyl) -benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, lauric acid. malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid, where the acids are used for the preparation of the salt - can be treated , depending on the circumstances, of a monobasic or polybasic acid and depending on which salt is desired - in equimolar quantitative relation or in a different relation thereof. The pharmacologically incompatible salts, which can first be produced, for example, in the preparation of the compounds corresponding to the invention on an industrial scale as process products, are processed by processes known to those skilled in pharmacologically compatible salts. It is known to those skilled in the art that the compounds corresponding to the invention, as well as their salts, when they are isolated, for example in crystalline form, can contain different amounts of solvents. The invention also encompasses, therefore, all solvates and particularly all hydrates of the compounds of the formula I, like all solvates and particularly all hydrates of the salts of the compounds of the formula I. The compounds of the formula I They have three centers of chirality. Object of the invention are the eight imaginable stereoisomers in any mixing ratio with each other, including the pure enantiomers, which constitute the preferred object of the invention.

When one of the substituents R4a and R4b on the one hand and one of the substituents R5a and R5b on the other hand together form a methylenedioxy or ethylenedioxy radical, then both substituents, which form the methylene or ethylene radicals, are preferably present in the cis position. . Compounds to be highlighted are those of the formula I, in which in which R 1 signifies C 1-4 alkyl, R 2 means C 1-4 alkyl or hydroxy C 1-4 alkyl, R 3 signifies hydrogen, one of the substituents R 4a and R 4b signifies hydrogen , and the other means hydrogen, hydroxy or C1-4 alkoxy, or in which R4a and R4b together represent O (oxygen), one of the substituents R5a and R5b means hydrogen and the other means hydrogen, hydroxy, C1-4 alkoxy, or wherein R5a and R5b together represent O (oxygen), wherein R4a, R4b, R5a and R5b do not simultaneously have the meaning of hydrogen, R6 signifies hydrogen, halogen or trifluoromethyl, and R7 signifies hydrogen or halogen and their salts. One embodiment to be emphasized of the invention are compounds of the formula I * wherein -JO R 1 means C 1-4 alkyl, R 2 means C 1-4 alkyl or hydroxyC 1-4 alkyl, R 3 signifies hydrogen, one of the substituents R 4a and R 4b signifies hydrogen and the other signifies hydrogen, hydroxy, C 1-7 alkoxy 4, -15 one of the substituents R5a and R5b means hydrogen and the other means hydrogen, hydroxy, C1-4 alkoxy, in which R4a, R4b, R5a and R5b do not simultaneously have the meaning of hydrogen, R6 means hydrogen, halogen or trifluoromethyl, and R7 means hydrogen or halogen and their salts. An embodiment to be particularly emphasized of the invention are compounds of formula I *, in which R 1 means C 1-4 alkyl, R 2 means C 1-4 alkyl or hydroxymethyl, R 3 signifies hydrogen, R 4a signifies hydrogen, R 4b signifies hydroxy or C 1 alkoxy -4, R5a means hydrogen, hydroxy or C1-4 alkoxy, R5b signifies hydrogen, R6 signifies hydrogen, halogen or trifluoromethyl and R7 signifies hydrogen or halogen and its salts. A preferred embodiment of the invention are compounds of the formula I *, in which R1 means C1-4 alkyl, R2 means C1-4 alkyl, R3 signifies hydrogen, R4a signifies hydrogen, R4b signifies hydroxy, R5a signifies hydroxy, R5b signifies hydrogen , R6 signifies hydrogen, halogen or trifluoromethyl and R7 signifies hydrogen or halogen and their salts. The following illustrative compounds corresponding to the invention are specifically mentioned in the following Table 1 (Tab.1) based on the general formula I * by the meanings of the substituents and by the indicated positions of the substituents R3, R6 and R7: Tab . 1 R1 R2 R3 R4a R4b R5a R5b R6 R7 CH3 CH3 H O H H H H CH3 CH3 H H OH H H H H CH3 CH3 H O H H 2-Cl H CH3 CH3 H OH OH H 2 Cl H CH3 CH3 H O H H 2-Cl 6-Cl CH3 CH3 H OH OH H 2 Cl 6-Cl CH3 CH3 H H OCH3 H H H H CH3 CH3 H H OC2H5 H H H H CH3 CH3 H O H H 2-CFa H CH3 CH3 H OH OH H 2 CF3 H CH3 CH3 H O OH H H H CH3 CH3 H OH OH OH H H H CH3 CH3 6-Br or H H H H CH3 CH3 6-Br H OH H H H H CH3 CH3 6-Cl H OH H H H H CH3 CH3 6-Cl H OH OH H H H CH3 CH3 H OH OH OH H 2 -Cl H CH3 CH3 H OH OH OH 2 Cl 6-Cl CH3 CH3 H OH OH OH H 4-CI H CH3 CH3 H OH OH OH H 2-CFa H CH3 CH3 H OH OH OH 2 NHCO-OCH3 6-CH3 CH3 CH3 H OH OH OH 2-NHCO-OC2H4-OCH3 6-CH3 CH3 CH2OH H O H H H H CH3 CH2OH H OH H H H H Tab. 1, continued R1 R2 R3 R4a R4b R5a R5b R6 R7 CH3 CH2OH H O H H 2 -Cl H CH3 CH2OH H OH OH H 2 Cl H CH3 CH2OH H 0 H H 2 Cl 6-Cl CH3 CH2OH H OH OH H 2 Cl 6-Cl CH3 CH2OH H H O O H H H H H CH3 CH2OH H H OC2H5 H H H H CH3 CH2OH H H H 2-CF3 H CH3 CH2OH H OH OH H 2 CF3 H CH3 CH2OH H O OH H H H CH3 CH2OH H OH OH OH H H H CH3 CH2OH 6-Br 0 H H H H CH3 CH2OH 6-Br H OH H H H H CH3 CH2OH 6-Cl H O OH H H H H CH3 CH2OH 6-Cl H OH OH H H H CH3 CH2OH H OH OH OH 2 Cl H CH3 CH2OH H OH OH OH 2 Cl 6-Cl CH3 CH2OH H OH OH OH H 4-CI H CH3 CH2OH H OH OH OH 2-CF3 H CH3 CH2OH H OH OH OH 2 NHCO-OCH3 6-CH3 CH3 CH2OH H OH OH OH 2-NHCO-OC2H4-OCH3 6-CH3 as well as the salts of the compounds mentioned in Table 1, where the character "0" (oxygen) between R 4a and R 5b in Table 1 means a 7-oxo compound. The compounds according to the invention can be prepared as described by way of illustration in the following examples, or by the application of analogous process steps from the corresponding starting compounds. The starting compounds are known or can be prepared analogously to the known compounds. Depending on the substitution pattern in positions 7 and 8 (R4a / R4b or R5a / R5b), the compounds according to the invention can be prepared starting from 8-amino-imidazo [1,2-ajpyridines protected in N, known or capable of prepared in a known manner (see, eg, EP-A-0 229 470, or Kaminski et al., J. Med. Chem. 1985, 28, 876-892), according to the reaction schemes following: Scheme 1: The N-protected 8-amino-imidazo [1, 2-a] pyridine (Piv means here, as in the following schemes, a conventional protecting group, preferably the pivaloyl group), deprotonated in position 7. is reacted with aldehyde cinnamic The addition product is first oxidized (eg with manganese dioxide) and then epoxidized (eg with hydrogen peroxide). Under strongly basic conditions and then strongly acidic, dissociation of the protective group and ring closure is carried out. The subsequent reduction, if desired, of the keto group can be carried out, for example, with sodium borohydride. Scheme 2: Instead of the epoxidation according to scheme 1, the protective group is dissociated and the ring is closed under strongly acidic conditions. The subsequent reduction to alcohol, if desired, is carried out by means of sodium borohydride.

Scheme 3: The above scheme represents in an illustrative way an enantioseiectiva synthesis, in which it starts from the same imidazo [1,2-a] pyridines protected in N as in scheme 1. The reaction of these imidazo [1,2-ajpyridines in The deprotonised form with enantiomerically pure dioxolanes leads in the first place to a condensation product which can be cyclized under strongly acidic conditions with dissociation of the protecting groups. The subsequent reduction of the keto group with sodium borohydride (see also scheme 1) leads to the indicated end product with an enantiomeric purity greater than 90%.

Scheme 4: Starting from the aforementioned 8-amino-imidazo [1, 2-a] pyridines, the compounds substituted at the amino group of the 8-position by alkylation are obtained with alkylating agents bearing appropriate substituents (eg, R8a = hydrogen, R8b = halogen), or by reductive alkylations with correspondingly substituted ketones [R8a and R8b together represent O (oxygen)] with the aid of reducing agents such as sodium cyanoborohydride and these are subjected to ring closure by acid or basic catalysis to give the cyclic ketones, which can themselves be transformed by appropriate chemical transformations (see, eg, schemes 1 and 2) into the desired target compounds. If necessary, the C02R group can be reduced first before the cyclization (aldehyde stage), then hydroxy-substituted derivatives are formed in the 7-position which, in turn, can be converted by oxidation / reduction to the appropriate target compounds.

Scheme 5: In a variant of the process shown above in Scheme 4 where R5a and R8a = H (hydrogen) and R5b and R8b = together O (oxygen), the 8-amino-imidazo [1,2-a] pyridine is reacted firstly with ester derivatives of epoxycinnamic acid producing the regioselective opening of the epoxide (A). The products are cyclized under basic aprotic conditions (C). Alternatively, a saponification can be carried out and the free carboxylic acid derivative can be cyclized under acidic conditions (D). In both cases, the keto group can subsequently be reduced to alcohol, as represented in scheme 1, for example with sodium borohydride (g). In case the 8-amino-imidazo [1,2-a] pyridine is reacted with protected epoxycinnamic aldehyde derivatives (B), the products are allowed to close cyclically after dissociation of the acetal protecting group (F). ). Also, a reduction of the ester function to give the aldehyde and an acid cyclization (E) is possible. Not only the reduction of the keto function, but also the closure of the ring in the aldehyde stage, can be conducted enantioselectively, so that by using the corresponding enantiomerically pure epoxiderivatives an enantioselective synthesis is possible.

Scheme 6: Pr = protective group Lg = starting group Y = H, OR, NR2, halogen, etc.

In a further variant of scheme 4, an enantioselective synthesis is previously shown. The dihydroxycinnamic acid derivative is activated in the benzylic position, either directly or after the introduction of a protecting group into the second hydroxy group. The products thus obtained are reacted with the 8-amine-imidazo [1,2-a] pyridine. The closure of the ring is then carried out, eg under basic conditions. The subsequent step (reduction), if desired, is carried out analogously to scheme 3.

Scheme 7: The 8-halo-imidazo [1, 2-a] pyridines (X = halogen) are reacted with suitably substituted β-phenyl-β-amino acids under heavy metal catalysis (preferably Pd) to give the substituted amines, which are cyclized in turn according to the scheme 4. Instead of the COOR groups, aldehyde groups, if desired in the form of acetal, can also be incorporated (as already mentioned in scheme 4). Y represents H (hydrogen) or a dissociative protecting group before or after ring closure.

Scheme 8: Starting from the known imidazole or which can be prepared analogously, the closure of the resulting ring (optionally with protection of the hydroxy group) is favored by the presence of an enamine structure (equilibrium!). After the incorporation of the double denouement by oxidation, the reduction of the keto group to give the alcohol can be carried out as shown in scheme 1.

In the above schemes, "R" represents C1-4 alkyl. In the exemplified ester groups (-COOR or -C02R) it can be treated, instead of the radical -OR, of the other starting group, or instead of the ester it can be the other group, which by its functionality can be used analogously to the same. The compounds of the formula I, in which R 4a / R 4b or R 5a / R 5b mean C 1-4 alkoxy, C 1-4 alkoxy-C 1-4 alkoxy or C 1-4 alkylcarbonyloxy, can be prepared by conventional derivatization steps, such as those deserving the confidence of the experts (eg by alkylation or acylation) from the respective compounds in which R4a / R4b or R5a / R5b have the meaning of hydroxy. The compounds of the formula I, in which R 2 represents C 1-4 hydroxyalkyl, or the respective starting compounds of the schemes 1 to 8 can be prepared in a known manner from the corresponding esters or aldehydes by reduction, for example with sodium borohydride. sodium or lithium aluminum hydride (see, e.g., WO 94/18199). If desired, the reduction to give the hydroxy-C 1-4 alkyl group can be carried out to give the hydroxy-C 1-4 alkyl group can be carried out simultaneously with the reduction of the keto group in the 8-position and especially in the 7-position (R 4a and R4b represent together O). The isolation and purification of the substances according to the invention are carried out in a manner known per se, for example in such a way that the solvent is distilled off in vacuo and the residue obtained is recrystallized from an appropriate solvent, or it is subjected to one of conventional purification methods, such as, for example, column chromatography on an appropriate support material. The salts are obtained by redissolving the free compound in an appropriate solvent, for example in a chlorinated hydrocarbon, such as methylene chloride or chloroform, or a low molecular weight aliphatic alcohol (ethanol, isopropanol), containing the desired acid , or to which the desired acid is subsequently added. The salts are obtained by filtration, reprecipitation, precipitation with a non-solvent substance from the addition salt, or by evaporation of the solvent. The salts obtained can be transformed by alkalization or by acidification into the free compounds which can be transformed back into salts. In this way, non-pharmacologically compatible salts can be converted into pharmacologically compatible salts. The pure enantiomers, particularly the pure enatomers of the formula I *, which are the preferred object of the invention, can be obtained in any way that deserves the confidence of the experts, for example by enantioselective synthesis (see, eg, scheme 4) , by chromatographic fractionation in chiral separation columns, by derivatization with chiral auxiliary reagents, subsequent separation of the diastereoisomers, and dissociation of the chiral auxiliary group, by salt formation with acid acids, subsequent removal of the salts and release of the desired compound from of the salt, or by crystallization (fractionated) from a suitable solvent. Additional object of the invention are the processes described in the above schemes, as well as the intermediate products of the processes, particularly those intermediate products of the processes of schemes 1, 2, 3, 4, 5, 6, and 7, which can be isolate before the cyclization step. Subsequent examples serve for further illustration of the invention without limiting the same. Also, additional compounds of the formula I, the preparation of which is not explicitly described, can be prepared analogously, or in any manner that deserves the confidence of the experts, with the use of conventional process techniques. The abbreviation min. represents minute (s), h represents hour (s) and ee "enantiomeric excess" (from English "enantiomeric excess"). Examples Final Products 1. 2,3-Dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazoM, 2-h1f1,71 naphthyridin-7-one A solution of 4.5 g of 2,3-dimethyl -7- (3-phenyl-1-oxo-2-propenyl) -8-pivaloylamino-imidazo [1,2-ajpyridine in 30 ml of dioxane is mixed with 20 ml of concentrated hydrochloric acid, refluxed for 8 h, adjust to pH 7.0 under cooling with 2 N caustic soda, and extract three times with 50 ml of ethyl acetate. The combined extracts are washed with water, dried over potassium carbonate and concentrated in vacuo to dryness. The remaining viscous oil is chromatographed on silica gel with ethyl acetate / petroleum ether (1: 1) over eluent. 2.6 g of the title compound with a melting point of 138-40 ° C are obtained. 2. 9- (2-Chlorophenyl) -2,3-dimethyl-7,8,9,10-tetrahydro-imidazori, 2-hl f 1, 71 naphthyridine-7-one The title compound with melting point 80-2 ° C is obtained with a yield of 73% analogously to Example 1, from 7- [3- (2-chlorophenyl) -1-oxo-2-propenyl] -8-pivaloylamino-2,3-dimethyl-imidazo [1,2-a] ] pyridine. 3. 9- (2,6-dichloro-phenyl) -2,3-dimethyl-7,8,9,10-tetrahydro-imid azori, 2-hl-ri, 71-naphthyridine-7-one The title compound with melting point 248-9 ° C, 41% yield is obtained analogously to Example 1, starting from 7- [3- (2-dichlorophenyl) -1-oxo-2-propenyl] -8-pivanedylamino-2 , 3-dimethyl-imidazo [1,2-a] pyridine. 4. 9- (2-Trifluoromethylphenyl) -2,3-d, methyl-7,8,9,10-tetrahydro-midazo f1.2-h] f1.71naphthyridine-7-one The title compound with point of Fusion 184-5 ° C, is obtained in 41% yield analogously to Example 1, starting from 7- [3- (2-trifluoromethylphenyl) -1-oxo-2-propenyl] -8-pivalo -lamine- 2,3-dimethyl-imidazo [1,2-ajpyridine. 5. 7-Hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-terahydro-imydazoM, 2-h1 [1.71 naphthyridine A suspension of 1 g of 2,3-dimethyl-9-phenyl-7, 8,9, 10-tetrahydro-imidazo [1,2-h] [1,7] naphthyridin-7-one in 15 ml of methanol is mixed with small portions with 450 mg of sodium borohydride at room temperature. The yellowish solution obtained is stirred for 2 h and then diluted with water and ice. The precipitate produced is filtered off with suction and washed with a little cold 2-propanol. 800 mg of the title compound with melting point 210-12 ° C are obtained. 6. 9 - (2-CI or rof en il) -7-hydroxy-2,3-dimethyl-7,8,9,10-tetrahydro-imidazof1,2-rt1f1,7lnaphthyridine-7-one The title compound , with melting point 150-2 ° C, is obtained with a yield of 73% analogously to example 5, from 9- (2-chlorophenyl) -2,3-dimethyl-7, 8,9,10-tetrahydro-imidazo [1, 2-h] [1, 7] naphthyridin-7-one. 7. 9- (2,6-Dichlorophenyl) -7-hydroxy-2,3-dimethyl-7,8,9,10-tetrahydro-imidazof1,2-hlf1,71naphthyridine The title compound with the melting point 155 -7 ° C, is obtained with a yield of 72% analogously to example 5, from 9- (2,6-dichlorophenyl) -2,3-dimethyl-7,8,9,10-tetrahydro-imidazo [1, 2-h] - [1,7] naphthyridin-7-one. 8. 9- (2-Trifluoromethylphenyl) -7-hydroxy-2,3-dimethyl-7.8.9.10-tetrahydro-imidazofl, 2-hU1, 71-naphthyridine The title compound with melting point 145-7 ° C, obtained in a yield of 72% analogously to Example 5, starting from 9- (2-trifluoromethylphenyl) -2,3-dimethyl-7,8,9,10-tetrahydro-imidazo [1,2-h] [1 , 7] naphthyridin-7-one. 9- 8-Hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazo f1,2-hU1,71naphthyridine-7-one A solution of 500 mg of 2,3-dimethyl-7- (2,3-epoxy-1-oxo-3-phenylpropyl) -8-pivalylamino-imidazole [1,2-a] pyridine in 5 ml of dry ethanol is mixed, under vigorous stirring, with 95 mg of hydroxide lithium and, after two hours of stirring at room temperature, it is cooled in the ice bath at 0 ° C. The precipitated crystals are filtered with suction and washed with a little cold ethanol. After drying under high vacuum, the solids are incorporated in 5 ml of 90% sulfuric acid at room temperature, and stirred for 1 h. After that, it is neutralized, under cooling with ice, with 40% caustic soda cooled. The precipitates produced in this way are separated by filtration and dried under vacuum. 145 mg of the title compound are obtained with melting point 232-4 ° C. 10. 7,8-Dihydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazori.2-h1f1,71naphthyridine 700 mg of 8-hydroxy-2,3-dimethyl-9- phenyl-7,8,9, 10-tetrahydro-imidazo [1, 2-h] [1,7] naphthyridin-7-one are suspended in 15 ml of methanol and mixed with stirring at room temperature with stirring. 200 mg of sodium borohydride. After two hours of stirring, the whole is poured into 100 ml of ice water. The precipitate is produced, separated by filtration, briefly dried in vacuo and recrystallized from a little 2-propanol. 500 mg of the title compound with melting point 150-2 ° C are obtained. 11. (8R, 9R) -2,3-Dimet il-8-Hydro xi-9 -fe nil-7, 8,9,10-tetrahydroimidazo M, 2-hlfl, 71naphthyridin-7-one 10.8 g (24 mmol) of 2,3-dimethyl-7 - [(2S, 3R) -2,3-0-isopropylidene-phenol- (3) -propanon- (1) -yl- (1)] - 8-pivaloylamino Imidazo [1, 2-a] pyridine (ee> 95%, Daicel Chiralcel HPLC) are incorporated in 50 ml of 70% sulfuric acid under ice cooling for 4 min. In this way a suspension is formed, which is converted after 30 min into an orange solution. After the addition is complete, the ice bath is removed and further stirred at room temperature. After 50 h, the reaction solution is introduced into ice water and dichloromethane is added, and then it is adjusted to pH 8 with 6N caustic soda and saturated sodium hydrogencarbonate solution. The organic phase is separated. The aqueous phase is extracted twice with dichloromethane. The organic phases are combined and washed with a little distilled water. It is then dried over anhydrous sodium sulfate, filtered and concentrated on a rotary vacuum evaporator. The concentrated residue is subjected to chromatography on silica gel (móvikdichloromethane / methanol phase, 100/1). The main fraction is concentrated and mixed with ethyl acetate, whereby the title compound crystallizes as a yellow solid. This precipitate is filtered with suction and dried in the vacuum drying cabinet at 50 ° C until constant weight. 4.22 g (57%, ee > 95% HPLC Daicel Chiralcel) of the fusion title compound are obtained: 231-4 ° C. 12. (7R. 8R. 9R) -2.3-Dimethyl-7,8-dihydroxy-9-phenyl-7.8,9,10-tetrahydro-midazo [1,2-h1f1,71 naphthyridine 6 g (19.52. millimoles) of (8R, 9R) -2,3-dimethyl-8-hydroxy-9-phenyl-7,8,9,10-tetrahydro-imidazo [1,2-h] - [1,7] naphthyridin-7 -one (ee: > 90% HPLC Daicel Chiralcel) are suspended in 60 ml of ethanol and cooled in the methanol-ice bath at -5 ° C to 0 ° C. At this temperature, sodium borohydride (0.81 g, 21.47 millimoles) is added during 0.5 h by means of a spatula (gas evolution). After the complete addition, it is stirred for a further 10 min and then concentrated in the rotary vacuum evaporator at a bath temperature of 40 ° C. The oily residue obtained is collected in distilled water and extracted three times with chloroform. The organic phases are combined and washed with a little water, then dried with anhydrous sodium sulfate and filtered. The filtrate is concentrated in the rotary vacuum evaporator and is evaporated together with the ketone, whereby the title compound crystallizes. The precipitate is filtered, washed with acetone and dried in the vacuum drying cabinet at 50 ° C until constant weight. 5.15 g (85.3%, ee >) are obtained90%, HPLC Daicel Chiralcel) of the title compound as colorless crystals of melting point: 206-9 ° C. 13. (7S.8R.9R) -2.3-Dimethyl-7.8-dihydroxy-9-phenyl-7.8.9.10-tetrahydro-imidazQf1,2-h1f1.7lnaphthyridine 2 g of the mother liquor of example 12 are chromatographed on silica gel (mobile phase: ethyl acetate / methanol, 19/1) and give 0.35 g of the title compound with an oil, which crystallizes after the addition of ethyl acetate. Melting point: 199-200 ° C (ethyl acetate). 14. (8R.9R) -3-Formyl-8-hydroxy-2-methyl-7-oxo-9-phenyl-7.8.9.10-tetrahydro-imidazoic1.2-hlf1.7lnaphthyridine 1 g of (8R , 9R) -8-hydroxy-2,3-dimethyl-7-oxo-9-phenyl-7,8,9,10-tetrahydro-imidazo [1, 2-h] [1,7] naphthyridine is dissolved in 20 ml of dry chloroform, and 5 g of potassium permanganate are added. After stirring the reaction mixture for 40 days at room temperature, the solids are filtered off. The filtrate is chromatographed twice on silica gel (mobile phase: dichloromethane / methanol, 13/1) and gives 0.07 g of the title compound as a semi-solid material. 15. (7R, 8R, 9R) -3-Hydroxymethyl-7,8-dihydroxy-2-methyl-9-pheny1-7,8,9,10-tetrahydro-imidazoM, 2-hlf-1, 71-naphthyridine-7 -one 0.07g of (8R, 9R) -3-formyl-8-hydroxy-2-methyl-7-oxo-9-phenyl-7,8,9, 10-tetrahydro-imidazo [1, 2-h] [ 1, 7] naphthyridine are dissolved in 5 ml of dry methanol, and 0.1 g of sodium borohydride is added. The mixture is stirred for 30 min and concentrated in vacuo. The oily residue is partitioned between water and chloroform. The organic phase is separated, dried over anhydrous sodium sulfate and concentrated. The product is purified by flash chromatography on silica gel (mobile phase: dichloromethane / methane, 9/1) and provides 0.05 g of the title compound as a semi-solid material. 1H-NMR (proton nuclear magnetic resonance, from the German nuklear rnagnetishce Resonanz) (CD30H, 400 MHz) d = 1.90 (s, 3H, 2-CH3), 3.87 (dd, J 8.9 = 9.5 Hz , J 8.7 = 8, 0 Hz, 1H, 8-H), 4.45 (d, J 9, 8 = 9, 4 Hz, 1H, 9-H), 4.59 (bs, 2H, 3-CH2 ), 5.42 (d, J 7.8 = 8.0 Hz, 1H, 7-H), 7.03 (d, J 6.5 = 6.9 Hz, 1H, 6H), 7.35-7, 42 (m, 3H, 9-Ph), 7.55 (d, J = 7.0 Hz, 2H, 9Ph), 7.77 (d, J5.6 = 7.0 Hz, 1H, 5-H ). 6. (7S-8R, 9R) -7,8-lsopropylidenedioxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazoi 1,2-hlfl 1,7lnaphthyridine 0.3 g of (7S, 8R, 9R ) -2,3-dimethyl-7,8-dihydroxy-9-phenyl-7,8,9, 10-tetrahydro-imidazo [1,2-h] [1,7] naphthyridine are dissolved in 5 ml of dry acetone and 10 ml of dry N, N-dimethylformamide. 2,2-Dimethoxypropane (20 ml) and p-toluenesulfonic acid monohydrate (0.68 g) are added, and the mixture is stirred for 20 h at room temperature. The reaction mixture is partitioned between water and dichloromethane. The organic phase is separated, washed with water and dried over anhydrous sodium sulfate. After evaporation of the solvent, the residue is chromatographed on silica gel (ethyl acetate / methanol phase, 20/1) and gives 0.2 g of the title compound as colorless needles. Melting point: 231-232 ° C (decomposition, diethyl ether): Starting compounds A. 2,3-Dimethyl-7- (3-phenyl-1-oxo-2-propenyl) -8-pivaloyl-amino-imidazof1 , 2-a] pyridine Method A a) 7-Tributylstannyl-2,3-dimethyl-8-pivaloylamino-imidazo [1,2-a] pyridine A solution of 1 g of 2,3-dimethyl-8-pivaloylamino-imidazo [1,2-ajpyridine in 50 ml of diethyl ether is mixed at -78 ° C dropwise with 8 ml of a 1.5 molar solution of te rc-buti I-lithium in n-pentane. The mixture is stirred 15 min and then mixed with 3.3 ml of tri-n-butyltin chloride. After that the internal temperature is allowed to rise to room temperature, poured into ice water, extracted three times with ethyl acetate, washed with combined extracts with a little water, dried over potassium carbonate, the solvent is removed in vacuo and the oil obtained is chromatographed on silica gel with ethyl acetate / petroleum ether (1: 3) as eluent. 1.3 g of 7-tributylstannil-1 are obtained, 3-dimethyl-8-pivaloylamino-imidazo [1,2-a] pyridine as a viscous oil. b) 2,3-Dimethyl-7- (3-phenyl-1 -oxo-2-propenyl) -8-pivaloylamino-imidazo [1, 2-a] pyridine A solution of 1 g of 7-tributylstannil-1, 3 dimethyl-8-pivaloylamino-imidazo [1,2-a] pyridine in 15 ml of terahydrofuran is mixed successively with 85 mg of lithium chloride, 60 mg of bis-8-acetonitrile) -palladium chloride (ll) and 340 mg of cinnamic acid chloride. The mixture is stirred for 3 h at 60 ° C. The yellowish precipitate is filtered with suction after cooling to 0 ° C and washed with a little tetrahydrofuran and diethyl ether. After drying under vacuum, 702 mg of the title compound are obtained as hydrochloride salt of melting point 263-5 ° C (with decomposition). Method B a) 2,3-Dimethyl-7- (3-phenyl-1-hydroxy-2-propenyl) -8-pivaloylamino-imidazo [1,2-a] pyridine A strongly stirred solution of 41 g of 8- p-vallamino-2,3-dimethyl-imidazo [1,2-a] pyridine is mixed at -78 ° C in an argon protective atmosphere with 320 ml of a 1.5 molar solution available for sale from Buti-I tio in n-pentane, drop by drop, in such a way that the temperature does not exceed -70 ° C. After a further 15 minutes of stirring at -78 ° C, a solution of 61 g of cinnamic aldehyde in 50 ml of dry diethyl ether (internal temperature <) is added dropwise.; -68 ° C). The mixture is then allowed to warm to room temperature, carefully poured into ice-water, extracted three times with a total of 500 ml of ethyl acetate, the reddish organic phase is washed with distilled water, dried over sodium sulfate, sodium and the solvent is removed in vacuo. The remaining yellowish suspension is mixed with diethyl ether. The crystals that are produced are filtered with suction. 30 g of 2,3-dimethyl-7- (3-phenyl-1-hydroxy-2-propenyl) -8-pivaloylamino-imidazo [1,2-a] pyridine with melting point 194-5 ° C are obtained. b) 2,3-Dimethyl-7- (3-phenyl-1-oxo-2-propenyl) -8-pivaloylamino-imidazo [1, 2-ajpyridine A solution of 35.5 g of 2,3-dimethyl-7- (3-phenyl-1-hydroxy-2-propenyl) -8-pivaloylamino-imidazo [1,2-a] pyridine in 900 ml of trichloromethane is mixed with 60 g of manganese dioxide and stirred vigorously for 20 h at room temperature. It is then filtered, the filtrate is concentrated in vacuo to dryness, and the oil obtained is mixed with a small amount of diisopropyl ether, the crystals obtained in this way are filtered with suction. 31.5 g of the title compound with melting point 108-10 ° C are obtained. B. 7-f3- (2-Chlorophenyl) -1-oxo-2-propenyp-8-pivaloylamino-2,3-dimethyl-imidazoic 1,2-a] pyridine The title compound, with melting point 158-60 ° C, is obtained in 42% yield in the form of hydrochloride, analogously to Example A, Method A, by corresponding transformation with 2-chlorocinnamic acid chloride. C. 7-f3- (2,6-Dichlorophenyl) -1-oxo-2-propenyl-8-pivaloylamino-2,3-dimethyl-imidazole, 2-alpyridine The title compound, with melting point 218-19 ° C, is obtained in 51% yield in the form of hydrochloride, analogously to Example A, Method A, by corresponding transformation with 2-6-dichlorocinnamic acid chloride. D. 7- [3- (2-6-Tri-fluoro-methyl-n-nyl) -1-oxo-2-p-penyl-8-pivaloylamino-2,3-dimethyl-im-dazof-1,2-pyridine The compound of title, with melting point 206-8 ° C, is obtained in a 12% yield in the form of a hydrochloride, analogously to Example A, Method A, by corresponding transformation with 2-trifluoromethyl cinnamic acid chloride. E. 2,3-Dimethyl-7- (2,3-epoxy-1-oxo-3-phenylpropyl) -8-pivaloylamino-imidazof1,2-alpyridine A mixture of 4 g of 2,3-dimethyl-7- ( 3-phenyl-1-oxo-2-propenyl) -8-pivaloylamino-imidazo [1,2-a] pyridine in 60 ml of acetone and 400 mg of sodium hydroxide in 12 ml of water is mixed dropwise with stirring intense at 30 ° C with 5.6 ml of 30% aqueous hydrogen peroxide, available for sale (20 min.). After further stirring for 30 minutes at 30 ° C, it is cooled to 0 ° C and mixed with a mixture of 60 ml of water, 13 g of sodium thiosulfate and 30 ml of ethyl acetate. After phase separation, the aqueous phase is extracted with 20 ml of ethyl acetate. The organic phases are combined, washed with a small amount of water and dried over potassium carbonate. After removal of the solvent in vacuo, the remaining oil is dried under high vacuum. 4 g of the title compound are obtained as an amorphous mass. F. 2,3-Dimethyl-7-f (2S.3R) -2,3-Q-isopropylidene-phenyl- (3) -propanone- (1) -yl- (1) 1-8-pivaloylamino- Mixton, 2-a1pyridine 60 g (0.245 mole) of 2,3-dimetii-8-pivaloylamino-imidazo [1,2-ajpyridine dissolve in the absence of moisture and in an argon atmosphere in 1.5 liters of ether anhydrous diethyl ether, and cooled to -75 ° C, by means of a flex-needle, 408 ml (0.612 mole) of tert-butyllithium solution (1.5 M in n-pentane) are introduced drop by drop, such that the temperature does not exceed -65 ° C (30 min.). A red suspension forms. After complete addition, the suspension is stirred at -75 ° C for an additional 30 min. It is then poured slowly dropwise over 30 in 1/3 of a solution consisting of 145 g of (2S, 3R) -2,3-0-isopropylidene-phenyl- (3) -propionic acid methyl ether (ee: 99.05 %, HPLC Daicel Chiralcel) in 150 ml of absolute THF at a temperature below -65 ° C. The remaining quantity is then added dropwise (5 min.), Resulting in a rise in temperature to -60 ° C. Once the addition is complete, the cooling bath is removed. When an internal temperature of -30 ° C is reached, 20 ml of mental are added, and at an internal temperature of 0 ° C 200 ml of distilled water are added. The aqueous phase is separated in the separating funnel, and the organic phase is washed five times with 100 ml of distilled water each time, after which the organic phase is extracted three times with 10% sulfuric acid (200 ml, 50 ml). ml, 50 ml). Sulfuric acid phases come together, they are mixed with 200 ml of dichloromethane and adjusted to pH 2.3 with 10 N caustic soda under cooling with ice and vigorous stirring. The organic phase is separated. The aqueous phase is extracted with 30 ml of dichloromethane. The combined dichloromethane phases are washed twice with a small amount of distilled water. It is then dried over anhydrous sodium sulfate and the solvent is completely removed in vacuo. A brown oil is obtained, which is mixed with 50 ml of diethyl ether. After the inoculation, crystals are formed which, after overnight maintenance, are separated by filtration and washed with diethyl ether. After drying under vacuum, 57.7 g (52.5%, ee >) are obtained; 99%, HPLC Daicel Chiralcel) of the title compound as a light yellow powder of melting point 76-80 ° C. Technical Applicability The compounds of the formula I and their salts possess valuable pharmacological properties, which make them technically usable. Said compounds exhibit particularly adequate inhibition of gastric acid secretion and an excellent effect of protecting the stomach and intestine in homeothermic animals, particularly in humans. At the same time, the compounds according to the invention are characterized by a high selectivity of action, an advantageous duration of action, a particularly satisfactory enteral activity, the absence of essential side effects and a large therapeutic range. Under "protection of the stomach and intestine" is meant in this context the prevention and treatment of gastrointestinal diseases, particularly diseases and inflammatory gastrointestinal lesions (such as Ulcus ventriculi, Ulcus duodeni, gastritis, irritation of the stomach caused by hyperacidity or medicaments), which can be caused for example by microorganisms (eg Helicobacter pylori), bacterial toxins. medications (eg certain antiphlogistic and antirheumatic drugs), chemicals (eg ethanol), gastric acid, or stress situations. The compounds according to the invention are tested, with regard to their outstanding properties, according to different models, in which the anti-ulcerogenic and anti-secretory properties are determined, which surprisingly surpass with clarity those of the known compounds of the prior art. Due to these properties, the compounds of the formula I and their pharmacologically compatible salts are very suitable for use in human and veterinary medicine, being used in particular for the treatment and / or prophylaxis of diseases of the stomach and / or intestine. A further object of the invention are, therefore, the corresponding compounds of the invention for application in the treatment and / or prophylaxis of the diseases mentioned above. Likewise, the invention encompasses the application of the compounds corresponding to the invention for the preparation of medicaments, which they use for the treatment and / or prophylaxis of the diseases mentioned above. Additionally, the invention encompasses the application of the compounds corresponding to the invention for the treatment and / or prophylaxis of the diseases mentioned above.

A further object of the invention are medicaments containing one or more compounds of the formula I and / or their pharmacologically compatible salts. The medicines will be prepared according to processes known per se, common to experts. As medicaments, the pharmacologically active compounds corresponding to the invention (= active materials) are used as such, or preferably in combination with pharmaceutically suitable adjuvants or vehicles in the form of tablets, dragees, capsules, suppositories, patches (eg as TTS). ), emulsions, suspensions or solutions, in which the content of active material is advantageously comprised between 0.1 and 95% and in which by the respective choice of the adjuvant materials and vehicles a form of galenic presentation can be achieved exactly adjusted to the material active and / or the desired action input (eg a delayed form or a gastric juice resistant form). Which adjuvant materials and vehicles are suitable for the desired drug formulations is a usual matter for the experts due to their experience. In addition to solvents, gel formers, suppository bases, adjuvant materials for tablets and other vehicles of the active material, for example antioxidants, dispersing agents, emulsifiers, antifoams, flavor correctors, preserving agents, solution agents, dyeing agents may be used. permeation promoters and complex formers (eg cyclodextrins). The active materials can be applied orally, parenterally or percutaneously. Generally, in human medicine it has been advantageous to administer ei or the active agents in the case of oral intake in a daily dose of about 0.01 to about 20, preferably 0.05 to 5, and especially 0.1 to 1, 5 mg / kg. of body weight, optionally in the form of several, preferably from 1 to 4, simple doses for obtaining the desired results. In the case of a parenteral treatment, analogous dosages or (especially in the case of the intravenous administration of the active agents) can generally be used in lower dosages. The establishment of the optimal dosage required in each case and the application modality of the active materials can be easily determined by each expert by virtue of his experience. In case the compounds according to the invention and / or their salts are used for the treatment of the aforementioned diseases, the pharmaceutical preparations can also contain one or more pharmacologically active components of other drug groups. For example, there can be mentioned tranquilizers (for example from the group of benzodiazepines, eg Diazepam), spasmolytics (eg Bietamiverin or Camilofin), anticholinergics (eg Oxifenciclimin or Fencarbamid), local anesthetics (eg. Tetracaine or Propacaine), and optionally ferments, vitamins or amino acids. In this context, the combination of the compounds according to the invention with drugs, which inhibit the secretion of the acid, such as, for example, H2 blockers (eg Cimetidine, Renitidine), H + / K + -ATPase inhibitors (e.g. eg Omeprazole, Pantoprazole), or additionally with the so-called peripheral anticholinergics (eg Pirenzepine, Telenzepine) as well as with gastrin antagonists, in order to reinforce the main effect in the additive or superadditive sense and / or eliminate or reduce the side effects or additionally the combination with antibacterially active substances (such as, for example, cephalosporins, tetracyclines, penicillins, macrolides, nitroimidazoles or even bismuth salts) for the control of Helicobacter pylori. As a component of the combination with antibacterial activity, mention may be made, for example, of Mezclocillin, Ampicillin, Amoxicillin, Cefalotin, Cefoxitin., Cefotaximo, Imipenem, Gentamicin, Amikacin, Erythromycin, ciprofloxacin, metronidazole, Clarithromycin, Azithromycin and combinations thereof (eg clarithromycin + Metronidazole). Pharmacology The excellent gastric protective effect and the inhibitory effect of gastric acid secretion of the compounds corresponding to the invention can be demonstrated in tests carried out on experimental models in animals. The compounds corresponding to the invention tested in the models mentioned below have been identified with numbers corresponding to the numbers of these compounds in the examples. Testing the inhibitory effect of secretion in the perfused stomach of the rat In Table A below, the influence of the compounds corresponding to the invention is presented after intravenous administration on the secretion of pentagastrin-stimulated acid from the stomach of the rat. perfused in vivo. Table A Methodology After tracheotomy, the abdomen of narcotized rats (CD rats, females 200-250 g, intramuscular 1.5 g / kg urethane) was opened by a medium epigastric incision, and a transoral PVC catheter was fixed in the esophagus. and another additional catheter via pyloric route, in such a way that the ends of the flexible probe penetrated just the lumen of the stomach. The catheter from the pylorus led out through a lateral opening in the right abdominal wall. After thorough washing (approximately 50-100 ml) a physiological solution of NaCl heated at 37 ° C (0.5 ml / min., PH 6.8-6.9, Braun-Unita I) was flowed continuously through the stomach. The eluent was collected in each case in a 15-minute interval, the pH value was determined (pH-Meter 632, glass electrode Ea 147, internal diameter = 5 mm, Metrohm) and, by titration with a 1.01 NaOH solution. Freshly prepared N until pH 7 (Dosimat 665 Metrohm), the secreted HCl was determined. Stimulation of gastric secretion was performed by prolonged infusion of 1 μg / kg. (= 1.65 ml / h) intravenous pentagastrin (left femoral vein) approximately 30 min. after the end of the operation (that is, after the determination of 2 previous fractions). The substances to be tested were administered intravenously in 1 ml volume of liquid / kg. 60 min after the start of the prolonged infusion of pentagastrin. The body temperature of the animals was maintained at a constant value of 37.8-38 ° C by means of infrared radiation and electric pillows (continuous automatic regulation by a rectal temperature sensor).

Claims (10)

CLAIMS 1. Compounds of formula I wherein R 1 signifies C 1-4 alkyl, R 2 means C 1-4 alkyl or hydroxy C 1-4 alkyl, R 3 signifies hydrogen or halogen, one of substituents R 4a and R 4b signifies hydrogen, and the other signifies hydrogen, hydroxy, C 1 alkoxy -4, C 1-4 alkoxy-C 1-4 alkoxy or C 1-4 alkylcarbonyloxy, or in which R 4a and R 4b together represent O (oxygen), one of the substituents R5a and R5b means hydrogen and the other means hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkoxy-alkoxy
1. C1-4 or C 1 -4 -carbonyloxy alkyl, or in which R 5a and R 5b together represent O (oxygen), or in which one of the substituents R 4a and R 4b on the one hand and one of the substituents R 5a and R 5b on the other hand in each case hydrogen and the other substituents in each case together form a methylenedioxy radical (-0-CH2-0-) or an ethylenedioxy radical (-0-CH2-CH2-O-), where R4a, R4b, R5a and R5b does not simultaneously have the meaning of hydrogen, R6 means hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy, alkoxy
2. C 1-4 -carbonylamino, C 1-4 alkoxy-C 1-4 alkoxycarbonylamino or trifluoromethyl and R 7 means hydrogen, halogen, C 1-4 alkyl or C 1-4 alkoxy, and their salts. 2. Compounds of the formula I, according to claim 1, wherein R1 represents C1-4 alkyl, R2 means C1-4 alkyl or hydroxyC1-4 alkyl, R3 means hydrogen, one of the substituents R4a and R4b means hydrogen, and the other means hydrogen, hydroxy or C 1-4 alkoxy, or in which R 4a and R 4b together represent O (oxygen), one of the substituents R 5a and R 5b signifies hydrogen and the other means hydrogen, hydroxy, C 1 alkoxy - 4, or in which R5a and R5b together represent O (oxygen), where R4a, R4b, R5a and R5b do not simultaneously have the meaning of hydrogen, R6 means hydrogen, halogen or trifluoromethyl, and R7 signifies hydrogen or halogen and its salts .
3. 3. Compounds according to claim 1, characterized by the formula I * wherein R 1 means C 1-4 alkyl, R 2 means C 1-4 alkyl or hydroxyC 1-4 alkyl, R 3 signifies hydrogen, one of the substituents R 4a and R 4b signifies hydrogen and the other signifies hydrogen, hydroxy, C 1-4 alkoxy, one of the substituents R5a and R5b signifies hydrogen and the other means hydrogen, hydroxy, C1-4 alkoxy, in which R4a, R4b, R5a and R5b do not simultaneously have the meaning of hydrogen, R6 signifies hydrogen, halogen or trifluoromethyl, and R7 means hydrogen or halogen and its salts.
4. 4. Compounds of the formula I * according to claim 3, wherein R1 means C1-4 alkyl, R2 means C1-4 alkyl or hydroxymethyl, R3 signifies hydrogen, R4a signifies hydrogen, R4b signifies hydroxy or C1-4 alkoxy R5a means hydrogen, hydroxy or C1-4 alkoxy, R5b signifies hydrogen, R6 signifies hydrogen, halogen or trifluoromethyl and R7 signifies hydrogen or halogen and their salts.
5. 5. Compounds of the formula I * according to claim 3, wherein R1 represents C1-4 alkyl, R2 means C1-4 alkyl, R3 signifies hydrogen, R4a signifies hydrogen, R4b signifies hydroxy. R5a means hydroxy, R5b signifies hydrogen, R6 signifies hydrogen, halogen or trifluoromethyl and R7 signifies hydrogen or halogen and their salts.
6. 6. Compounds according to claim 1, selected from the group consisting of 7,8-dihydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazolf1,2-h] [1, 7] naphthyridine, 2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazole [1, 2-h] [1,7] naphthyridin-7-one, 9- (Dichlorophenyl) -2 , 3-dimethyl-7,8,9,10-tetrahydro-imidazole [1, 2-h] [1,7] naphthyridin-7-one, 9- (2,6-dichlorophenyl) -2,3-dimethyl- 7,8,9,10-tetrahydro-imidazole [1, 2-h] [1,7] naphthyridin-7-one, 9- (2-trifluoromethylphenyl) -2,3-dimethyl-7,8,9,10 -tetrahydro-imidazole [1,2-h] [1,7] naphthyridin-7-one, 7-hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazole [ 1,2-h] [1,7] naphthyridine, 9- (2-chlorophenyl) -7-hydroxy-2,3-dimethyl-7,8,9,10-tetrahydro-imidazole [1,2-h] [ 1,7] naphthyridine, 9- (2,6-dichlorophenyl) -7-h idroxy-2,3-dimethyl-7,8,9,10-tetrahydro-midazole [1,2-h] [1,7] naft Ridin, 8-hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazole [1, 2-h] [1,7] naphthyridin-7-one, (7S, 8R, 9R) -2,3-dimethyl-7,8-dihiroxy-9-phenyl-7,8,9,10-tetrah-idro-imidazole [1,2-h] [1,7] naft indine, (8R, 9R ) -3-formyl-8-hydroxy-2-methyl-7-oxo-9-phenyl-7,8,9,10-tetrahydro-imidazole [1,2-h] [1,7] naphthyridine, (7R, 8R, 9R) -hydroxymethyl-7,8-dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydro-irnidazole [1,2-h] [1,7] naft indine, ( 7S, 8R, 9R) -7,8-isopropylidenedioxy-2,3-dimethyl-9-phenyl7,8,9,10-tetrahydro-imidazole [1,2-h] [1,7] naphthyridine, or one of its you go out.
7. 7. A compound according to claim 6, with 9R configuration, or one of its salts. A compound according to claim 1 with the chemical designation (7R, 8R, 9R) -7,8-dihydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydro-imidazole [ 1,2-h] [1,7] naphthyridine, or one of its salts. 9. Medicament containing a compound according to claim 1 and / or one of its pharmacologically compatible salts, together with conventional adjuvants and / or pharmaceutical vehicles. 10. Use of compound according to claim 1 and its pharmacologically compatible salts, for the preparation of drugs intended for the prevention and treatment of gastrointestinal diseases.