MXPA01001720A - New compounds - Google Patents

Abstract

The present invention relates to novel compounds, and therapeutically acceptable salts thereof of formula (I), which inhibit exogenously or endogenously stimulated gastric acid secretion and thus can be used in the prevention and treatment of gastrointestinal inflammatory diseases.

Description

NEW IMIDAZO COMPOUNDS [l, 2-a] -PIRIDINE, FORMULATION PHARMACEUTICAL CONTAINING THEM AND USING THEM FOR THE MANUFACTURE OF A MEDICATION TECHNICAL FIELD The present invention relates to new compounds and to therapeutically acceptable salts thereof, which inhibit exogenously or endogenously stimulated gastric acid secretion and, thus, can be used in the prevention and treatment of gastrointestinal inflammatory diseases. . In other aspects, the present invention relates to the compounds for use in therapy; to processes for the preparation of such new compounds; to pharmaceutical compositions containing at least one compound according to the present invention or a therapeutically acceptable salt thereof, as an active ingredient; and to the use of the active compounds in the manufacture of medicaments for the aforementioned medical use. BACKGROUND OF THE INVENTION Substituted imidazo [1, 2-a] -pyridines useful in the treatment of peptic ulcers are known in the art, e.g. European Patent EP-B-0033094 and US Patent 4,450,164 (Schering Corporation); Ref: 127102 by the European Patent EP EP-B-0204285 and the US Patent US 4,725,601 (Fujisawa Phar aceutical Co.); and by the publications of J. J. Kaminski et al. in Journal of Medical Chemistry (vol 28, 876-892, 1985; vol 30, 5 2031-2046, 1987; vol 30, 2047-2051, 1987; vol 32, 1686-1700, 1989; and vol. 34, 533-541, 1991). To review the pharmacology of the gastric acid pump (H +, K + -ATPase), see Sachs et al. , (1995) Annu. Rev. Pharmacol. Toxicol 35: 277-305. DESCRIPTION OF THE INVENTION Surprisingly it has been found that the compounds of the formula I or a pharmaceutically acceptable salt thereof, are particularly effective as inhibitors of H +, K + -ATPase and therefore inhibitors of gastric acid secretion. Thus, in one aspect, the present invention relates to compounds of the general formula I | g | ^^^^^^^ || ^ | ¡j ^^ ía ^^^^^^^^^ g ^^ or a pharmaceutically acceptable salt thereof, wherein R1 is (a) H, ( b) CH3, or (c) CH2OH, R2 is alkyl of 1 to 6 carbon atoms; R3 is alkyl of 1 to 6 carbon atoms; R4 is (a) H, or (b) halogen; R5 is (a) H, or (b) alkyl of 1 to 6 carbon atoms; R6 is (a) H, (b) alkylcarbonyl of 1 to 6 carbon atoms, J ^? &J (c) cycloalkylcarbonyl of 3 to 7 carbon atoms, in which the cycloalkyl group is optionally substituted with one or more substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), (d) Aryl-alkylcarbonyl of 1 to 6 carbon atoms, in which the aryl radical represents a phenyl group , pyridyl, thienyl or furanyl, optionally substituted with one or more substituents which are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- ( 1 to 6 carbon atoms), (e) alkoxy of 1 to 6 carbon atoms-alkylcarbonyl of 1 to 6 carbon atoms, (f) alkoxycarbonyl of 1 to 6 carbon atoms, (g) arylcarbonyl in which the Aryl group represents phenyl, pyridyl, thienyl or furanyl, optionally substituted with one or more substituy is that they are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), (h) cycloalkyl of 3 to 7 carbon atoms - alkylcarbonyl of 1 to 6 carbon atoms, in which the The cycloalkyl group is optionally substituted with one or & e s ^ ** - < > - ^^ i. , ^. * "... ^. ^. ^., ^ ..... - *, | f. l ^^^^^ ^^^^^ Ul to ^^^ ^ ¿^ t? ^ ^^ IJD? ^ more substituents B selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), 5 (i) alkoxy of 1 to 6 carbon atoms- alkoxycarbonyl of 1 to 6 carbon atoms, (j alkoxy 1 to 6 carbon atoms-alkoxy of 1 to 6 carbon atoms-alkylcarbonyl of 1 to 6 carbon atoms, 10 (k) a carbamoyl group of the formula wherein R7, R8 are the same or different and represent H, or alkyl of 1 to 6 carbon atoms, (1) R9- (alkylcarbonyl of 1 to 6 carbon atoms), wherein R9 is HOC = 0-, alkyl (from 1 to 6 carbon atoms) -O- C = 0-, or an amino group of the formula R.R7 wherein R7, R8 are the same or different and represent H or alkyl of 1 to 6 carbon atoms, (m) Hydroxylated R9-alkylcarbonyl (1-6 carbon atoms), (n) R9-alkenylcarbonyl having 1 to 6 carbon atoms, 5X is (a) NH, or (b) 0. As used in present, the term "alkyl of 1 to 6 carbon atoms" denotes a group Straight or branched chain alkyl having from 1 to 6 carbon atoms. Examples of such alkyl groups of 1 to 6 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl and pentyl and hexyl straight and branched chain. The term "halogen" as used herein includes fluoro, chloro, bromo and iodo radicals. The term "pyridyl" includes the 2-, 3- and 4- isomers, and the terms "thienyl" and "furanyl" include the 2- and 3- isomers. Both pure enantiomers, racemic mixtures and unequal mixtures of two enantiomers are within the scope of the present invention. It should be understood that all possible diastereomeric forms (pure enantiomers, racemic mixtures and mixtures unequal of two enantiomers) remain within the scopes of the present invention. Also included in the invention are derivatives of the compounds of the formula I having the biological function of the compounds of the formula I. Depending on the process conditions and the final products of formula I, these are obtained either in neutral form or in the form of a salt. Both the free base and the salts of these final products are within the scope of the present invention. The acid addition salts of the new compounds, in a manner known per se, can be transformed into the free base using basic agents such as alkalis, or by ion exchange. The free base obtained can also form salts with organic or inorganic acids. In the preparation of the acid addition salts, acids are preferably used in such a way that they form therapeutically acceptable and suitable salts. Examples of such acids include halohydric acids such as hydrochloric acid; sulfuric acid, phosphoric acid, nitric acid; aliphatic carboxylic acids or sulfonic acids, alicyclic, aromatic or heterocyclic such as formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, "- & * ^ ^ t ^ e ^ s & & it * hydroxymaleic acid, pyruvic acid, p- hydroxybenzoic embonic acid, methanesulfonic acid, ethanesulfonic acid, hydroxyethane acid, halobencensulfónico acid, toluenesulfonic acid or acid.? 5 naphthalenesulfonic. Preferred compounds according to the present invention are those of the formula I wherein R 1 is CH 3 or CH 2 OH; R2 is CH3 or CH2CH3; R3 is CH3 or CH2CH3; R4 is H, Br, Cl or F; R5 is H or CH3. 10 particularly preferred compounds according to the present invention are: 8- (2, 6-dimethylbenzylamino) -2-hydroxymethyl-3- methylimidazo [1, 2-a] pyridine 8- (2-ethyl-6-methylbenzylamino) - 3-15 2-hydroxymethyl-methylimidazo [1, 2-a] pyridine 8- (2, 6-dimethylbenzylamino) -3, 6-dimethyl-2- hydroxymethylimidazo [1, 2-a] pyridine acetate [8- (2 , 6-dimethylbenzylamino) -3- methylimidazo [1, 2-a] pyridin-2-yl] -methyl ethylcarbonate 20 [8- (2, 6-dimethylbenzylamino) -3- methylimidazo [1, 2-a] pyridine 2-yl] -methyl N, N-dimethylcarbamate of [8- (2,6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] pyridin-2-yl] -methyl] feA ^ a - ^^ a ^? ^ a ^ Wsiiis ^ -B ^ aBBa ^ aiW ». ^, ~ .-. w .. 3-ethylmalonate of 1- [[8- (2,6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] -pyridin-2-yl] -methyl] 4- [[8- (2,6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] -pyridin-2-yl] -methoxy] -4-oxobutanoic acid 4- [[8- (2-ethyl-6-methylbenzylamino) -3-methylimidazo [1,2- a] pyridin-2-yl] -methoxy] -4-oxobutanoic acid 5- [[8 - (2,6-dimethylbenzylamino) -3-methylimidazo [1,2-a] pyridin-2-yl] -methoxy] -5-oxopentanoic acid 2- (dimethylamino) -acetate of [8- (2,6-dimethylbenzylamino) 3-methylimidazo [1,2-a] pyridin-2-yl] -methyl 8- (2,6-dimethylbenzylamino) -2,3-dihydroxymethylimidazo [1,2-a] pyridine. Preparation The present invention also provides the following processes A and B for the manufacture of compounds of the general formula I. The process A for the manufacture of the compounds of the general formula I comprises the following steps: a) the imidazo [1,2-a] pyridine compounds of the formula II Where is a lower alkyl group, R represents H, CH3 or an ester group such as COOCH3, COOC2H5, etc., Xi is NH 2 or OH and R 5 is as defined for formula I, they can be prepared by reacting compounds 5 of the general formula III with compounds of the general formula IV wherein Z is a leaving group such as a halogen, mesyl or tosyl group. The reaction is carried out under standard conditions in a solvent such as acetone, acetonitrile, alcohol, N, -dimethylformamide, etc. with or without a base, b) the compounds of the formula II can be react with compounds of the formula V wherein R2, R3 and R4 are as defined for formula I and Zi is a leaving group, such as a halogen group, tosyl or mesyl, under standard conditions in an inert solvent, with or without a base, to obtain the compounds of the formula VI Wherein R 2, R 3, R 4 'R 5 and X are as defined for formula I, Y is a lower alkyl group and R is H, CH 3 or an ester group such as COOCH 3, COOC 2 H 5, and so on. c) The reduction of the compounds of the general formula VI, e.g. using lithium aluminum hydride or Red-Al in an inert solvent such as tetrahydrofuran, ether or toluene, produces the compounds of the general formula I wherein R6 is H. d) The substituent R6 of the compounds of the formula I (R6? H) can be introduced through standard acylation procedures carried out under normal conditions, e.g. by reacting the compounds of the formula I wherein R6 is H, with an acid, an acid halide or the anhydride of R6 (R6? H).

The process B for the manufacture of the compounds of the general formula I comprises the following steps: a) in compounds of the formula I wherein R6 is H, the hydroxymethyl group can be halogenated by standard methods in an inert solvent, to obtain the corresponding alomethyl group of formula VII b) The substituent R6 of the compounds of the formula I (R6? H) can be introduced by reacting compounds of formula VII with the corresponding acid of R6 (R6? H). The reaction is carried out under standard conditions in an inert solvent, with or without a base. Medical Use In a further aspect, the present invention relates to compounds of the formula I for use in therapy, particularly for use against gastrointestinal inflammatory diseases. The present invention also provides the use of a compound of the formula I in the manufacture of a medicament for the inhibition of gastric acid secretion or for the treatment of gastrointestinal inflammatory diseases. The compounds according to the present invention, therefore, can be used for the prevention and treatment of gastrointestinal inflammatory diseases and diseases related to gastric acid, in mammals, including humans, such as gastritis, gastric ulcer, duodenal ulcer, esophageal reflux and Zollinger-Ellison syndrome. In addition, the compounds can be used for the treatment of other gastrointestinal disorders where a gastric antisecretory effect is desirable, e.g. in patients with gastrinomas and in patients with acute upper gastrointestinal hemorrhage. They can also be used in patients who are in intensive care, preoperatively and postoperatively, to prevent acid aspiration and stress ulcerations. The typical daily dose of the active substance varies within a wide range and will depend on various factors such as, for example, the individual requirements of each patient, the route of administration and the disease. In general, oral and parenteral doses will be within the range of 5 to 1000 mg per day of the active substance. | j¿É & ^^^^ ^^^^^^ ^ ^ ^ | Pharmaceutical Formulations In a further aspect, the present invention relates to pharmaceutical compositions containing at least one compound of the present invention or a therapeutically acceptable salt thereof., as an active ingredient. The compounds according to the present invention can also be used in formulations together with other active ingredients, e.g. antibiotics such as amoxicillin. For clinical use, the compounds of the present invention are prepared in pharmaceutical formulations for oral, rectal, parenteral or other administration route. The pharmaceutical formulation contains a compound of the present invention in combination with one or more pharmaceutically acceptable ingredients. The vehicle can be in the form of a solid, semi-solid or liquid, or a capsule. These pharmaceutical preparations are another object of the present invention. Normally the amount of active compounds is between 0.1 and 95% by weight of the preparation, preferably between 0.1 and 20% by weight of the preparation for parenteral administration and preferably between 0.1 and 50% by weight in preparations for oral administration.

SjáSSSE * ~ In the preparation of pharmaceutical formulations containing a compound of the present invention in the form of dosage units for oral administration, the selected compound can be mixed with solid, powdery ingredients, such as lactose, sucrose, sorbitol, mannitol, starch, amylopectin, cellulose derivatives, gelatin or other suitable ingredient, as well as disintegrating and lubricating agents such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylene glycol waxes. Then, the mixture is processed to obtain granules or compressed to form tablets. Soft gelatin capsules can be prepared with capsules containing a mixture of the active compound or compounds of the present invention, vegetable oil, fat or any other suitable vehicle for the soft gelatine capsules. Hard gelatin capsules may contain granules of the active compound. Hard gelatin capsules may also contain the active compound in combination with solid powdered ingredients such as lactose, sucrose, sorbitol, mannitol, potato starch, corn starch, amylopectin, cellulose derivatives or gelatin. Dosage units for rectal administration can be prepared (i) in the form of suppositories containing the active substance mixed with a fatty base ^ ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡ (ii) in the form of a rectal gelatin capsule containing the active substance mixed with a vegetable oil, paraffin oil or any other suitable vehicle for rectal gelatin capsules; (iii) in the form of a ready-to-use microenema; or (iv) in the form of a dehydrated microenema to be reconstituted in a suitable solvent just before its administration. Liquid preparations for oral administration can be prepared in the form of syrups or suspensions, e.g. solutions or suspensions containing from 0.1 to 20% by weight of the active ingredient and the remainder consisting of sugar or sugar alcohols and a mixture of ethanol, water, glycerol, propylene glycol and polyethylene glycol. If desired, such liquid preparations may contain coloring, flavoring, saccharin and carboxymethylcellulose or other thickening agents. Liquid preparations for oral administration can also be prepared in the form of dehydrated powders to be reconstituted with a suitable solvent before use. Solutions for parenteral administration can be prepared in the form of a solution of a compound of the present invention with a pharmaceutically acceptable solvent, preferably in a concentration of 0.1 to 10% by weight. These solutions may also contain stabilizing ingredients and / or ingredients to regulate ^^^^^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^^^^ rgBffi_rtmHpliípíi ^ T ^ Míi ?? .r ~ *? pH and are divided into dosage units in the form of ampoules or flasks. Solutions for parenteral administration can also be prepared as dehydrated preparations to be reconstituted with a suitable solvent, extemporaneously before use. The compounds according to the present invention can also be used in formulations together with other active ingredients, e.g. for the treatment or prophylaxis of disorders including Helicobacter pylori infections of the human gastric mucosa. These other active ingredients can be antimicrobial agents, in particular: • β-lactam antibiotics such as amoxicillin, ampicillin, cephalothin, cefaclor or cefixime; • macrolides such as erythromycin or clarithromycin; • tetracyclines such as tetracycline or doxycycline; • aminoglycosides such as gentamicin, kanamycin or amikacin; • quinolones such as norfloxacin, ciprofloxacin or enoxacin; • others such as metronidazole, nitrofurantoin or chloramphenicol; or & Z £ * •, ^ - ^ ¿^^^ Ú Xf? * ^ * ^ * ^ • preparations containing bismuth salts such as bismuth subcitrate; bismuth subsalicylate, bismuth subcarbonate, bismuth subnitrate or bismuth subgalate. The compounds according to the present invention can also be used together or in combination for simultaneous administration, separately or sequentially, with antacids such as aluminum hydroxide, magnesium carbonate and aluminum hydroxide, or alginic acid, or together with or in combination for simultaneous administration, separately or sequentially, with pharmaceutical compounds that inhibit acid secretion, such as H2 blockers (eg cimetidine, ranitidine), H + / K + -ATPase inhibitors (eg omeprazole, pantoprazole, lansoprazole or rebeprazole), or together with or in combination for simultaneous administration, separately or sequentially, with gastroprokinetic compounds (eg cisapride or mosapride). EXAMPLES 20 1. PREPARATION OF THE COMPOUNDS OF THE PRESENT INVENTION Ex empl 1. 1 Synthesis of 8- (2f 6-dimethyl-l-benzylamino) -2-hydroxymethyl-3-methylimidazo [1,2-a] -pyridine A ^^^. ^^^. ^^^^^^, ^; .. ^^^^ -...,.; , ^^^ ^^^ 8 -. ^ ^^^^ a ^ .S ^^^ ^^ fa 8- (2, 6-dimethylbenzylamino) -3- methylimidazo [1, 2-a] pyridine Ethyl 2-carboxylate (5.2 g, 0.015 mol) in tetrahydrofuran (100 ml) and LiAlH4 (1.15 g, 0.03 mol) was added. After stirring the mixture at room temperature for 45 minutes, 1.15 ml of water was added dropwise, followed by 1.15 ml of 15% sodium hydroxide and then 3.45 ml of water. The solids were removed by filtration and washed well with methylene. The filtrate and washings were combined and the combined dried and the solvents were removed under reduced pressure. Purification of the residue by silica gel column chromatography using methylene chloride / methanol (10: 2) as eluent yielded 3.2 g (73%). of the title compound. XH-NMR (300 MHz, DMSO-d6): d 2.35 (s, 6H) 2.4 (s, 3H), 4.35 (d, 2H), 4.5 (d, 2H), 4.85 (t, 1H), 4.9 (t , 1H), 6.3 (s, 1H), 6.8 (t, 1H), 7.05-7.2 (m, 3H), 7.55 (d, 1H). Example 1 . 2 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ The synthesis of 8- (2-ethyl-6-methylbenzylamino) -2-hydroxymethyl-3-methylimidazo [1,2-a] pyridine.

To a suspension of LiAlH4 (0.24 g, 6.4 mmol) in anhydrous tetrahydrofuran (25 mL, under an argon atmosphere, 8- (2-ethyl-6-dimethylbenzylamino) -3- was added dropwise over a period of 30 minutes. methylimidazo [1,2-a] pyridine-2-carboxylic acid ethyl ester (1.1 g, 3.2 mmol) dissolved in anhydrous tetrahydrofuran (25 mL) After stirring the mixture at room temperature for 4 hours, 0.24 mL of water, followed by 0.24 ml of 15% sodium hydroxide and then 0.75 ml of water The solids were removed by filtration and washed well with tetrahydrofuran and with methylene chloride / methanol (9: 1). were combined and the combined was dried and the solvents were removed under reduced pressure.The residue was purified by silica gel column chromatography, using methylene chloride / methanol (9: 1) as eluent.The treatment of the residue with acetonitrile Ai ^. and after filtration, 0.76 g (77%) of the title compound was obtained. X H NMR (300 MHz, CDC13): d 1.2 (t, 3 H), 2.3 (s, 3 H), 2.4 (s, 3 H), 2.75 (q, 2 H), 4.35 (d, 2 H), 4.45 (s, 2 H) ), 4.75 (bs, 1H), 5.45 (t, 1H), 6.2 (d, 1H), 6.75 (t, 1H), 7.05-7.25 (m, 4H). Example 1.3 Synthesis of 8- (2,6-methylbenzylamino) -3,6-dimethyl-2-hydroxymethylimidazo [l r 2-a] pyridine To a suspension of LiAlH (0.19 g, 5.1 mmol) in anhydrous tetrahydrofuran (15 ml) under an argon atmosphere, 8- (2-ethyl-6-dimethylbenzylamino) -3 was added dropwise over a period of 30 minutes. 6-dimethylimidazo [1,2-15 a] pyridine-2-carboxylic acid ethyl ester (0.9 g, 2.6 mmol) dissolved in anhydrous tetrahydrofuran (15 ml). After stirring the mixture at room temperature for 2 hours, 0.2 ml of water was added dropwise, followed by 0.2 ml of 15% sodium hydroxide and then 0.6 ml of water. The solids are gga ^ g & s ^ ii ^ kfa ^^^^^^^^ if ^^^^^^^^^^^^^ removed by filtration and washed well with clpruro methylene chloride / methanol (1: 1). The filtrate and washings were combined and the combined dried and the solvents were removed under reduced pressure. The residue was purified by silica gel chromatography using methylene chloride / methanol (9: 1) as eluent. Treatment of the residue with acetonitrile and after filtration gave 0.36 g (77%) of the title compound. 10 XH NMR (300 MHz, CDC13): d 2.35 (s, 6H), 2.4 (s, 6H), 4.35 (d, 2H), 4.45 (s, 2H), 5.25 (t, 1H), 6.1 (s, 1H), 7.0-7.2 (m, 4H). Example 1 . 4 Synthesis of [8- (2, 6- 15 dimethylbenzylamine) -3-methylimidazo [1,2-a] pyridin-2-yl] -methyl acetate To a solution of 8- (2, 6-dimethylbenzylamino) -2- hydroxymethyl-3-methylimidazo [1, 2-a] pyridine (0.3 g, 1.0 20 mmol) and triethylamine (0.014 ml, 1.0 mmol) in chloride ^^ 7 ^,. ^., -, ^. ,. -. ¿^ ^ ^^, r. ,, .. z :. . ? T ^ - ..... ^ -,, ^^^^^ gl ^^^^^^^^^^^^^^^^^^ amp^ methylene (10 ml), acetyl chloride (0.071 ml, 1.0 mmol) was added dropwise. The reaction mixture was stirred for 1.5 hours at room temperature. Water was added and the organic phase was separated, washed with a solution of sodium bicarbonate, dried (Na 2 SO 4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using diethyl ether as eluent. Recrystallization from diethyl ether yielded 0.16 g (47%) of the desired product. 10 2 H NMR (300 MHz, CDC13): d 2.05 (s, 3H), 2.4 (s, 6H), 2.45 (s, 3H), 4.35 (d, 2H), 4.95 (bs, 1H), 5.2 (s, 2H), 6.25 (d, 1H), 6.8 (t, 1H), 7.05-7.2 (m, 3H), 7.3 (d, 2H). Example 1 . 5 15 Synthesis of [8- (2,6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] pyridin-2-yl] -methylcarbonate 8- (2,6-Dimethylimidazo-2-hydroxymethyl-3-methylimidazo [1,2-a] pyridine (0.4 g, 1.3 , ^^^. a ^^^ .-, - »^^^^^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ methylene chloride (20 ml) and the mixture was refluxed for 3 hours. An additional amount of ethyl chloroformate (0.13 ml, 1.3 mmol) was added and the reaction mixture was refluxed for 20 hours. A solution of sodium bicarbonate was added, the organic phase was separated, dried (Na2SO4) and evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel using diethyl ether as After elution and after crystallization from diethyl ether / petroleum ether (1: 2), 0.11 g (23%) of the title compound was obtained. XH NMR (300 MHz, CDC13): d 1.25 (t, 1H), 2.4 (s, 6H), 2.5 (s, 3H), 4.15 (q, 2H), 4.35 (d, 2H), 4.95 (bs, 1H), 5.25 (2H), 6.25 (d, 1H), 6.8 (t, 1H), 7.05-7.2 (m, 3H), 7.3 (d, 1H). Ex empl o 1. 6 Synthesis of [8- (2,6-dimethylbenzylamino) 3-methyl-midazo [1,2-a] pyridin-2-yl] - 20 N, N-dimethylcarbamate 8- (2,6-diemylbenzylamino) -2-hydroxymethyl-3-methylimidazo [1,2-a] pyridine (0.1 g, 0.34 mmol), dimethylcarbamyl chloride (0.03 m, 0.34 mmol), 5 sodium carbonate were added. (0.1 g, 0.94 mmol) and a catalytic amount of N, N-dimethylaminopyridine, to acetonitrile (15 ml) and the mixture was refluxed for 20 hours. An additional amount of dimethylcarbamyl chloride (0.15 ml, 1.7 mmol) was added and the mixture of The reaction was refluxed for 24 hours. The solids were removed by filtration and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate / petroleum ether (2: 1) as eluent, obtaining 0.07 g (56%) of the title compound. XH NMR (300 MHz, CDC13): d 2.4 (s, 6H) ', 2.5 (s, 3H), 2.85 (d, 6H), 4.35 (d, 2H), 4.9 (bs, 1H), 5.2 (s, 2H), 6.25 (d, 1H), 6.75 (t, 1H), 7.05-7.15 (m, 3H), 7.3 (d, 1H). Example 1 . 7 '^^^^^^^^^^^^^^^^^^^^^^^^^^ M Synthesis of l - [[8- (2,6-dimethylbenzylamino) 3-ethylmalonate) -3-methylimidazo [1,2- a] pyridin-2-yl] -methyl 8- (2,6-diemylbenzylamino) -2-hydroxymethyl-3-methylimidazo [1,2-a] pyridine (0.45 g, 1.5 mmol), ethylmalonyl chloride (0.23 g, 1.5 mmol) and sodium carbonate ( 0.32 g, 3.0 mmol) to methylene chloride (20 ml) and the mixture was stirred for 3 hours at room temperature. Water was added and the organic phase was separated, dried (Na2SO4) and evaporated under reduced pressure. Purification of the residue by silica gel column chromatography using diethyl ether as eluent and after crystallization from petroleum ether, 0.34 g (56%) of the desired product was obtained. XH NMR (300 MHz, CDC13). d 1.2 (t, 3H), 2.4 (s, 6H9, 2.55 (s, 3H), 3.4 (s, 2H), 4.15 (q, 2H), 4.35 (d, 2H), 4.9 (t, 1H), 5.25 (s, 2H), 6.25 (d, 1H), 6.8 (t, 1H), 7.05-7.15 (m, 3H), 7.35 (d, 1H) Example 1. * -as & ^. j ^ s ^ s ^ Synthesis of 4- * f [8- (2,6-dimethylbenzylamino) 3-methylimidazo [l, 2-a] pyridin-2-yl) -methoxy] -4 Oxobutanoic To a suspension of 8- (2,6-dimethylbenzylamino) -2-hydroxymethyl-3-methylimidazo [1,2-a] pyridine (0.2 g, 0.68 mmol) in acetonitrile (10 mL) was added hydride. sodium (50% in oil) (0.036 g, 0.75 mmol) and the mixture was stirred for 5 minutes. To the mixture was added succinic anhydride (0.1 g, 1.0 mmol) and the reaction mixture was refluxed for 20 hours. The solvent was evaporated under reduced pressure. Water was added to the residue and the solid that formed was isolated by filtration and washed with acetonitrile, to obtain 0.24 g (89%) of the title compound. XH NMR (300 MHz, CDC13): d 2.35-2.55 (m, 13H), 4. 35 (s, 2H), 4.9 (bs, 2H), 5.2 (s, 2H) 6.25 (d, 1H), 6.8 (t, 1H), 7.07-7.1 (m, 3H), 7.25 (d, 1H). Example 1 . 9 Synthesis of 4- [[8- (2-ethyl-6-methylbenzlamino) -3-methylimidazo [1,2- a] pyridin-2-yl] -methoxy] -4-oxobutanoic acid To a suspension of 8- (2-ethyl-6-methylbenzylamino) -2-hydroxymethyl-3-methylimidazo [1, 2-a] pyridine (0.47 g, 1.5 mmol) in acetonitrile (20 ml) was added hydride. sodium (50% in oil) (0.081 g, 1.7 mmol) and the mixture was stirred for 5 minutes. To the mixture was added succinic anhydride (0.23 g, 2.3 mmol) and the reaction mixture was refluxed for 20 hours. The solvent was evaporated under reduced pressure. The residue was suspended in water and the pH was adjusted to 6 with 2M HCl and the solid that formed was isolated by centrifugation. After washing with water and with acetonitrile, 0.51 g (82%) of the desired product was obtained. XH NMR (300 MHz, CDC13): d 1.2 (t, 1H), 2.35-2.55 (m, 10H), 2.7 (q, 2H), 4.3 (s, 2H), 5.2 (s, 2H), 6.25 (d , k 1H), 6.8 (t, 1H), 7.0-7.2 (m, 3H), 7.3 (d, 1H). Example 1 . 10 Synthesis of 5-ffé- (2,6-dimethylbenzylamino) -3-methylimidazo [1,2- a] pyridin-2-yl] -methoxy J-5-oxopentanoic acid To a solution of 8- (2,6-dimethylbenzylamine) ) -2-hydroxymethyl-3-methylimidazo [1,2-a] pyridine (0.3 g, 1.0 mmol) in tetrahydrofuran (10 ml), sodium hydride (50% in oil) was added (0.054 g, 1.1 mmol) ) and the mixture was stirred for 10 minutes. To the mixture was added glutaric anhydride (0.13 g, 1.1 mmol) and the reaction mixture was refluxed for 20 hours. The solvent was evaporated under reduced pressure. The residue was extracted by partition in dichloromethane and water. The pH was adjusted to 4 with 2M HCl. The organic phase was separated, dried (Na2SO4) and evaporated under reduced pressure. Purification of the residue by silica gel column chromatography using dichloromethane / methanol (94: 6) as eluent afforded 0.034 g (8%) of the title compound. XH NMR (300 MHz, CDC13): d 1.75 (t, 2H), 2.1 (t, 2H), 2.3 (t, 2H), 2.35 (s, 6H), 2.45 (s, 3H), 4.3 (s, 2H) ), 5.2 (s, 2H), 5.5 (bs, 1H), 6 ^ (d, 1H), 6.8 (t, 1H), 7.0- 7.15 (m, 3H), 7.3 (d, 1H). Example 1 . 11 Synthesis of [8- (2,6-dimethylbenzylamino) -3-methylimidazo [l, 2-a] pyridin-2-yl] -methyl 2- (dimethylamino) -acetate 8- (2,6-Dimethylbenzylamino) -2-chloromethyl-3-methylimidazo [1,2-a] pyridine (0.3 g, 1.0 mmol) was added. and N, N-dimethylglycine (0.1 g, 1.0 mmol) to acetonitrile (10 mL) and the mixture was refluxed for 20 hours. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel using dichloromethane / methanol (10: 2) as eluent. The Recrystallization from acetonitrile yielded 0.12 g (32%) of the title compound. L NMR (300 MHz, CD3OD): d 2.4 (s, 6H), 2.55 (s, 3H), 3.25 (s, 6H9, 3.85 (s, 2H), 4.4 (s, 2H), 4.9 (s, 2H) , 6.5 (d, 1H), 6.95 (t, 1H), 7.05-7.15 (m, 3H), 7.6 (d, 1H).

Example 1. 12 Synthesis of 8- (2,6-dimethylbenzylamino) -2,3-dihydroxymethylimidazo [1,2-a] pyridine To an ice-cooled solution of 2,3- 5-dicarboxylate of 8- (2,6-diemylbenzylamino) -imidazo [1, 2- a] pyridine (2.5 g, 6.3 mmol) in toluene (100 ml) was added Red-Al (14 ml, 45 mmol) (65% in toluene) over a period of 3 hours. The temperature was allowed to rise to room temperature and then a solution of Rochell salt (35 g of sodium and potassium tartrate in 250 ml of H20). The organic phase was separated, dried and evaporated under reduced pressure. Purification of the residue by silica gel column chromatography using dichloromethane / isopropyl alcohol (4: 1) yielded 0.09 g (5%) of the desired product. H NMR (300 MHz, CDC13): d 2.4 (s, 6H), 4.45 (s, 2H), 4.7 (s, 2H), 4.95 (s, 2H), 6.5 (d, 1H), 6.9 (t, 1H), 7.05-7.2 (m, 3H), 7.75 (d, 1H). 2. PREPARATION OF INTERMEDIARIES 20 Example 2. 1 & ^^^^^^^^^^^^^^^^^^ Synthesis of 8-amino-3-methylimidazo-2-carboxylate [1, 2-a ] pyridine A solution of 2,3-diaminopyridine (6.8 g, 62 mmol) and 3-bromo-2-oxobutyric acid ethyl ester (13 g, 62 mmol) in 1,2-dimethoxyethane (150 ml) was refluxed for 2 hours. Sodium carbonate (6.5 g) was added, 62 mmol) and the mixture was refluxed for 2 hours. The solids were isolated by filtration and washed with dichloromethane / methanol (10: 1). The filtrate and washings were combined and the solvents were removed under reduced pressure. The oily residue was washed with petroleum ether and purified twice by silica gel column chromatography using 1) dichloromethane / methanol (10: 1) and 2) ethyl acetate as eluent, to obtain 4.6 g (34%) of the title compound. XH NMR (300 MHz, CDC13): d 1.45 (t, 3H), 2.75 (s, H), 4.5 (q, 2H), 4.65 (bs, 2H), 6.35 (d, 1H), 6.7 (t, 1H ), 7.35 (d, 1H). Example 2. Synthesis of ethyl 8- (2,6-dimethylbenzylamino) -3-methylimidazo fl, 2-a] pyridine-2-carboxylate. 8-amino-3-methylimidazo [1,2-a] pyridine was added. Ethyl 2-carboxylate (4.6 g, 21 mmol), 2,6-dimethylbenzyl chloride (3.2 g, 21 mmol), sodium carbonate (4.4 g, 42 mmol) and a catalytic amount of potassium iodide, in acetonitrile ( 50 ml) and the mixture was refluxed for 3 hours. The reaction mixture was stirred for 20 hours at room temperature and refluxed for 1 hour. The solids were removed by filtration and the solvents were evaporated under reduced pressure. The residue was dissolved in methylene chloride and washed with water. The organic phase was separated, dried (Na2SO4) and evaporated under reduced pressure. Purification of the residue by silica gel column chromatography using methylene chloride / methanol (10: 1) as eluent and after crystallization from ethyl acetate gave 4.0 g (56%) of the desired product. ? E NMR (300 MHz, CDC13): d 1.4 (t, 3H), 2.4 (s, 6H), 2.75 (s, 3H), 4.35 (d, 2H), 4.45 (q, 2H), 5.15 (t, 1H), 6.25 (d, 1H), 6.85 (t, 1H), 7.05-7.2 (m, 3H), 7.35 (d, 1H). Example 2.3 Synthesis of ethyl 8- (2-ethyl-6-methylbenzylamino) -3-methylimidazofl, 2-a] pyridine-2-carboxylate To a stirred mixture of 8-amino-3-methylimidazo [1, 2 -a] ethyl pyridine-2-carboxylate (1.53 g, 7. 0 mmol) in methanol (25 ml) was added 2-ethyl-6-methylbenzaldehyde (1.1 g, 7.1 mmol), zinc chloride (II) (1.1 g, 8.0 mmol) in methanol (10 ml) and sodium cyanoborohydride. (0.5 g, 8.0 mmol). The reaction mixture was subjected refluxed for 4 hours and then stirred at room temperature for 20 hours. Triethylamine (2.5 ml) was added and the mixture was stirred for 30 minutes and evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel, twice, using 1) methylene chloride / methanol (95: 5) and 2) heptane / isopropyl ether (1: 5) as eluent, yielded 0.2 g (8%). %) of the title compound. XH NMR (300 MHz, CDC13): d 1.25 (t, 3H), 1.4 (t, 3H), 2.4 (s, 3H), 2.65-2.8 (m, 5H), 4.35 (d, 2H), 4.45 (q, 2H), 5.15 (t, 1H), 6.25 (d, 1H), 6.85 ( 5, 1H), 7.05-7.2 (m, 3H), 7.35 (d, 1H). Ex empl o 2. 4 Synthesis of ethyl 8-amino-3,6-dimethylimidazo [1, 2- 15 a] pyridine-2-carboxylate A solution of 2,3-diamino-5-methylpyridine (2.3 g, 19 mmol ) and 3-bromo-2-oxobutyric acid ethyl ester (4.3 g, 21 mmol) in ethanol (25 ml) was refluxed for 20 hours. Sodium carbonate (2.6 g, 25 mmol) and the mixture was filtered and the solids were washed with ethanol. The filtrate and washings were combined and the solvents were evaporated under reduced pressure. The residue was dissolved in methylene chloride, washed twice with a sodium carbonate solution and twice with water.

The organic phase was separated, dried (Na 2 SO 4) and evaporated ¿^ Ij ^^^^ j ^^^^^^^^^ ¡^ ¿^ ^^^^^^^^^^^^^ * reduced pressure. purification of the residue by column chromatography on silica gel using methylene chloride / methanol (9: 1) as eluent, afforded 1.3 g (30%) of the title compound as an oil. XH NMR (300 MHz, CDC13): d 1.4 (t, 3H), 2.25 (s, 3H), 2.7 (s, 3H), 4.45 (q, 2H), 4.75 (bs, 2H), 6.2 (s, 1H), 7.1 (s, 1H). Example 2. 5 Synthesis of ethyl 8- (2,6-dimethylbenzylamino) -3,6-dimethylimidazo [1,2- a] -pyridine-2-carboxylate 8-amino-3,6-dimethylimidazo [ 1, 2-a] pyridine-2-carboxylic acid ethyl ester (1.3 g, 5.6 mmol), 2,6-dimethylbenzyl chloride (0.9 g, 6.2 mmol), potassium carbonate (1.5 g, 11 mmol) and sodium iodide (0.1 g, 0.6 mmol) to acetonitrile (15 ml) and the mixture was refluxed for 20 hours. The solvent was evaporated under reduced pressure. The residue was dissolved in methylene chloride, washed twice with water and the organic phase was separated, dried (Na2SO4) and evaporated under reduced pressure. Purification of the residue by column chromatography on silica gel using heptane / ethyl acetate (2: 1) as eluent afforded 0.9 g (47%) of the title compound as an oil. X H NMR (300 MHz, CDCl 3): d 1.35 (t, 3H), 2.4 (s, ^^^^^^^, ^ .._ f, "^ fe ^^^^^^^^^ v ,, .. ^ 3H), 2.45 (s, 6H), 2.7 (s, 3H), 4.35 ( d, 2H), 4.4 (q, 2H), 5.05 (t, 1H), 6.1 (s, 1H), 7.05-7.2 (, 4H). Example 2. 6 Synthesis of diethyl 8-aminoimidazo [1,2-a] pyridine-2,3-dicarboxylate A solution of 2,3-diaminopyridine (13.1 g, 0.12 mol), 2-bromo-3-diethyl ester oxosuccinic (31 g, 0.12 mol) and sodium carbonate (13.2 g, 0.12 mol) in 1,2-dimethoxyethane (200 ml) was refluxed for 20 hours. The solvent was evaporated under reduced pressure and the residue was suspended in methylene chloride and filtered through silica gel. The filtrate was evaporated under reduced pressure to obtain 10.9 g (33%) of the title compound as an oil. XH NMR (300 MHz, CD30D): d 1.5 (t, 6H), 4.5 (q, 4H), 7.15 (d, 1H), 7.3 (t, 1H), 8.75 (d, 1H). Example 2. 7 Synthesis of diethyl 8- (2,6-dimethylbenzylamino) -imidazo [1,2- a] pyridine-2,3-dicarboxylate. 8-aminoimidazo [1,2-a] pyridine-2, 3 was added. diethyldicarboxylate (2.8 g, 10 mmol), 2,6-dimethylbenzyl chloride (1.9 g, 12 mmol), potassium carbonate (2.0 g, 15 mmol) and sodium iodide (0.22 g, 1.5 mmol), a acetonitrile (100 ml) and the mixture was refluxed for 20 hours. Methylene chloride was added to the cold reaction mixture and washed with water. The organic phase was separated, dried (Na2SO4) and evaporated under reduced pressure. Purification of the residue by silica gel column chromatography using methylene chloride 5 as eluent afforded 2.5 g (63%) of the title compound. H NMR (300 MHz, CDC13): d 1.3-1.45 (m, 6H), 2.35 (s, 6H), 4.3 (d, 2H), 4.35-4.45 (m, 4H), 5.05 (t, 1H), 6.45 (d, 1H), 6.95-7.15 (m, 4H), 8.55 (d, 1H). Example 2. 8 Synthesis of 8- (2,6-dimethylbenzylamino) -2- chloromethyl-3-methylimidazo [1,2- a] pyridine To a solution of 8- (2,6-dimethylbenzylamino) -2-hydroxymethyl- 3-methylimidazo [1,2-a] pyridine (1.0 g, 3.4 15 mmol) in methylene chloride (50 ml), thionyl chloride (0.5 g, 3.4 mmol) dissolved in methylene chloride (10 ml) was added dropwise. ml) at 5 ° C. The reaction mixture was stirred for 2 hours at 5 ° C. The mixture was washed with a saturated bicarbonate solution, the organic phase was separated, dried (Na2SO4) and evaporated under reduced pressure, to obtain 1.0 g (93%) of the title compound. * H NMR (300 MHz, CDC13): d 2.4 (s, 6H), 2.5 (s, 3H), 4.35 (d, 2H), 4.75 (s, 2H), 4.9 (bs, 1H), 6.25 (d, 1H), 6.8 (t, 1H), 7.05-7.15 (m, 3H), 7.25 (d, 1H).

"^^^^^^^^^^^^^^^^^^^^^^ BIOLOGICAL TESTING * * * 1. In vitro experiments Inhibition of acid secretion in Isolated rabbit gastric glands The inhibitory effect on in vi tro acid secretion was measured in isolated rabbit gastric glands, in the manner described by Berglindh et al (1976) Acta Physiol. Scand., 97, 401-414. of the activity of i, K-ATPase Membrane vesicles (2.5 to 5 μg) were incubated for 15 minutes at + 37 ° C in 18 mM Pipes / Tris buffer pH 7.4, containing 2 mM MgCl 2, 10 mM KCl and ATP 2 mM ATPase activity was estimated in the form of inorganic phosphate released from ATP, in the manner described by LeBel et al (1978) Anal Biochem 85, 86-89 2. In vivo experiments Inhibitory effect of Acid secretion in female rats Female rats of the Sprague-Dawly breed were used, these were cannulated in the stomach (lumen) and in the upper part of the duodenum to collect the as gastric secretions and for the administration of test substances, respectively. A recovery period of 14 days was allowed after the surgery, before starting the test.

Before performing the secretory tests, the animals were deprived of food but not of water for 20 hours. The stomach was washed repeatedly through the gastric cannula with running water (+ 37 ° C) and with 6 ml of Ringer-Glucose administered subcutaneously. The secretion of acid was stimulated by an infusion for 2.5-4 hours (1.2 ml / h, subcutaneously) of pentagastrin and carbacol (20 and 110 nmol / kg-h, respectively), during which time the gastric secretions were collected in fractions of 30 minutes. The test substances or the vehicle were administered either 60 minutes after the stimulation started (intravenous and intraduodenal administration, 1 ml / kg) or 2 hours before starting the stimulation (oral dose, 5 ml / kg, closed gastric cannula). The time interval between dosing and stimulation can be increased in order to study the duration of the action. Samples of gastric juice were titrated to pH 7.0 with NaOH, 0.1M, and the acid output was calculated as the product of the titration volume by concentration. Other calculations were based on the average responses of groups of 4 to 6 rats. In the case of administration during stimulation, the exit of acid during periods subsequent to the administration of the test substance or vehicle, was expressed as fractionated responses, establishing 1.0 acid output in the period of 30 minutes preceding the administration. Percent inhibition was calculated from the fractional responses induced by the test compound and the vehicle. In the case of administration prior to stimulation, the percentage inhibition was calculated directly from the acid output recorded after the test compound and the vehicle. Bioavailability in rats 0 Adult rats of the Sprague-Dawley breed were used. One to three days before the experiments, all rats were prepared by cannulation of the left carotid artery under anesthesia. The rats used for intravenous experiments were also cannulated in the jugular vein (Popovic (1960) J. Appl. Physiol. 15, 727-728). The cannulas were exteriorized by the nape. Blood samples (from 0.1 to 0.4 g) were taken repeatedly from the carotid artery at intervals of 0 to 5.5 hours after the dose administered. The samples were frozen until analysis of the test compound was carried out. Bioavailability was evaluated by calculating the quotient between the area under the blood curve (ABC) / area 5 under the plasma concentration curve after (i) ^^^ t ^^^^^^^^^^^^^^^^^^^^^^ intraduodenal administration (id) or for oral administration (po) and (ii) intravenous administration (iv), in the rats or dogs, respectively. The area under the curve (ABC) of blood concentration versus time was determined by the trapezoidal rule log / linear and extrapolated to infinity by dividing the last blood concentration determined between the elimination rate constant in the terminal phase. Systemic bioavailability (% F) after 10 intraduodenal or oral administration, was calculated as follows * (%) F = (ABC (po or id) / ABC (iv)) x 100. Inhibition of gastric acid secretion and bioavailability in conscious dogs 15 Labrador Retriever dogs were used or Harrier, of both sexes. To these were placed duodenal fistulas for the administration of test or vehicle compounds and a cannulated gastric fistula or in the Heidenhaim pouch for the collection of gastric secretion. Prior to the secretory tests, the animals were fasted for approximately 18 hours, but were allowed to drink water freely. The secretion of gastric acid was stimulated for up to 6.5 hours by an infusion of histamine dihydrochloride (12 ml / h) to a H¡g 8g ± ----- ^ - a¡ ^^^^ ÉS ^^^^^^^^^^ a ^^^^^^ dose that produced approximately 80% of the individual maximum secretory response , and the gastric juice was collected in consecutive fractions of 30 minutes. The substance or vehicle was administered orally, i.d. or i.v., from 1 to 5 1.5 hours after initiating the histamine infusion, in a volume of 0.5 ml / kg of body weight. In the case of oral administration, it should be noted that the test compound was administered in the main stomach secreting acid from the Heidenhaim pouch in dogs. 10 The acidity of the gastric juice samples was determined by titration up to pH 7.0 and the acid output was calculated. The acid exit in the collection periods after the administration of the test substance or the vehicle was expressed as fractionated responses, establishing the acid exit in the fraction preceding the administration in 1.0. Percent inhibition was calculated from the fractional responses induced by the test compound and the vehicle. The blood samples for the analysis of the concentration of the test compound in the plasma were taken at intervals of up to 4 hours after the dose. The plasma was separated and frozen within a period of 30 minutes after collection and subsequently analyzed. The systemic bioavailability (% F) after the ~ í 5"* ** *** ** - * - * - * - 3 &i ^ ^ üHf ^ 62¡? iUá ~ ai r .. oral administration or i.d., was calculated in the manner previously described in the model in rats. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (16)

1. CLAIMS Having described the invention as an antecedent, the content of the following claims is claimed as property: 1. A compound of the formula I or a pharmaceutically acceptable salt thereof, characterized in that R1 is (a) H, (b) CH3, or (c) CH2OH, R2 is alkyl of 1 to 6 carbon atoms; R3 is alkyl of 1 to 6 carbon atoms; R4 is (a) H, or (b) halogen; R5 is (a) H, or
2. A ^ ^ ^ ^ ^ ^ a ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ R6 is' "* - (a) H, (b) C 1 -C 6 alkylcarbonyl, (C) cycloalkylcarbonyl of 3 to 7 carbon atoms, in which the cycloalkyl group is optionally substituted with one or more substituents which are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), (d) aryl-alkylcarbonyl of 1 to 6 carbon atoms, in which the aryl radical represents a phenyl, pyridyl, thienyl or furanyl group, optionally substituted with one or more substituents which are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -C00- (alkyl of 1 to 6 carbon atoms), (e) alkoxy of 1 to 6 carbon atoms-alkylcarbonyl of 1 to 6 carbon atoms, (f) alkoxycarbonyl 1 to 6 carbon atoms, (g) arylcarbonyl in which the aryl group represents phenyl, pipdoyl, thienyl or furanyl, optionally substituted with one or more substituents which are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms carbon, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), (h) cycloalkyl of 3 to 7 carbon atoms-alkylcarbonyl of 1 to 6 carbon atoms, in which the cycloalkyl group is optionally substituted with one or more substituents which are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), (i) C 1-6 alkoxy-alkoxycarbonyl having 1 to 6 carbon atoms, (j) C 1-6 alkoxy-alkoxy 1 to 6 carbon atoms-alkylcarbonyl of 1 to 6 carbon atoms, (k) a carbamoyl group of the formula wherein R7, R8 are the same or different and represent H, or alkyl of 1 to 6 carbon atoms, (1) R9- (alkylcarbonyl of 1 to 6 carbon atoms), wherein R9 is HOC = 0-, alkyl ( of 1 to 6 carbon atoms) -O- C = 0-, or an amino group of the formula - ^^^^^ z¿a¡ i ^ where R7, R8 are the same or different and represent H or alkyl of 1 to 6 carbon atoms, (m) R9-alkylcarbonyl (from 1 to 6 carbon atoms) ) hydroxylated, (n) R9-alkenylcarbonyl of 1 to 6 carbon atoms, X is (a) NH, or 10 (b) O. 2. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized because R1 is 15 (a) CH3, or (b) CH2OH, R2 is alkyl of 1 to 6 carbon atoms; R3 is alkyl of 1 to 6 carbon atoms; R "is 20 (a) H, or (b) halogen, R5 is (a) H, or (b) all-alkyl of 1 to 6 carbon atoms;
3. R6 is (a) alkylcarbonyl of 1 to 6 carbon atoms, (b) cycloalkylcarbonyl of 3 to 7 carbon atoms, in which the cycloalkyl group is optionally substituted with one or more substituents that are selected from the group consisting of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), (c) Aryl-alkylcarbonyl of 1 to 6 carbon atoms, in which the aryl radical represents a phenyl, pyridyl, thienyl or furanyl group, optionally substituted with one or more substituents which are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), (d) alkoxy of 1 to 6 carbon atoms- alkylcarbonyl of 1 to 6 carbon atoms, (e) alkoxycarbonyl of 1 to 6 carbon atoms, (f) arylcarbonyl in which the aryl group represents phenyl, pyridyl, thienyl or furanyl, optionally substituted c on one or more substituents that are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms), (g ) cycloalkyl of 3 to 7 carbon atoms alkylcarbonyl of 1 to 6 carbon atoms, in which the. The cycloalkyl group is optionally substituted with one or more substituents which are selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -COOH or -COO- (alkyl of 1 to 6 carbon atoms). carbon), (h) alkoxy of 1 to 6 carbon atoms-alkoxycarbonyl of 1 to 6 carbon atoms, (i) alkoxy of 1 to 6 carbon atoms-alkoxy of 1 to 6 carbon atoms-alkylcarbonyl of 1 to 6 carbon atoms, (j) a carbamoyl group of the formula or - ^ N Rβ wherein R7, R8 are the same or different and represent H, or alkyl of 1 to 6 carbon atoms, (k) R9- (alkylcarbonyl of 1 to 6 carbon atoms), wherein R9 is HOC = 0-, alkyl (of 1 to 6 carbon atoms) -OC = 0-, or an amino group of the formula fr * pwPtittt Éatfü where R7, R8 are the same or different and represent H or alkyl of 1 to 6 carbon atoms, (1) R9-alkylcarbonyl (1 to 6 carbon atoms) hydroxylated, (m) R9-alkenylcarbonyl of 1 to 6 carbon atoms, X is (a) NH, or (b) O. 3. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that R1 is CH3 or CH2OH; R2 is CH3 or CH2CH3; R3 is CH3 or CH2CH3; R4 is H, Br, Cl or F; R5 is H or CH3, [8- (2,6-dimethylbenzylamino) -3-methyloxy [1, 2-a] pyridin-2-yl] -methyl acetate; [8- (2,6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] pyridin-2-yl] -methyl ethylcarbonate; [8- (2,6-Dimethylbenzylamino) -3-methylimidazo [1, 2-a] pipdin-2-yl] -methyl N-N-dimethylcarbamate; 3-ethylmalonate of 1- [[8- (2,6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] pyridin-2-yl] -methyl]; 4- [[8- (2,6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] pyridin-2-yl] -methoxy] -4-oxubutanoic acid;
4. 4- [[8- (2-ethyl-6-methylbenzylamino) -3-methylimidazo [1, 2-a] pyridin-2-yl] -methoxy] -4-oxobutanoic acid;
5. 5- [[8- (2,
6. 6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] -pyridin-2-yl] -methoxy] -5-oxopentanoic acid; [8- (2,6-dimethylbenzylamino) -3-methylimidazo [1, 2-a] -pyridin-2-yl] -methyl-2- (dimethylamino) -acetate; or a pharmaceutically acceptable salt thereof. . 8- (2,6-dimethylbenzylamino) -2,3-dihydroxy-methylimidazo [1,2-a] pyridine; 8- (2-ethyl-6-methylbenzylamino) -2-hydroxymethyl-3-methyloxyzo [1,2-a] pyridine; 8- (2,6-dimethylbenzylamino) -2-hydroxymethyl-3-methylimidazo [1,2-a] pyridine; 8- (2,6-dimethylbenzylamino) -3,6-dimethyl-2-hydroxymethylimidazo [1,2-a] pyridine; or a pharmaceutically acceptable salt thereof. 5. A product characterized in that it contains a compound according to any of claims 1 to 4 and at least one antimicrobial agent in the form of a combined preparation, for simultaneous administration, separately or sequentially, in the prevention or treatment of gastrointestinal inflammatory diseases . 6. A product characterized in that it contains a compound according to any of claims 1 to 4 and at least one proton pump inhibitor, in the form of a combined preparation, for simultaneous administration, separately or sequentially, in the prevention or treatment of Gastrointestinal inflammatory diseases. 7. A process for the preparation of a compound according to any of claims 1 to 4, characterized in that it comprises: a) reacting a compound of the general formula III wherein Xi is NH2 or OH and R5 is as defined for formula I, with compounds of general formula IV wherein Z is a leaving group, Y is a lower alkyl group and R is H, CH3 or an ester group, in an inert solvent under standard conditions, to obtain a compound of formula II ^^ jtogÉM b) reacting a compound of formula V where R2, R3 and R4 are as defined for the formula I and Zi is a leaving group, with a compound of the formula II under standard conditions, in an inert solvent, with or without a base, to obtain a compound of the formula VI wherein R, R, R 'R and X are as defined for formula I, Y is a lower alkyl group and R is H, CH3 or an ester group, c) reducing a compound of general formula VI, in a inert solvent to obtain a compound of the general formula I wherein R6 is H, e > ^ i ** ^ ^ ~ * ~ -,. ~ ^^^ 7 ^^^^. T. ^^^ .. ^ ^^^ k ^^^ d) introducing the substituent R6 of the formula I (R6? H) by standard acylation procedures, reacting a compound of the formula I wherein R6 is H, with the acid, acid halide or anhydride of R6 (R6 5 ? H). 8. A process for the preparation of a compound according to any of claims 1 to 4, characterized in that it comprises: a) halogenating the hydroxymethyl group of a compound of the formula I wherein R6 is H, to obtain the corresponding group Halomethyl of formula VII, by standard methods, b) enter R6 of the formula I (R6? H) By reacting a compound of the formula VII with the corresponding acid of R6 (R6? H), under standard conditions. 9. A compound according to any of claims 1 to 4, characterized in that it is used in therapy. 10. A pharmaceutical formulation characterized in that it contains a compound according to any of claims 1 to 4 as an active ingredient, in combination with a pharmaceutically acceptable diluent or carrier. 11. The use of a compound according to any of claims 1 to 4 for the manufacture of a medicament for the inhibition of gastric acid secretion. 12. The use of a compound according to any of claims 1 to 4 for the manufacture of a medicament for the treatment of gastrointestinal inflammatory diseases. The use of a compound according to any of claims 1 to 4 for the manufacture of a medicament for the treatment or prophylaxis of disorders including Helicobacter pylori infections of the human gastric mucosa, characterized in that the compound is adapted to be administered in combination with at least one antimicrobial agent. 14. A pharmaceutical formulation for use in the inhibition of gastric acid secretion, characterized in that the active ingredient is a compound according to any of claims 1 to 4. 15. A pharmaceutical formulation for use in the treatment of gastrointestinal inflammatory diseases, characterized because the active ingredient is a compound according to any of claims 1 to 4. 16. A pharmaceutical formulation for use in the treatment or prophylaxis of disorders including Helicobacter pyl ori infections of the human gastric mucosa, characterized in that the active ingredient is a compound according to any one of claims 1 to 4, in combination with at least one antimicrobial agent.