CYCLIC BENZIMIDAZOLES

Bi. 7-Hydroxy-6- (2-hydroxy-3-phenyl-propyl) 2-methyl-3- (2-trimethylsilany!-ethoxymethylr3lf benzimidazole-5-carboxylic Acid Dimethylamide A suspension of 0.7 g (1. 4 mml) 7-hydroxy-2-methyl-6- (3-oxo-3-phenyl-propyl)-3- (2-trimethylsilanyl- ethoxymethyl)-3Hbenzimidazole-5-carboxyiic acid dimethylamide in 20 mi ethanol was treated with 0.7 g (1.7 mmol) sodium borohydride and the reaction was stirred at room temperature for 1 h. A satured ammonium chloride solution was added and the reaction was stirred for further 30 min.. The reaction mixture was poured into water and extracted with dichloromethane (3 x 20 ml). The organic layers were dried over magnesium sulphate and concentrated in vacuo to afford 0.7 g (100%) of the title compound as a white foam.
BJ. 7-Hydroxy-2-methyl-6-(3-oxo-3-phenyl-propyl)-3-(2-trimethylsilanyl-ethoxymethyl)-3H- benzimidazole-5-carboxylic Acid Dimethylamide A solution of 2.6 g (7.3 mmol) 7-hydroxy-2-methyl-3- (2-trimethylsilanyl-ethoxymethyl)-3H-benzo-imi- dazole-5-carboxylic acid dimethylamide in 160 mi dichloromethane was treated with 1. 6 g (8.8 mmol) N, N-dimethylmethylenimmonium iodide and the reaction was stirred at room temperature for 2.5h. The solvent was removed in vacuo, the residue was suspended in 30 ml toluene and the suspension was treated with 0.90 g (5.7 mmol) acetophenone pyrrolidine enamine. After heating at 100° C for 3h, the reaction mixture was concentrated in vacuo. The residue was purified by column chromatography on silica gel (ethyl acetate/petroleum ether = 5:1) to afford 0. 71 g (20%) of the title compound as a beige solid, m. p. 192°-194°C.
BK. 7-Hydroxy-2-methyl-3- (2-trimethylsilanyl-ethoxymethyly-3N-benzimidazole-5-carboxylic Acid Dimethylamide A solution of 3.6 g (8.3 mmol) 7-benzyloxy-2-methyl-3- (2-trimethylsilanyl-ethoxymethyl)-3H-benzo-imi- dazole-5-carboxylic acid dimethylamide in 400 mi ethanol was hydrogenated over 365 rng 10% Pd/C at room temperature for 1 h. The catalyst was filtered off and the filtrate was concentrated in vacuo. The residue was crystallized from diisopropyl ether to afford 2.6 g (89%) of the title compound as a white solid, m. p. 150°-15t°C.
BL. 7-Benzyloxy-2-methyl-3-(2-trimethylsilanyl-ethoxymethyls3Sbenzimidazole-5-carboxylic Acid Dimethylamide 5.8 g (13 mmol) 4-Benzyloxy-6-bromo-2-methyl-1- (2-trimethylsilanyl-ethoxymethyl)-1 N-benzimidazole, 1. 3 g (5.2 mmol) triphenylphosphine, 0.4 g (1.9 mmol) palladium (il) acetate.and 80 ml (160 mmol) dimethylamine (2M in THF) were transferred to an autoclave and carbonylated (6 bar COz) at 120° C for 16h. The
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catalyst was filtered off and the filtrate was concentrated in vacuo. The crystallization of the residue from diisopropyl ether afforded 3.7 g (65%) of the title compound as a white solid, m. p. 142"-146°C.
BM. 4-Benzyloxy-6-bromo-2-methyl-1-1 lAbenzimidazole 18.6 g (58.6 mmol) 4-Benzyloxy-6-bromo-2-methyl-1H-benzimidazole and 9 ml (70.3 mmol) triethyl-amine were suspended in 370 mi dichloromethane and 13.9 ml (70.3 mmol) (2-chloromethoxy-ethyl)-trimethyl- silane were added dropwise. The reaction was stirred at room temperature for 3h, poured into water (400 mi) and extracted with dichloromethane (3 x 100 mi). The organic layers were dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel (toluene/dioxane = 9:1) to afford 5.9 g (23%) of the title compound as a beige solid, m. p. 94°-95° C.
BN. 7-Hydroxy-6-((R)-3-hydroxy-3-phenyl-propylE2, 3-dimethyl-3bbenzimidazole-5-carboxylic Acid Dimethylamide In a flame-dried flask filled with argon, 0.8 g (2.2 mmol) 7-hydroxy-2, 3-dimethyl-6- (3-oxo-3-phenyi-propyl)- 3H-benzoimidazole-5-carboxylic acid dimethylamide were dissolved in 130 mi dry isopropanol and degassed with argon. 295 mg (2.2 mmol) tert-Butylate and 120 mg (5 mol-%) RuCI2 [ (S)-BINAP] [ (S)-DAIPEN] were added and the solution was transferred to an autoclave and hydrogenated at room temperature for 18h (40 bar). The reaction mixture was poured into a satured ammonium chloride solution (80 mi) and extracted with ethyl acetate (3 x 20 ml). The organic layers were dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel (dichloromethane/methanol = 9:1) to afford 0.4 g (50%) of the title compound as a green solid, m. p. 262°-264° C. [a ; D = + 62° (c = 0. 2 in CHCI3). Commercial utility The compounds of the formulae 1, 1 a and 2 and their pharmacologically acceptable salts (= active compounds according to the invention) have valuable pharmacological properties which make them commercially utilizable. In particular, they exhibit marked inhibition of gastric acid secretion and an excellent gastric and intestinal protective action in warm-blooded animals, in particular humans. In this connection, the active compounds according to the invention are distinguished by a high selectivity of action, an advantageous duration of action, a particularly good enteral activity, the absence of significant side effects and a large therapeutic range. "Gastric and intestinal protection"in this connection is understood as meaning the prevention and treatment of gastrointestinal diseases, in particular of gastrointestinal inflammatory diseases and lesions (such as, for example, gastric ulcer, peptic ulcer, including peptic ulcer bleeding, duodenal ulcer, gastritis, hyperacidic or medicament-related functional dyspepsia), which can be caused, for example, by microorganisms (e. g. Helicobacter pylori), bacterial toxins, medicaments (e. g. certain antiinflammatories and antirheumatics, such as NSAIDs and COX-inhibitors), chemicals (e. g. ethanol), gastric acid or stress situations. "Gastric and intestinal protection"is understood to include, according to general knowledge, gastroesophageal reflux disease (GERD), the symptoms of which include, but are not limited to, heartburn and/or acid regurgitation. In their excellent properties, the active compounds according to the invention surprisingly prove to be clearly superior to the compounds known from the prior art in various models in which the antiulcerogenic and the antisecretory properties are determined. On account of these properties, the active compounds according to the invention are outstandingly suitable for use in human and veterinary medicine, where they are used, in particular, for the treatment and/or prophylaxis of disorders of the stomach and/or intestine. A further subject of the invention are therefore the active compounds according to the invention for use in the treatment and/or prophylaxis of the abovementioned diseases. The invention likewise includes the use of the active compounds according to the invention for the pro- duction of medicaments which are employed for the treatment arid/or prophylaxis of-the abovementioned diseases. The invention furthermore includes the use of the 'active compounds according to the invention for the treatment and/or prophylaxis of the abovementioned diseases. A further subject of the invention are medicaments which comprise one or more active compounds according to the invention. The medicaments are prepared by processes which are known per se and familiar to the person skilled in the art. As medicaments, the active compounds according to the invention (= active compounds) are either employed as such, or preferably in combination with suitable pharmaceutical auxiliaries or excipients in the form of tablets, coated tablets, capsules, suppositories, patches (e. g. as TTS), emulsions, suspensions or solutions, the active compound content advantageously being between 0.1 and 95% and it being possible to obtain a pharmaceutical administration form exactly adapted to the active compound and/or to the desired onset and/or duration of action (e. g. a sustained-release form or an enteric form) by means of the appropriate selection of the auxiliaries and excipients. The auxiliaries and excipients which are suitable for the desired pharmaceutical formulations are known to the person skilled in the art on the basis of his/her expert knowledge. In addition to solvents, gel-forming agents, suppository bases, tablet auxiliaries and other active compound excipients, it is possible to use, for example, antioxidants, dispersants, emulsifiers, antifoams, flavor corrigents, preservatives, solubilizers, colorants or, in particular, permeation promoters and complexing agents (e. g. cyclodextrins). The active compounds can be administered orally, parenterally or percutaneously.
In general, it has proven advantageous in human medicine to administer the active compound (s) in the case of oral administration in a daily dose of approximately 0.01 to approximately 20, preferably 0.05 to 5, in particular 0.1 to 1.5, mg/kg of body weight, if appropriate in the form of several, preferably 1 to 4, individual doses to achieve the desired result. In the case of a parenteral treatment, similar or (in parti- cular in the case of the intravenous administration of the active compounds), as a rule, lower doses can be used. The establishment of the optimal dose and manner of administration of the active compounds necessary in each case can easily be carried out by any person skilled in the art on the basis of his/her expert knowledge. If the active compounds according to the invention and/or their salts are to be used for the treatment of the abovementioned diseases, the pharmaceutical preparations can also contain one or more pharma- coiogically active constituents of other groups of medicaments, for example : tranquillizers (for example from the group of the benzodiazepines, for example diazepam), spasmolytics (for example, bietamiverine or camylofine), anticholinergics (for example, oxyphencyclimine or phencarbamide), local anesthetics, (for example, tetracaine or procaine), and, if appropriate, also enzymes, vitamins or amino acids. To be emphasized in this connection is in particular the combination of the active compounds according to the invention with pharmaceuticals which inhibit acid secretion, such as, for example, H2 blockers (e. g. cimetidine, ranitidine), H/Kt ATPase inhibitors (e. g. omeprazole, pantoprazole), or further with so-called peripheral anticholinergics (e. g. pirenzepine, telenzepine) and with gastrin antagonists with the aim of increasing the principal action in an additive or
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super-additive sense and/or of eliminating or of decreasing the side effects, or further the combination with antibacterially active substances
such as, for example, cephalosporins, tetracyclines, penicillins, macrolides, nitroimidazoles or alternatively bismuth salts) for the control of slicobacter pylori. Suitable antibacterial co-components which may be mentioned are, for example, mezlocillin, ampicillin, amoxicillin, cefalothin, cefoxitin, cefotaxime, imipenem, gentamycin, amikacin, erythromycin, ciprofloxacin, metronidazole, clarithromycin, azithromycin and combinations thereof (for example clarithromycin + metronidazole). In view of their excellent gastric and intestinal protection action, the active compounds according to the invention are suited for a free or fixed combination with those medicaments (e. g. certain antiinflamma- tories and antirheumatics, such as NSAIDs), which are known to have a certain ulcerogenic potency. In addition, the compounds of formula 1 are suited for a free or fixed combination with motility-modifying drugs. Pharmacology The excellent gastric protective action and the gastric acid secretion-inhibiting action of the compounds according to the invention can be demonstrated in investigations on animal experimental models. The compounds according to the invention investigated in the model mentioned below have been provided with numbers which correspond to the numbers of these compounds in the examples. Testing of the secretion-inhibiting action on the defused rat stomach In Table A which follows, the influence of the compounds according to the invention on the pentagastrin- stimulated acid secretion of the perfused rat stomach after intraduodenal administration in vivo is shown.
Table A.




Methodology The abdomen of anesthetized rats (CD rat, female, 200-250 g ; 1. 5 g/kg i. m. urethane) was opened after tracheotomy by a median upper abdominal incision and a PVC catheter was fixed transorally in the esophagus and another via the pylorus such that the ends of the tubes just projected into the gastric lumen. The catheter leading from the pylorus led outward into the right abdominal wall through a side opening. After thorough rinsing (about 50-100 ml), warm (37°C) physiological NaCI solution was continuously passed through the stomach (0.5 mi/min, pH 6.8-6.9; Braun-Unita I). The pH (pH meter 632, glass electrode EA147 ; = 5 mm, Metrohm) and, by titration with a freshly prepared 0. Ot N NaOH solution to pH 7 (Dosimat 665 Metrohm), the secreted HCI were determined in the effluent in each case collected at an interval of 15 minutes. The gastric secretion was stimulated by continuous infusion of 1 g/kg (= 1.65 ml/h) of i. v. pentagastrin (left femoral vein) about 30 min after the end of the operation (i. e. after determination of 2 preliminary fractions). The substances to be tested were administered intraduodenally in a 2.5 ml/kg liquid volume 60 min after the start of the continuous pentagastrin infusion. The body temperature of the animals was kept at a constant 37.8-38°C by infrared irradiation and heat pads (automatic, stepless control by means of a rectal temperature sensor).



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We Claims ..
Compounds of formula 1,



.in which. Ri is hydrogen, halogen, hydroxyl, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, 1-4C- alkoxy, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkoxycarbonyl, 2-4C-alkenyl, 2-4C-alkynyl, fluoro-1-4C-alkyl, hydroxy-1 -4C-alkyl or mono- or di-1-4C-alkylamino, R2 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkyl, aryl, 3-7C-cycloalkyl, 3-7C-cyclo-


alkyl-1-4C-alkyl, 1-4C-alkoxycarbonyl, mono-or di-1-4C-alkylamino-1 -4C-alkylcarbonyl, hydroxy-1-




4C-alkyl, fluoro-2-4C-alkyl, R3 is hydrogen, halogen, fluoro-1-4C-alkyl, carboxyl, 1-4C-allkoxycarbonyl, hydroxy-1-4C-alkyl, 1-4C-


alkoxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkoxy-1-4C-alkyl, fluoro-1-4C-alkoxy-1-4C-alkyl, 1-4C-alkoxy-




1-4C-alkoxy, 1-4C-alkylcarbonylamino, 1-4C-alkylcarbonyl-N-1-4C-alkylamino, 1-4C-alkoxy-1-4C- alkylcarbonylamino or the group-CO-NR31 R32, where R31 is hydrogen, hydroxyl, 1-7C-alkyl, 3-7C-cycloalkyl, hydroxy-1-4C-alkyl or 1-4C-alkoxy-1-4C- alkyl and R32 is hydrogen, 1-7C-alkyl, 3-7C-cycloalkyl, hydroxy-1 -4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino, hydroxy-pyrrolidino, aziridino, azetidino, piperidino, piperazino, N-1-4C-alkylpiperazino or morpholino group, X is O (oxygen) or NH and Ar is a mono-or bicyclic aromatic residue, substituted by R4, R5, R6 and R7, which is selected from the group consisting of phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, indolyl, benzimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, pyridinyl, pyrimidinyl, chinolinyl and isochinolinyl, wherein R4 is hydrogen, 1-4C-alkyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy, 2-4C-alkenyloxy, 1-4C-alkylcarbonyl, carboxy, 1-4C-alkoxycarbonyl, carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl-1-4C-alkyl, halogen, hydroxy, aryl, aryl-1-4C-alkyl, aryl-oxy, aryl-1-4C-alkoxy, trifluoromethyl, nitro, amino, mono-or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonylamino, 1-4C-alkoxy-1-4C- alkoxycarbonylamino or sulfonyl, R5 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, R6 is hydrogen, 1-4C-alkyl or halogen and R7 is hydrogen, 1-4C-alkyl or halogen, and wherein aryl is phenyl or substituted phenyl with one, two or three same or different substituents from the group of 1-4C-alkyl, 1-4C-alkoxy, carboxy, 1-4C-alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and cyano, and the salts of these compounds.
2. Compounds of formula 1 according to claim 1, in which R1 is hydrogen, halogen, hydroxyl, 1-4C-alkyl, 3-7C-cycloalkyl, 3-7C-cycloalkyl-1-4C-alkyl, 1-4C- alkoxy, 1-4C- alkoxy-1 -4C-alkyl, 1 -4C-alkoxycarbonyl, 2-4C-alkenyl, 2-4C-alkynyl, fluoro-1-4C-alkyl, hydroxy-1 -4C-alkyl or mono-or di-1-4C-alkylamino, R2 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxy-1-4C-alkyl, aryl, 3-7C-cycloalkyl, 3-7C-cyclo- alkyl-1-4C-allkyl, 1-4C-alkoxycarbonyl, mono-or di-1-4C-alkylamino-1-4C-alkylcarbonyl, hydroxy-1- 4C-alkyl, fluoro-2-4C-alkyl, R3 is hydrogen, halogen, fluoro-1-4C-alkyl, carboxyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, 1-4C- alkoxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkoxy-1-4C-alkyl, fluoro-1-4C-alkoxy-1-4C-alkyl or the group- CO-NR31 R32, where R31 is hydrogen, hydroxyl, 1-7C-alkyl, hydroxy-1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl and R32 is hydrogen, 1-7C-alkyl, hydroxy-1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino, piperidino, piperazino, N-1-4C-alkylpiperazino or morpholino group, X is 0 (oxygen) or NH and Ar is a mono-or bicyclic aromatic residue, substituted by R4, R5, R6 and R7, which is selected from the group consisting of phenyl, naphthyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2, 3-triazolyl, indoxyl, benzimidazolyl, furyl, benzofuryl, thienyl, benzothienyl, thiazolyl, isoxazolyl, pyridinyl, pyrimidinyl, chinolinyl and isochinolinyl, wherein R4 is hydrogen, 1-4C-alkyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy, 2-4C-alkenyloxy, 1-4C-alkylcarbonyl, carboxy, 1-4C-alkoxycarbonyl, carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl-1-4C-alkyl, halogen, hydroxy, aryl, aryl-1-4C-alkyl, aryl-oxy, aryl-1-4C-alkoxy, trifluoromethyl! nitro, amino, mono-or di-1-4C-alkylamino, 1-4C-alkylcarbonylamino, i-4C-alkoxycarbonylamino, 1-4C-alkoxy-1-4C-alkoxycarbonylamino or sulfonyl, R5 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, halogen, trifluoromethyl or hydroxy, R6 is hydrogen, 1-4C-alkyl or halogen and R7 is hydrogen, 1-4C-alkyl or halogen, and wherein aryl is phenyl or substituted phenyl with one, two or three same or different substituents from the group of 1-4C-alkyl, 1-4C-aIkoxy, carboxy, 1-4C-alkoxycarbonyl, halogen, trifluoromethyl, nitro, trifluoromethoxy, hydroxy and cyano, and the salts of these compounds.
3. Compounds of formula 1 according to claim 1, in which Rl is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl or fluoro-1-4C-alkyl, R2 is hydrogen, 1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, R3 is hydrogen, halogen, carboxyl, 1-4C-alkoxycarbonyl, hydroxy-1 -4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkoxy-1-4C-alkyl, 1-4C-alkylcarbonyl-N-1-4C-alkylamino or the group -CO-NR31R32, where R31 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, hydroxy-1 -4C- alkyl or 1-4C-alkoxy-1-4C-alkyl and R32 is hydrogen or 1-4C-alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino, hydroxypyrrolidino, aziridino, azetidino, piperidino, piperazino, N-1 -4C-alkylpiperazino or morpholino group, X is 0 (oxygen) or NH and Ar is a phenyl group, substituted by R4, R5, R6 and R7, wherein R4 is hydrogen, 1-4C-alkyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy, 2-4C-alkenyloxy, 1-4C-alkylcarbonyl, carboxy, 1-4C-alkoxycarbonyl, carboxy-1-4C-alkyl, 1-4C-alkoxycarbonyl-1-4C-alkyl, halogen, hydroxy, trifluoromethyl, nitro, amino, mono-or di-1 -4C-alkylamino, 1-4C-alkylcarbonylamino, 1-4C-alkoxycarbonylamino, 1-
26

4C-alkoxy-1-4C-alkoxycarbonylamino or sulfonyl, R5 is hydrogen, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, halogen, trifluoromethyl or Hydroxy, R6 is hydrogen, 1-4C-alkyl or halogen and R7 is hydrogen, 1-4C-alkyl or halogen, and the salts of these compounds.
4. Compounds of formula 1 according to claim 1, characterized by the formula la,




in which R1 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl orfluoro-1-4C-alkyl, R2 is hydrogen, 1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, R3 is hydrogen, halogen, carboxyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, 1 -4 C- aIkoxy-1 -4 C-aIky 1,1-4C-alkoxy-1-4C-alkoxy-1-4C-alkyl, 1-4C-alkylcarbonyl-N-1-4C-alkylamino or the group -CO-NR31R32, where R31 is hydrogen, 1-4C-alkyl, 3-7C-cycloalkyl, hydroxy-1 -4C-all 5. Compounds formula 1a according to claim 4, in which R1 is 1-4C-alkyl, 3-7C-cycloalkyl or fluoro-1-4C-alkyl, R2 is hydrogen, 1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, R3 is hydrogen, carboxyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkoxy-1-4C- alkyl, 1-4C-alkylcarbonyl-N-1 -4C-alkylamino or the group-CO-NR31 R32, where R31 is hydrogen, 1-4C-alkyl, hydroxy-1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl and R32 is hydrogen or 1-4C-alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino, aziridino, azetidino or morpholino group, R4 is hydrogen, R5 is hydrogen and X is 0 (oxygen) or NH, and the salts of these compounds.
6. Compounds of formula 1a according to claim 4, in which Ri is 1-4C-alkyl, 3-7C-cycloalkyl or fluoro-1-4C-alkyl, R2 is 1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, R3 is carboxyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-aryl, 1-4C-alkoxy-1-4C- alkoxy-1-4C-alkyl, 1-4C-alkylcarbonyl-N-1 -4C-alkylamino or the group-CO-NR31 R32, where R31 is hydrogen, 1-4C-alkyl, hydroxy-1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl and R32 is hydrogen or 1-4C-alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino, hydroxypyrrolidino, aziridino, azetidino or morpholino group, R4 is hydrogen, R5 is hydrogen and X is 0 (oxygen) or NH, and the salts of these compounds.
7. Compounds of the formula 1 a according to claim 4, in which Ri is 1-4C-alkyl, R2 is 1-4C-alkyl, R3 is hydroxy-1 -4C-alkyl, 1-4C-alkoxy-1-4C-alkyl or the group-CO-NR31 R32, where R31 is hydrogen, 1-4C-alkyl, hydroxy-2-4C-alkyl or 1-4C-alkoxy-2-4C-alkyl and R32 is hydrogen, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino, group, R4 is hydrogen, R5 is hydrogen and X is 0 (oxygen) or NH, and the salts of these compounds.
8. Compounds of formula 1 a according to claim 4, in which RI is 1-4C-alkyl or fluoro-1-4C-alkyl, R2 is 1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, R3 is carboxyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkoxy-1-4C-alkylorthegroup-CO-NR31 R32, where R31 is hydrogen, 1-4C-alkyl, hydroxy-2-4C-alkyl or 1 -4C-alkoxy-2-4C-alkyl and R32 is hydrogen or 1-4C-alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino or morpholino group, R4 is hydrogen, R5 is hydrogen and X Is 0 (oxygen) or NH, and the salts of these compounds.
9. Compounds of formula 1 according to claim 1, .characterized by the formula 2,
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(2)

in which R1 is 1-4C-alkyl or 3-7C-cycloalkyl, R2 is hydrogen or 1-4C-alkyl, R3 is 1-4C-alkoxycarbonyl, hydroxy-1 -4C-aIkyl, 1-4C-alkoxy-1-4C-alkyl or the group-CO-NR31 R32, where R31 is hydrogen, 1-4C-alkyl, hydroxy-1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl and R32 is hydrogen or 1-4C-alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino, aziridino, azetidino or morpholino group, R4 is hydrogen, R5 is hydrogen and X is 0 (oxygen) or NH, and the salts of these compounds.
10. Compounds of formula 2 according to claim 9, in which Rl is 1-4C-alkyl, 3-7C-cycloalkyl or fluoro-1-4C-alkyl, R2 is 1-4C-alkyl or 1-4C-alkoxy-1-4C-alkyl, R3 is carboxyl, 1-4C-alkoxycarbonyl, hydroxy-1-4C-alkyl, 1-4C-alkoxy-1-4C-alkyl, 1-4C-alkoxy-1-4C- alkoxy-1-4C-alkyl, 1-4C-alkylcarbonyl-N-1-4C-alkylamino or the group-CO-NR31 R32, where R31 is hydrogen, 1-4C-alkyl, hydroxy-1 -4C-alkyl or 1-4C-alkoxy-1-4C-alkyl and R32 is hydrogen or 1-4C-alkyl, or where R31 and R32 together, including the nitrogen atom to which both are bonded, are a pyrrolidino, hydroxypyrrolidino, aziridino, azetidino or morpholino group, R4 is hydrogen, R5 is hydrogen and X is 0 (oxygen) or NH, and the salts of these compounds.
11. A medicament comprising a compound as claimed in claim 1 and/or a pharmacologically acceptable salt thereof together with customary pharmaceutical auxiliaries and/or excipients.
12. The use of a compound as claimed in claim 1 and its pharmacologically acceptable salts for the prevention and treatment of gastrointestinal disorders.
Dated this 28 th day of October ,2005

28

ABSTRACT
The invention relates to cyclic benzimidazoles of formula (1), (1) in which the substituents and symbols have the meanings indicated in the description. The compounds have gastric secretion inhibiting and excellent gastric and intestinal protective action properties.
To
The Controller of Patent
The Patent Office
Mumbai
29