MXPA00010231A - Imidazo pyridine derivatives which inhibit gastric acid secretion - Google Patents

Abstract

The present invention relates to imidazo pyridine derivatives of formula (I), in which the phenyl moiety is substituted, and in which the imidazo pyridine moiety is substituted with carboxamide group in 6-position, which inhibit exogenously or endogenously stimulated gastric acid secretion and thus can be used in the prevention and treatment of gastrointestinal inflammatory diseases.

Description

DERIVATIVES OF MIDAZOPIRIDINE THAT INHIBIT THE SECRE ION OF GASTRIC ACID TECHNICAL FIELD The invention relates to novel compounds, and pharmaceutically acceptable salts thereof, which inhibit the secretion of exogenously or endogenously stimulated gastric acid and thus can be used in the prevention and treatment of diseases. inflammatory bowel In additional aspects, the invention relates to the compounds of the invention for use in therapy; to the processes for the preparation of such new compounds; to pharmaceutical compositions containing at least one compound of the invention or a pharmaceutically acceptable salt of the iftisms, as an active ingredient; and to the use of active ingredients in the manufacture of medicines for the medical use indicated above. The invention also relates to novel intermediates for the preparation of novel compounds.

Ref: 123829 BACKGROUND OF THE INVENTION Substituted imidazo [1, 2-a] pyridines, useful in the treatment of peptic ulcer diseases, are known in the art, for example from EP-B-0033094 and US 4,450,164 (Schering Corporation); of EP-B-0204285 and US 4,725,601 (Fujisawa Pharmaceutical Co.); and from publications by JJ Kaminski et al in Journal of Medical Chemistry (vol 28, 876-892; 1985; vol 30, 2031-2046; 1987; vol 30, 2047-2051 1987, vol 32, 1686). 1700, 1989, and vol 34, 533-541, 1991). For a review of 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 It has surprisingly been found that the compounds of the formula I, which are imidazopyridine derivatives. in which the phenyl portion is substituted, and in which the imidazopyridine portion is substituted with a carboxamide group in the 6-position, they are particularly effective as inhibitors of gastrointestinal H +, K + -ATPase and therefore are inhibitors of the secretion of Gastric acid. The carboxamide group in the 6-position is optionally selected to give the compounds of Formula I of a molecular weight < 600. In one aspect, the invention thus relates to the compounds of the general Formula I or a pharmaceutically acceptable salt thereof, wherein R1 is (a) H, (b) CH3, or (c) CH2OH; R2 is (a) CH3, or (b) CH2CH3; R3 is (a) H (b) alkyl of 1 to 6 carbon atoms (c) alkyl of 1 to 6 hydroxy carbon atoms, or (d) halogen; R 4 is (a) H, (b) alkyl of 1 to 6 carbon atoms, (c) alkyl of 1 to 6 carbon atoms hydroxylated, or (d) halogen; R5 is (a) H, or (b) halogen; R6 and R7 are independently selected substituents, which comprise carbon, hydrogen, nitrogen, oxygen, sulfur, selenium, phosphorus and halogen atoms, which give compounds of Formula I of molecular weight < ^ 600, with the proviso that at least one of R6 and R7 can not be hydrogen, alkyl of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms hydroxylated, or alkyl of 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms, and X is (a) NH, or (b) 0. As used herein, the term "alkyl of 1 to 6 carbon atoms" denotes a linear or branched alkyl group which has from 1 to 6 carbon atoms. Examples of said alkyl of 1 to 6 carbon atoms include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl and straight and branched chain pentyl and hexyl. The term "halogen" includes fluorine, chlorine, bromine and iodine. The substituents R6 and R7 are defined as independently selected substituents, which comprise the carbon, hydrogen, nitrogen, oxygen, sulfur, selenium, phosphorus or halogen atoms, which give compounds of Formula I with a molecular weight < 600, which is a definition easily understood by a person of skill in the art.

Examples of substituents that fall within the scope of this invention include, but are not limited to, a) hydrogen, b) alkyl of 1 to 6 carbon atoms, c) alkyl of 1 to 6 hydroxy carbon atoms, d) alkyl from 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms, e) alkenyl of 2 to 6 carbon atoms, f) alkynyl of 2 to 6 carbon atoms, g) alkyl of 1 to 6 carbon atoms halogenated, h) cycloalkyl of 3 to 8 carbon atoms, i) alkyl of 1 to 6 carbon atoms substituted with cycloalkyl, j) aryl, in which the aryl group represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3, OH, nitro, amino, (alkyl of 1 to 6 carbon atoms) - NH-, (C 1-6 alkyl) -N-, or CN or NH 2 S0 2, k) alkyl of 1 to 6 carbon atoms aryl substituted rbonon, in which the aryl group represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, nitro, amino- (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2-N-, CN or NH2S02, 1) R8- (alkyl of 1 to 6 carbon atoms) -, wherein R8 is NH2C = 0-, (alkyl of 1 to 6 carbon atoms) -NHC = 0-, (alkyl of 1 to 6 carbon atoms) 2NC = 0 -, (alkyl of 1 to 6 carbon atoms) -OOC-, NH2S02-, (alkyl of 1 to 6 carbon atoms) -S02-NH-, ArS02NH-, cyano, (alkyl of 1 to 6 carbon atoms) -CO-NH-, (alkyl of 1 to 6 carbon atoms) -OOCNH-, (alkyl of 1 to 6 carbon atoms) -O-, (alkyl of 7 to 12 carbon atoms-O- (alkyl of 1 to 6 carbon atoms) -SO-, (alkyl of 1 to 6 carbon atoms) -S-, (alkyl of 1 to 6 carbon atoms) -S02-, ( alkyl of 1 to 6 carbon atoms) -C = 0-, NH2-, (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2N-, ArCONH-, Ar ( alkyl of 1 to 6 carbon atoms) CONH, ArNHS02-, (Ar) 2-N-S02-, (alkyl of 1 to 6 carbon atoms) -NHS02-, ArS-, ArSO-, ArS02-, ArC = 0 -, NH2CONH- (C 1 to C 6 alkyl) -NHCONH-, (C 1-6 alkyl) 2-NCONH-, ArNHCONH-, Ar-O-, Ar-NH-, Ar (alkyl) from 1 to 6 carbon atoms) N-, (C 1-6 alkyl) 2NS02-, (hydroxylated C 1-6 alkyl) -0- or morpholinyl; wherein Ar represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH , CN, nitro, amino, (alkyl of 1 to 6 carbon atoms) -NH-, or (alkyl of 1 to 6 carbon atoms) 2N-. m) 7 to 12 carbon atoms, n) OH, 0- (alkyl of 1 to 6 carbon atoms), or 0- (alkyl of 1 to 6 hydroxy carbon atoms), H R9-N, 10 > , and wherein R5 R are R10-N independently hydrogen or alkyl of 1 to 6 carbon atoms, p) R11- (alkyl of 1 to 6 carbon atoms) -COO- (alkyl of 1 to 6 carbon atoms) - wherein R11 is HOOC-, (alkyl of 1 to 6 carbon atoms) -OOC- or an aminocarbonyl group with the formula wherein R12, R13 are the same or different, hydrogen, or alkyl of 1 to 6 carbon atoms. R6 and R7 * together with the nitrogen atom to which they are attached, form a saturated or unsaturated ring optionally containing one or more additional heteroatoms (for example morpholine, piperazine, pyrrolidine, piperidine), optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, nitro, amino (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) ) 2-N-, CN, NH2S02, phenyl, NH2CO-, (alkyl of 1 to 6 carbon atoms) -CO-, the ring can be fused with an aromatic ring (such as tetrahydroquinoline); Pure enantiomers, racemic mixtures and unequal mixtures of two enantiomers are within the scope of the invention. It should be understood that all possible diastereomeric forms (pure enantiomers, racemic mixtures and unequal mixtures of two enantiomers) are within the scope of the invention. Also included in the invention are derivatives of the compounds of the formula I which have the biological function of the compounds of the formula I, such as prodrugs. It may also be appreciated by those skilled in the art, although derivatives of the compounds of formula I may not possess pharmacological activity as such, which may be administered parenterally or orally, and thereafter metabolized in the body to form the compounds of the invention that are pharmacologically active. Such derivatives can therefore be described as "prodrugs". All prodrugs of the compounds of formula I are included within the scope of the invention. Depending on the process conditions, the final products of formula I are obtained either in neutral or salt form. The free base and the salts of these final products are within the scope of the invention. The acid addition salts of the novel compounds can, in a manner known per se, be transformed into the free base using basic agents such as alkali 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, such acids which form the pharmaceutically acceptable salts are preferably used. Examples of such acids are hydrohalogenic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfonic acids, such as formic acid, acetic acid, propionic acid, succinic acid , glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, as.corbic acid, maleic acid, hydroxymeleic acid, pyruvic acid, p-hydroxybenzoic acid, embonic acid, methanesulfonic acid, ethanesulfonic acid, hydroxyethane sulfonic acid, halogenobenzenesulfonic acid, toluenesulfonic acid or naphthalenesulfonic acid. Preferred compounds according to the invention are those of Formula I where Ra is CH 3, or CH 2 OH; R2 is CH3 or CH2CH3; R3 is CH3 or CH2CH3; R4 is CH3 or CH2CH3; R5 is H, Br, Cl, or F; R6 and R7 are independently (with the proviso that at least one of R6 and R7 can not be hydrogen, alkyl of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms hydroxylated, or alkyl of 1 to 6 carbon atoms. carbon substituted with alkoxy of 1 to 6 carbon atoms): a) hydrogen, b) alkyl of 1 to 6 carbon atoms, c) alkyl of 1 to 6 hydroxy carbon atoms, d) alkyl of 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms, e) alkenyl of 2 to 6 carbon atoms, f) alkynyl of 2 to 6 carbon atoms, g) alkyl of 1 to 6 carbon atoms halogenated, h) cycloalkyl of 3 at 8 carbon atoms, i) alkyl of 1 to 6 carbon atoms substituted with cycloalkyl, j) aryl, in which the aryl group represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms carbon, CF3, OH, nitro, amino, (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2-N-, or CN or NH2S02, k) alkyl of 1 to 6 carbon atoms substituted with aryl, in which the aryl group represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy from 1 to 6 carbon atoms, CF3, OH, nitro, amino- (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2-N-, CN or NH2S02, 1) R8- (alkyl of 1 to 6 carbon atoms) -, where R8 is NH2C = 0-, (alkyl of 1 to 6 carbon atoms) -NHC = 0-, (alkyl of 1 to 6 carbon atoms) 2NC = 0-, (alkyl of 1 to 6 carbon atoms) -OOC-, NH2S02-, (alkyl of 1 to 6 carbon atoms) -S02-NH-, ArS02NH-, cyano, (alkyl of 1 to 6 carbon atoms) -CO-NH-, (alkyl of 1 to 6 carbon atoms) -OOCNH-, (alkyl of 1 to 6 carbon atoms) -O-, (alkyl of 7 to 12 carbon atoms-O- (alkyl of 1 to 6 carbon atoms) -SO-, (C 1-6 alkyl) -S-, (C 1-6 alkyl) -S02-, (C 1-6 alkyl) -C = 0-, NH 2- , (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2N-, ArCONH-, Ar (alkyl of 1 to 6 carbon atoms) CONH, ArNHS02-, (Ar) 2-N-S02-, (alkyl of 1 to 6 carbon atoms) -NHS02-, ArS-, ArSO-, ArS02-, ArC = 0-, NH2CONH - (alkyl of 1 to 6 carbon atoms) -NHCONH-, (alkyl of 1 to 6 carbon atoms) 2-NCONH-, ArNHCONH-, (alkyl of 1 to 6 carbon atoms) 2-N-S02-, Ar-O-, Ar-NH-, Ar (C 1-6 -alkyl) N-, (C 1-6 -alkyl) 2NS02-, (C 1-6 -alkylated hydroxylated) -O - or morpholinyl; wherein Ar represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH , CN, nitro, amino, (alkyl of 1 to 6 carbon atoms) -NH-, or (alkyl of 1 to 6 carbon atoms) 2N-. m) 7 to 12 carbon atoms, n) OH, 0- (alkyl of 1 to 6 carbon atoms), or 0- (alkyl of 1 to 6 hydroxy carbon atoms), H R9-N independently hydrogen or alkyl of 1 to 6 carbon atoms, p) R11- (alkyl of 6 carbon atoms) -COO- (alkyl of 1 to 6 carbon atoms) -where R11 is HOOC-, (alkyl of 1) to 6 carbon atoms) -OOC- or an aminocarbonyl group with the formula wherein R12, R13 are the same or different, hydrogen, or alkyl of 1 to 6 carbon atoms. R6 YR together with the nitrogen atom to which they are attached, form a saturated or unsaturated ring optionally containing one or more additional heteroatoms (for example morpholine, piperazine, pyrrolidine, piperidine), optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3, OH, nitro, amino (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2 -N-, CN, NH2S02, phenyl, NH2C0-, (alkyl of 1 to 6 carbon atoms) -CO-, the ring can be fused with an aromatic ring (such as tetrahydroquinoline); The most preferred compounds according to the invention are those of Formula I wherein R 1 is CH 3 or CH 2 OH; R2 is CH3, R3 is CH3 or CH2CH3; R4 is CH3 or CH2CH3; R5 is H, Br, Cl, or F; R6 and R7 are independently (with the proviso that at least one of R6 and R7 can not be H, alkyl of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms hydroxylated or alkyl of 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms): a). hydrogen b) alkyl of 1 to 6 carbon atoms, c) alkyl of 1 to 6 carbon atoms hydroxylated, d) alkyl of 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms, e) alkyl of 1 to 6 halogenated carbon atoms, f) aryl, in which the aryl represents phenyl, pyridyl, imidazolyl, indolyl, or naphthyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy 1 to 6 carbon atoms, CF3, OH, (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2-N-, or CN, g) alkyl of 1 to 6 carbon atoms substituted with aryl, in which the aryl group represents phenyl, pyridyl, imidazolyl, indolyl, 0 naphthyl, optionally substituted with one or more substituents selected from halogen, alkyl 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, or OH, h) R8- (alkyl of 1 to 6 carbon atoms) -, wherein R8 is NH2C = 0-, (alkyl of 1 to 6 carbon atoms) -NHC = 0-, (alkyl of 1 to 6 carbon atoms) 2NC = 0-, (alkyl of 1 to 6 carbon atoms) -OOC-, cyano, (alkyl of 1 to 6 atoms) carbon) -CO-NH-, (alkyl of 1 to 6 carbon atoms) -OOCNH-, (alkyl of 1 to 6 carbon atoms) -0-, (alkyl of 7 to 12 carbon atoms) -0- (alkyl of 1 to 6 carbon atoms) -SO-, (C 1-6 alkyl-S-, (C 1-6 alkyl) -C = 0-, ArCONH-, Ar (alkyl) 1 to 6 carbon atoms) CONH, ArC = 0-, NH2CONH- (alkyl of 1 to 6 carbon atoms) -NHCONH-, (alkyl of 1 to 6 carbon atoms) 2NC0NH-, ArNHCONH-, (alkyl of 1 at 6 hydroxy carbon atoms) -0- or morpholinyl, wherein Ar represents phenyl, pyridyl, imidazolyl, indolyl, or naphthyl optionally substituted with one or more substituents selected from halogen, alkyl d 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF 3, OH, CN, i) C 7 -C 12 alkyl, j) OH, k) R 11 - (C 1-6 alkyl) carbon) -COO- (alkyl of 1 to 6 carbon atoms) -where R11 is HOOC-, or (alkyl of 1 to 6 carbon atoms) -OOC R6 and R7, together with the nitrogen atom to which they are attached , form a saturated or unsaturated ring optionally containing one or more heteroatoms (for example morpholine, piperazine, pyrrolidine, piperidine), optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, nitro, amino, CN, NH2S02, phenyl, NH2C0-, (alkyl of 1 to 6 carbon atoms) -CO-, the ring can be fused with an aromatic ring (such as tetrahydroquinoline). The most preferred compounds according to the invention are: • 2,3-dimethyl-8- (2-ethyl-6-methylbenzylamino) -6- (morpholinecarbonyl) -imidazo [1,2-a] pyridine • N- (4 -ethoxyphenyl) -8- (2-ethyl-6-methylbenzylamino) -2, 3-dimethylimidazo [1,2-a) pyridine-6-carboxamide • N- [2- (dimethylamino) -2-oxoethyl] -8- (2-ethyl-6-methylbenzylamino) -N, 2, 3-trimethylimidazo [1,2-a) pyridine-6-carboxamide • (8- (2-ethyl-6-methylbenzylamino) -2,3-dimethylimidazo [l , 2-a] pyridin-yl) (4-methylpiperazino) methanone • 1- ((8- (2-eti1-6-methylbenzylamino) -2,3-dimethylimidazo [1,2- a] pyridin-6-yl) carbonyl) -2- (s) -pyrrolidinecarboxamide • 8- (2-ethyl-6-methylbenzylamino) -N-hydroxy-2,3-dimethylimidazo [1,2- a] pyridine-6-carboxamide • (2-ethyl- 6-methylbenzylamino) -N- (2- (2-hydroxyethoxy) ethyl) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide • (8- (2-ethyl-6-methylbenzylamino) -2 , 3-dimethylo idazo [1,2-a] pyridin-6-yl) (3-hydroxy-l-pyrrolidinyl) ethanone • N- (3,4-hydroxyphenethyl) -8- (2-ethyl-6) -methylbenzylamino) -2, 3-dimethylimidazo [1,2-a] pyridine-6-carboxamide • 8- (2-ethyl-6-methylbenzylamino-3- (hydroxymethyl) -2-methyl-6- (morpholinecarbonyl) -imidazo [1,2-a] pyridine • N- ((8- (2-ethyl-6-methylbenzyl) amino) -2,3-dimethylimidazo [1,2- a] pyridin-6-yl) carbonyl) guanidine • acid 4- (2- (((8- (2-ethyl-6-methylbenzylamino) -2,3-dimethylimidazo [1,2- a] pyridin-6-yl) carbonyl) amino) -ethoxy) -4-oxobutanoic acid Preparation The present invention also provides the following process for the manufacture of compounds with the general Formula I. A process for the manufacture of the compounds with the general formula I comprises the following steps: a) The compounds of the Formula II wherein R1, R2, R3, R4, R5 and X are as defined in Formula I, they can be hydrolyzed under standard conditions to the corresponding carboxylic acid to form the corresponding carboxylic acid compounds of Formula III b) Compounds of Formula III wherein R1, R2, R3, R4, R5 and X are as defined in Formula I, can be reacted with the amino compounds of Formula IV where R6 and R7 are as defined for the Formula I, in the presence of a coupling reagent to the corresponding amide compounds of Formula I. The reaction can be carried out in an inert solvent under standard conditions. The present invention also provides the following process for the manufacture of intermediates with General Formula II. A process for the manufacture of the compounds of the general Formula II wherein X is NH, comprises the following steps: a) The compounds of the general Formula V they can be reacted with the amino compounds of the general Formula IV IV wherein R6 and R7 are both hydrogen, to the corresponding amine of Formula VI. The reaction can be carried out under standard conditions in an inert solvent. b) The compounds of the general formula VI can be reacted with ammonia to the compounds of the general formula VII wherein R6 and R7 are both hydrogen. The reactions can be carried out under standard conditions in an inert solvent. c) Compounds of Formula VII can be reduced, for example, by the use of hydrogen and a catalyst such as .Pd / C to the compounds of Formula VIII wherein R6 and R7 are both hydrogen. The reaction can be carried out under standard conditions in an inert solvent. d) The imidazo [1,2-a] pyridine compounds of Formula X can be prepared by the reaction of the compounds of the general Formula VIII with the compounds of the general Formula IX IX wherein R2 is as defined for Formula I and Z is a leaving group such as halogen, mesyl, tosyl and R9 represents hydrogen, CH3 or an ester group such as COOCH3, COOC2H5, etc. The reaction is carried out under standard conditions in an inert solvent such as acetone, acetonitrile, alcohol, dimethylformamide, etc., with or without a base. e) The compounds of Formula X can be reacted with the compounds of Formula XI XI where R3, R4 and R5 are as defined for the Formula I and Y is a leaving group, such as a halide, tosyl or mesyl, to the compounds of Formula XII. wherein R2, R3, R4 and R5 are as defined for Formula I and R6 and R7 are both hydrogen and R9 is hydrogen, CH3 or an ester group such as COOCH3, COOC2H5, etc. It is convenient to conduct this reaction in an inert solvent, for example, acetone, acetonitrile, dimethoxyethane, methanol, ethanol or dimethylformamide with or without a base. The base is for example an alkali metal hydroxide, such as sodium hydroxide and potassium hydroxide, an alkali metal carbonate, such as potassium carbonate and sodium carbonate; or an organic amine, such as triethylamine. f) The reduction of the compounds of the general Formula XII wherein R9 is an ester group for example by the use of lithium borohydride in an inert solvent, such as tetrahydrofuran or diethyl ether, to the compounds of the general Formula I wherein R1 is CH2OH and R6 and R7 are both hydrogen.

Medical use In a further aspect, the invention relates to the compounds of the formula I for use in therapy, in particular for use against gastrointestinal inflammatory diseases. The 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 invention can thus be used for the prevention and treatment of gastrointestinal inflammatory diseases, and gastric acid-related diseases in mammals including man, such as gastritis, gastric ulcer, duodenal ulcer, reflux oesophagitis. and Zollinger-Ellison syndrome. In addition, the compounds can be used for the treatment of other gastrointestinal disorders where the gastric antisecretory effect is desirable, for example in patients with gastrinomas, and in patients with acute upper gastrointestinal bleeding. These can also be used in patients in situations of intensive care, and pre- and post-operatively to prevent aspiration of acid and ulceration by stress or tension. 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 requirement of each patient, the route of administration and the disease. In general, oral and parenteral doses will be in the range of 5 to 1000 mg per day of the active substance.

Pharmaceutical Formulations In a further aspect, the invention relates to pharmaceutical compositions containing at least one compound of the invention, or a pharmaceutically acceptable salt thereof, as an active ingredient. The compounds of the invention can also be used in formulations together with other active ingredients, for example antibiotics such as amoxicillin. For clinical use, the compounds of the invention are formulated in pharmaceutical formulations for oral, rectal, parenteral, or other administration administration. The pharmaceutical formulation contains at least one compound of the invention in combination with one or more pharmaceutically acceptable ingredients. The carrier can be in the form of a solid, semi-solid or liquid diluent, or a capsule. These pharmaceutical preparations are a further objective of the invention. Usually, the amount of active compounds is between 0.1 to 95% by weight of the preparation, preferably between 0.1-20% by weight in preparations for parenteral use and preferably between 0.1 and 50% by weight in preparations for oral administration. In the preparation of pharmaceutical formulations containing a compound of the present invention in the form of unit doses for oral administration, the selected compound can be mixed with ingredients, solid or powder, such as lactose, sucrose, sorbitol, mannitol, starch. , amylopectin, cellulose derivatives, gelatin, or other suitable ingredient, as well as with disintegrating agents and lubricating agents such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylene glycol waxes. The mixture is then processed into pellets or pressed into tablets. Soft gelatin capsules can be prepared with capsules containing a mixture of the active compound or compounds of the invention, vegetable oil, fat, or other suitable vehicle for soft gelatine capsules. Hard gelatin capsules may contain granules of the active compound. Hard gelatine capsules may also contain the active compound in combination with solid powder ingredients, such as lactose, sucrose, sorbitol, mannitol, potato starch, corn starch, amylopectin, cellulose derivatives or gelatin. The dose units for rectal administration can be prepared (i) in the form of suppositories, which contain the active substance mixed with a neutral fat base; (ii) in the form of a rectal gelatin capsule containing the active substance in a mixture with a vegetable oil, paraffin oil or other suitable vehicle for rectal gelatin capsules; (iii) in the form of a ready-to-use microenema; (iv) in the form of an anhydrous microenema formulation to be reconstituted in a suitable solvent just prior to administration. Liquid preparations for oral administration can be prepared in the form of syrups or suspensions, for example 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 agents, flavoring agents, saccharin and carboxymethylcellulose or other thickening agent. Liquid preparations for oral administration may also be prepared in the form of a dry powder to be reconstituted with a suitable solvent before use. Solutions for parenteral administration can be prepared as a solution of a compound of the invention in a pharmaceutically acceptable solvent, preferably in a concentration of 0.1% to 10% by weight. These solutions may also contain stabilizing ingredients and / or buffering ingredients and are supplied in unit doses in the form of ampoules or flasks. Solutions for parenteral administration can also be prepared as an anhydrous preparation to be reconstituted with a suitable solvent extemporaneously before use. The compounds according to the present invention can also be used in formulations, in combination or in combination for simultaneous, separate or sequential use, with other active ingredients, for example for the treatment or prophylaxis of conditions involving infection by Heli cobacter pyl ori of the human gastric mucosa. Other active ingredients such may 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 • 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, separate or sequential use with antacids such as aluminum hydroxide, magnesium carbonate and magnesium hydroxide or alginic acid, or together or in combination for the simultaneous, separate or sequential use with pharmaceuticals that inhibit acid secretion, such as H2 blockers (eg cimetidine, ranitidine), H + / K + -ATPase inhibitors (eg omeprazole, pantoprazole, lansoprazole or rabeprazole) or together in combination for simultaneous, separate or sequential use with gastroprokinetics (eg, cisapride or mosapride).

Intermediaries A further aspect of the invention is the novel intermediate compounds that are useful in the synthesis of the compounds according to the invention. Thus, the invention includes a) a compound of Formula XVIII XVIII wherein R1, R2, R3, R4, R5 and X are as defined for Formula I. b) a compound of Formula VIII VIII wherein R2, R6 and R7 are as defined for Formula I, and R9 is hydrogen, CH3 or an ester group such as COOCH3, COOC2H5, etc .; c) a compound of Formula X wherein R2, R3, R4, R5, R6 and R7 are as defined for Formula I, and R9 is an ester group such as COOCH3, COOC2H5, etc .; EXAMPLES PREPARATION OF THE COMPOUNDS OF THE INVENTION EXAMPLE 1.1 Synthesis of 2,3-dimethyl-8- (2-ethyl-6-methylbenzylamino) -6- (morpholinocarbonyl) -imidazo [1,2-a] pyridine 2,3-Dimethyl-8- (2-ethyl-6-methylbenzylamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.15 g, 0.44 mmol) and o-benzotriazole-1- tetrafluoroborate IL-N, N, N ', N' -tetramethyluronium (TBTU) (0.14 g, 0.44 mmol) were added to 10 ml of methylene chloride. Morpholine (0.12 g, 1.4 mmol) was added and the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was added to a column with silica gel and purified by chromatography using ethyl acetate: methylene chloride (1: 1) as eluent to give 0.12 g (66%) of the desired product.

NMR aH (300 MHz, CDC13): d 1.2 (t, 3H), 2.32 (s, 3H), 2.35 (s, 3H), 2.37 (s, 3H), 2.7 (q, 2H), 3.7 (s, 8H), 4.35 (d, 2H), 4.95 (s broad, ÍH), 6.15 (s, ÍH), 7.0-7.2 (, 3H), 7.4 (s, ÍH).

EXAMPLE 1.2 Synthesis of N- (4-ethoxyphenyl) -8- (2-ethyl-6-methylbenzylamino) -2, 3-dimethylimidazo [1, 2- a) pyridin-6-carboxamide 2,3-Dimethyl-8- (2-ethyl-6-methylbenzylamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.15 g, 0.44 mmol) and o-benzotriazole-1- tetrafluoroborate IL-N, N, N ', N'-tetramethyluronium (TBTU) (0.14 g, 0.44 mmol) were added to 10 ml of methylene chloride, 4-ethoxyaniline (0.19 g, 1.4 mmol) and the reaction mixture were added. it was stirred at room temperature for 72 hours. The solvent was evaporated under reduced pressure and the residue was added to a column with silica gel and purified by chromatography using methylene chloride-methanol (95: 5) as eluent. The residue was treated with a hot mixture of hexane: ethyl acetate (2: 1) and the product was filtered and dried to obtain 0.14 g (74%) of the desired compound as white crystals.

H-NMR (300 MHz, CDC13): d 1.2 (t, 3H), 1.4 (t, 3H), 2.35 (s, 9H), 2.65 (q, 2H), 4.0 (q, 2H), 4.35 (d, 2H) ), 4.9 (t, ÍH), 6.55 (s, ÍH), 6.85 (d, 2H), 7.0-7.2 (, 3H), 7.5 (d, 2H), 7.9 (s, ÍH), 8.15 (s, ÍH) ).

EXAMPLE 1.3 Synthesis of N- [2- (dimethylamino) -2-oxoethyl] -8- (2-ethyl-6-methylbenzylamino) -N, 2, 3-trimethylimidazo [1,2-a) pyridine-6-carboxamide 2,3-Dimethyl-8- (2-ethyl-6-methylbenzylamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.13 g, 0.38 mmol) and o-benzotriazole-1- tetrafluoroborate IL-N, N, N ', N' -tetramethyluronium (TBTU) (0.12 g, 0.38 mmol) were added to 10 ml of methylene chloride. N, N-Dimethyl-2-methylaminoacetamide (0.088 g, 0.38 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography using methylene chloride methanol as eluent (95: 5) which gave 80 mg (48%) of the title product.

NMR 1E (500 MHz, CDC13): d 1.2 (t, 3H), 2.3 (s, 6H), 2.35 (s, 3H), 2.65 (q, 2H), 2.75 (s, 6H), 2.95 (s, 3H) ), 3.15 (s, 2H), 4.35 (broad s, 2H), 4.85 (s broad, ÍH), 6.25 (s, ÍH), 7.0-7.2 (m, 3H), 7.45 (s, ÍH).

EXAMPLE 1.4 Synthesis of (8- (2-ethyl-6-methylbenzylamino) -2, 3-dimethylimidazo [1, 2-a] pi idin -il) (4-me ti Ipiper azi no) methanone 2,3-Dimethyl-8- (2-ethyl-6-methylbenzylamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.5 g, 1.48 mmol) and o-benzotriazole-1- tetrafluoroborate IL-N, N, N ', N' -tetramethyluronium (TBTU) (0.48 g, 0.15 mmol) were added to 20 ml of methylene chloride and the mixture was stirred for 5 minutes. N-Ethylpiperazine (0.16 g, 1.6 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and purification of the residue by column chromatography on silica gel using methylene chloride-methanol (9: 1) as eluent, gave 0.46 g (74%) of the title compound.

NMR IE (500 MHz, CDC13): d 1.22 (t, 3H), 2.34 (s, 3H), 2.36 (s, 3H), 2.38 (s, 3H), 2.47 (s broad, 4H), 2.71 (q, 2H), 2.80 (s, 3H), 3.65 (s broad, 4H), 4.36 (d, 2H), 4.94 (t, ÍH), 6.19 (s, ÍH), 7.04-7.18 (m, 3H), 7.42 ( Yes H) .

EXAMPLE 1.5 Synthesis of 1- ((8- (2-ethyl-6-methylbenzylamino) -2,3-dimethylimidazo [1 f2-a] pyridin-6-yl) carbonyl) -2- (s) -pyrrolidinecarboxamide 2,3-Dimethyl-8- (2-ethyl-6-methylbeneilamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.15 g, 0.44 mmol) and o-benzotriazole-1 tetrafluoroborate IL-N, N, N ', N -tetramethyluronium (TBTU) (0.14 g, 0.45 mmol) and triethylamine (0.05 g, 0.5 mmol) were added to 10 ml of methylene chloride and the mixture was stirred for 10 minutes. (S) -prolinamide (0.016 g, 0.45 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure and purification of the residue by column chromatography on silica gel using methylene chloride-methanol (9: 1) as eluent and crystallization from diethyl ether gave 0.07 g (36%) of the Title.

X H NMR (500 MHz, CDC13): d 1.21 (t, 3H), 2.1-2.2 (m, 4H), 2.33 (s, 3H), 2.35 (s, 3H), 2.37 (s, 3H), 2.70 (q , 2H), 3.65-3.75 (, 2H), 4.36 (d, 2H), 4.80 (s broad, ÍH), 4.94 (s, ÍH), 5.88 (s, ÍH), 6.33 (s, ÍH), 6.98 (s, ÍH), 7.04-7.19 (m, 3H), 7.54 (s, ÍH).

EXAMPLE 1 . 6 Synthesis of 1 to 8- (2-ethyl-6-methyl-benzyl amino) -N-hydroxy-2, 3-dimethylimidazo [1, 2-a] pyridine-6-carboxamide 2,3-Dimethyl-8- (2-ethyl-6-ethylbeneilamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.15 g, 0.45 mmol) and o-benzotriazole-1- tetrafluoroborate il-N, N, N ', N' -tetramethyluronium (TBTU) (0.14 g, 0.45 mmol), triethylamine (0.1 g, 0.99 mmol) and hydroxylamine hydrochloride (0.031 g, 0.46 mmol) in 5 ml of dimethylformamide a. The title compound was prepared according to Example 1.5 (Yield: 0.016 g, 10%). 1K NMR (500 MHz, CDC13): d 1.15 (broad s, 3H), 2.25 (broad s, 9H), 2.6 (broad s, 2H), 4.25 (broad s, 2H), 4.95 (s broad, ÍH), 6.45 (broad s, ÍH), 6.9-7.1 (, 3H), 7.75 (s broad, ÍH).

EXAMPLE 1.7 Synthesis of (2-ethyl-6-methylbenzylamino) -N- (2- (2-hydroxyethoxy) ethyl) -2, 3 -dimet i limi dazo [1,2-a] pyridine-6-carboxamide 2,3-Dimethyl-8- (2-ethyl-6-methylbenzylamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.3 g, 0.88 mmol) and o-benzotriazole-1 tetrafluoroborate il-N, N, N ', N' -tetramethyluronium (TBTU) (0.29 g, 0.90 mmol) and 2- (2-aminoethoxy) ethanol (0.2 g, 1.9 mmol) in 10 ml of methylene chloride. The title compound was prepared according to Example 1.5 (Yield: 0.24 g, 80%).

H-NMR (500 MHz, CDC13): d 1.25 (t, 3H), 2.25 (s, 3H), 2.3 (s, 3H), 2.35 (s, 3H), 2.75 (q, 2H), 3.4-3.45 (m, 2H), 3.55-3.7 (m, 6H), 4.35 (d, 2H), 5.05 (t, ÍH), 6.45 (s, ÍH), 7.0-7.2 (, 4H), 7.5 (s, ÍH).

EXAMPLE 1.8 Synthesis of (8- (2-ethyl-6-methylbenzylamino) -2, 3-dimethyl imidazo [1 r2-a] pyridin-6-yl) (3-hydroxy-l-pi rrol i di nil) methanone 2,3-Dimethyl-8- (2-ethyl-6-methylbenzylamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.15 g, 0.44 mmol) and o-benzotriazole-1- tetrafluoroborate il-N, N, N ', N' -tetramethyluronium (TBTU) (0.14 g, 0.44 mmol) and 3-pyrrolidinol (0.12 g, 1.4 mmol) in 10 ml of methylene chloride. The title compound was prepared according to Example 1.4. Crystallization was from ethyl acetate: hexane (2: 1) (Yield: 0.24 g, 80%).

AH NMR (300 MHz, CDC13): d 1.23 (t, 3H), 1.93 (broad s, 2H), 2.33 (s, 3H), 2.34 (s, 3H), 2.41 (s, 3H), 2.70 (q, 2H), 3.51-3.89 (m, 4H), 4.35 (d, 2H), 4. 38-4.55 (m, ÍH), 5.04 (s broad, ÍH), 6.35 (s, ÍH), 7.01-7.16 (, 3H), 7.51 (s, ÍH).

EXAMPLE 1.9 Synthesis of N- (3, 4-hydroxy phenethyl) -8- (2-ethyl-6-methylbenzylamino) -2, 3-dimethyl imidazo [1,2-a] pyridine-6-carboxamide 2,3-Dimethyl-8- (2-ethyl-6-methylbeneilamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.15 g, 0.44 mmol) and o-benzotriazole-1 tetrafluoroborate IL-N, N, N ', N' -tetramethyluronium (TBTU) (0.14 g, 0.45 mmol) were added to 10 ml of dimethylformamide and the mixture was stirred for 5 minutes. 3,4-Dihydroxyphenethylamine (0.27 g, 1.4 mmol) and triethylamine (0.28 g, 1.4 mmol) were added, and the reaction mixture was stirred at room temperature for 72 hours. The solvent was evaporated under reduced pressure and purification of the residue by column chromatography on silica gel using methylene chloride methanol (9: 1) as eluent and crystallization from acetonitrile gave 0.059 g (28%) of the title compound .

X H NMR (400 MHz, DMSO-d 6): d 1.15 (t, ÍH), 2.22 (s, 3H), 2.33 (s, 3H), 2.37 (s, 3H), 2.65-2.74 (m, 4H), 3.41 (q, 2H), 4.37 (d, 2H), 4.85 (t, ÍH), 6.48 (dd, ÍH), 6.63-6.66 (m, 2H), 6.70 (d, ÍH), 7.07-7.21 (m, 3H ), 8.04 (d, ÍH), 8.49 (t, ÍH), 8.63 (s, ÍH), 8.75 (s, ÍH).

EXAMPLE 1.10 Synthesis of 8- (2-ethyl-6-methylbenzylamino-3- (hydroxymethyl) -2-methyl-6- (morpholinocarbonyl) -imidazo [1, 2- a] pir idina 8- (2-Ethyl-6-methylbenzylamino) -3-hydroxymethyl-2-methylimidazo [1,2-a] pyridine-6-carboxylic acid (0.012 g, 0.034 mmol) and o-benzotriazole-1- tetrafluoroborate il-N, N, N ', N' -tetramethyluronium (TBTU) (0.011 g, 0.034 mmol) and morpholine (0.009 g, 0.1 mmol) in 1 ml of methylene chloride. The title compound was prepared according to Example 1.1. (Yield: 0.008 g, 56%). 1U-NMR (300 MHz, DMSO-d6): d 1.23 (t, 3H), 2.33 (s, 3H), 2.39 (s, 3H), 2.72 (q, 2H), 3.74 (broad s, 8H), 4.37 ( d, 2H), 4.85 (s, 2H), 5.02 (t, ÍH), 6.27 (d, ÍH), 7.06-7.22 (m, 3H), 7.75 (d, ÍH).

EXAMPLE 1.86 Synthesis of N- ((8- (2-ethyl-6-methylbenzyl) amino) -2, 3-dimet i 1 imidazo [1,2- a] pyridin-6-yl) carbonyl) -guanidine 2,3-Dimethyl-8- (2-ethyl-6-methylbenzylamino) -imidazo [1,2-a] pyridine-6-carboxylic acid (0.5 g, 1.5 mmol), diisopropylethylamine (0.57 g, 1.5 mmol) and Guanidine carbonate (0.53 g, 2.9 mmol) were added to 10 ml of dimethylformamide. O-Benzotriazol-1-yl-N, N, N ', N' -tetramethyluronium (TBTU) tetrafluoroborate (0.48 g, 1.5 mmol) was added and the reaction mixture was stirred at 50 ° C for 3 hours. The solvent was evaporated under reduced pressure and purification of the residue by column chromatography on silica gel using methylene chloride-methanol (100: 15) as eluent and crystallization from diethyl ether gave 0.12 g (21%) of the Title.

NMR 1E (500 MHz, CDC13): d 1.1 (t, 3H), 2.25 (s, 3H), 2.3 (s, 3H), 2.35 (s, 3H), 2.7 (q, 2H), 4.35 (d, 2H) ), 4.8 (s broad, ÍH), 6.9 (s, ÍH), 7.05-7.2 (, 3H), 8.25 (s, ÍH).

EXAMPLE 1.87 Synthesis of 4- (2- (((8- (2-ethyl-6-methylbenzylamino) -2, 3-dimethylimidazo [1,2- a] pyridin-6-yl) carbonyl) amino) ethoxy) -4- oxob? tanoico 2, 3-Dimethyl-8- (2-ethyl-6-methylbenzylamino) -N-hydroxyethyl-imidazo [1,2-a] pyridine-6-carboxamide (250 mg, 0.263 mmol) and succinic anhydride (100 mg, 1.00 mmol) were added to 7 ml of acetone. The mixture was refluxed for 48 hours. The precipitated product was filtered and washed with acetone and ether for 288 mg (91%) of the title compound. 1 E NMR (500 MHz, DMSO): d 1.16 (t, 3H), 2.24 (s, 3H), 2.35 (s, 3H), 2.39 (s, 3H), 2.48-2.58 (m, 4H), 2. 70 (q, 2H), 3.54 (q, 2H), 4.19 (t, 2H), 4.39 (d, 2H), 4.90 (t, ÍH), 6.72 (s, ÍH), 7.09-7.22 (m, 3H), 8.08 (s, ÍH), 8.59 (t, ÍH), 12.25 (s, ÍH). Examples 11-85 were prepared by parallel synthesis using the following method: E REACTION SYSTEM 1 Solution A: 0.149 mmol in 1 ml of dimethylformamide Solution B (TBTU): 0.297 mmol in 1 ml of dimethylformamide Solution C + D: amine (C) (0.297 mmol in 1 ml of dimethylformamide) + TEA (D) (0.594 mmol in 1 ml of dimethylamine) To a solution A ( 300 μl) were added solution B (150 μl) and solution C + D (150 μl). The reaction was stirred at room temperature overnight. The solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane / methanol (9/1) (600 μl) and filtered through a pad of silica gel (100 mg) and the gel was washed with dichloromethane / methanol (9/1) (0.5-). 1.0 ml). The filtrate was evaporated under reduced pressure to give the desired compounds. (If necessary, the compounds were purified by preparative HPLC (High Resolution Liquid Chromatography). The analyzes of the examples were performed by HPLC and the compounds were identified by LC mass spectroscopy. All the compounds prepared in Examples 11-85 showed a mass spectrum that confirmed the proposed structure. As the initial compound A in the reactions the following compounds were used.

"A4 A5 As the initial compound C in the reaction raised the following amines.

HN x, O '^^^ H, ^ N ^ NH, fY. C13 C1 C15 C16 C17 C18 Examples 11-85 were prepared according to Reaction Scheme 1. The nitrogen of the primary or secondary amino is the nitrogen involved in the reaction. for example Al + C5- > Example 27 To C5 Example 27 An + Cn - Example 11-85 2. PREPARATION OF INTERMEDIARIES EXAMPLE 2. 1 Synthesis of 8- (2-ethylbenzyl amino) -2, 3-dimethyimido zo [1 r 2-a] pyrim din-6-carboxylic acid The 8- (2-ethylbenzylamino) -2,3-di-ethylimidazo [1,2- a] pyridine-6-carboxamide (1.0 g, 0.0031 mol) and sodium hydroxide (1.2 g, 0.031 mol) were dissolved in ethanol ( 95%) (30 ml) and heated to reflux overnight. The solvent was evaporated under reduced pressure and water was added to the residue. The pH was adjusted to 7 by the addition of 2.6 ml of concentrated hydrochloric acid and the solid which precipitated was isolated by filtration, washed with water and dried to give 1.0 g (99%) of the title compound. NMR tE (300 MHz, DMSO-d6): d 1.2 (t, 3H), 2.25 (s, 3H), 2.35 (s, 3H), 2.7 (q, 2H), 4.45 (d, 2H), 6.3 (s) , ÍH), 6.45 (t, ÍH), 7.05-7.25 (m, 4H), 7.95 (s, ÍH).

EXAMPLE 2.2 Synthesis of 8- (2,6-diethylbenzylamino) -2,3-dimethyl imidazo [1, 2-a] pyridin-6-carboxylic acid 8- (2,6-Diethylbene-amino) -2,3-dimethylimidazo [1,2-a] pyridine-6-carboxamide (1.5 g, 0.0043 mol) and sodium hydroxide (1.7 g, 0.043 mol) were dissolved in ethanol (at 95%) (30 ml). The title compound was prepared according to Example 1.4. (Yield: 1.5 g, 99%).

NMR XH (400 MHz, DMSO-d6): d 1.14 (t, 6H), 2.22 (s, 3H), 2.37 (s, 3H), 2.67 (q, 4H), 4.37 (d, 2H), 4.89 (t, ÍH), 6.68 (s, ÍH), 7.11 (d, 2H), 7.23 (t, ÍH), 8.09 (s, ÍH).

EXAMPLE 2.3 Synthesis of 8- (2,6-dimethyl-4-fluorobenzyl amino) -2,3-dimethyl imidazo [1,2-a] pyridin-6-carboxylic acid The mesylate of 8- (2,6-dimethyl-4-fluorobenzylamino) -2,3-dimethyl imidazo [1,2-a] pyridine-6-carboxamide (1.47 g, 0.0034 mol) and sodium hydroxide (1.7 g) , 0.034 mol) were dissolved in ethanol (95%) (30 ml). The title compound was prepared according to Example 2.1. (Yield: 1.1 g, 95%). 1 E NMR (400 MHz, DMSO-d6): d 2.23 (s, 3H), 2.34 (s, 6H), 2.36 (s, 3H), 4.31 (d, 2H), 5.04 (s broad, ÍH), 6.70 ( s, ÍH), 6.90 (d, 2H), 8.02 (s, ÍH).

EXAMPLE 2. 4 Synthesis of the acid 8- (2-I-sopropyl-6-methylbenzyl amino) -2, 3 -dimethyl imi dazo [l r 2-a] pyri din -6-carboxy li The mesylate of 8- (2-isopropyl-6-methylbeneilamino) -2, 3-dimethylimidazo [1,2- a] pyridine-6-carboxamide (1.2 g, 0.0027 mol) and sodium hydroxide (1.1 g, 0.027 mol ) were dissolved in ethanol (95%) (25 ml). The title compound was prepared according to Example 2.1. (Yield: 1.1 g, 95%).

NMR I (300 MHz, DMSO-d6): d 1.69 (d, 6H), 2.74 (s, 3H), 2.85 (s, 3H), 2.89 (s, 3H), 3.73 (, ÍH), 4.90 (d, 2H), 5.48 (t, ÍH), 7.19 (s, ÍH), 7.55-7.61 (, ÍH), 7.70-7.76 (m, 2H), 8.60 (s, ÍH).

EXAMPLE 2. 5 Synthesis of the acid 8- (2-ethyl-l-6-methylbenzyl amino) -2, 3-dimet y 1 imi da zo [1, 2-a] pyri din-6-carboxylic acid The mesylate of 8- (2-ethyl-6-methylbenzylamino) -2,3-dimethylimidazo [1,2- a] pyridine-6-carboxamide (11.0 g, 0.025 mol) and sodium hydroxide (7.0 g, 0.17 mol) they were dissolved in 120 ml of ethanol (95%) and heated to reflux for 20 hours. The solvent was evaporated under reduced pressure and 150 ml of water was added to the residue. The pH was adjusted to 5 by the addition of concentrated hydrochloric acid and acetic acid, and the solid which precipitated was isolated by filtration, washed with water and acetone, and dried to give 7.6 g (88%) of the title compound.

NMR 1E (500 MHz, DMSO-d6): d 1.15 (t, 3H), 2.26 (s, 3H), 2.34 (s, 3H), 2.39 (s, 3H), 2.69 (q, 2H), 4.38 (d, 2H), 5.2 (s broad, ÍH), 6.73 (s, ÍH), 7.07-7.2 (, 3H), 8.12 (s, ÍH).

EXAMPLE 2. 6 Synthesis of 8- (2-ethyl-6-methylbenzyl amino) -3-hydroxymethyl-2-methylimidazo [1, 2-a] pi and din-6-carboxylic acid 8- (2-Ethyl-6-methylbenzylamino) -3-hydroxymethi 1-2-methylimidazo [1,2-a] pyridine-6-carboxamide (0.02 g, 0.057 mmol) and sodium hydroxide (0.02 g, 0.29 mmol ) were dissolved in 1 ml of ethanol (95%) and heated to reflux for 20 hours. The solvent was evaporated under reduced pressure and 1 ml of water was added to the residue. The pH was adjusted to 5 by the addition of acetic acid and the solid was precipitated, isolated by filtration, washed with water and dried to give 0.012 g (60%) of the title compound.

NMR aH (300 MHz, DMSO-d6): d 1.14 (t, 3H), 2.22 (s, 3H), 2.33 (s, 3H), 2.67 (q, 2H), 4.33 (d, 2H), 4.55 (s) broad, IH), 4.67 (s, 2H), 6.83 (s, ÍH), 7.06-7.24 (m, 3H), 8.15 (s, ÍH).

BIOLOGICAL TESTS I. Experiments in vi tro Inhibition of acid secretion in isolated rabbit gastric glands The inhibitory effect on the secretion of in vi tro acid in isolated gastric glands of rabbit was measured as described by Berglindh et al. (1976) Acta Physiol. Scand. 97, 401-414.

Determination of the activity of H +, K + -ATPase Membrane vesicles (2.5 to 5 μg) were incubated for 15 minutes at + 37 ° C in 18 mM Pipes buffer / Tris pH 7.4 containing 2 mM magnesium chloride, 10 mM potassium chloride and 2 mM ATP. ATPase activity was estimated as the release of inorganic phosphate from ATP, as described by LeBel et al. (1978) Anal. Biochem. 85, 86-89. 2. Experiments in vivo.

Inhibitory effect on the secretion of acid in female rats Female rats of the Sprague-Dawley strain are used. These were equipped with cannulated fistulas in the stomach (lumen) and the upper part of the duodenum, for the collection of gastric secretions and the administration of test substances, respectively. A recovery period was left 14 days after surgery, before the test began. Before the secretory tests, the animals were deprived of food but not of water for 20 hours. The stomach is repeatedly washed through the gastric cannula with tap water (+ 37 ° C), and 6 ml of Ringer-glucose were administered subcutaneously. Acid secretion is stimulated with 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 gastric secretions are collected in fractions of 30 minutes. The test substances or the vehicle are administered either 60 minutes after the start of the stimulation (intravenous and intraduodenal dosing, 1 ml / kg), or 2 hours before the start of 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. Gastric juice sample is titrated at pH 7.0 with 0.1 M sodium hydroxide, and the acid output is calculated as the product of the volume of the titrant and the concentration. The additional calculations are based on the average group responses of 4 to 6 rats. In the case of administration during stimulation; the acid exit during the periods after the administration of the test substance or the vehicle are expressed as fractional responses, adjusting the acid output in the period of 30 minutes preceding the administration, to 1.0. The percent inhibition is calculated from the fractional responses promoted by the test compound and the vehicle. In the case of administration prior to stimulation, the percentage inhibition is calculated directly from the acid output or performance recorded after the test compound and the vehicle.

Bi odi esponibilidad in rat Adult rats of the Sprague-Dawley strain are used. One to three days' before the experiments all the rats are prepared by cannulation of the left carotid artery under anesthesia. The rats used for the intravenous experiments are also cannulated in the jugular vein (Popovic (1960) J. App. Physiol. 15.277-728). The cannulas are exteriorized in the neck. Blood samples (0.1-0.4 g) are drawn repeatedly from the carotid artery at intervals up to 5.5 hours after the dose is administered. The samples are frozen until the analysis of the test compound. Bioavailability is evaluated by calculating the quotient between the area under the blood / plasma concentration (AUC) curve after (i) intraduodenal (id) or oral (po) administration and (ii) intravenous (iv) administration from the rat or the dog, respectively. The area under the blood concentration curve vs. time, AUC, is determined by the trapezoidal / logarithmic linear rule and extrapolated to infinity by dividing the last blood concentration determined by the constant of the rate of elimination in the terminal phase. The systemic bioavailability (F%) after intraduodenal or oral administration is calculated as F (%) = (AUC (p.? Or i.d.) / AUC (i.v.)) x 100.

Inhibition of gastric acid secretion and bioavailability in consci ent dogs.

Labrador retrievers are used Harrier of any sex. These are equipped with a duodenal fistula for the administration of test compounds or vehicle, and a cannulated gastric fistula or a bag of Heidenhaim for the collection of gastric secretion. Before the secretion tests, the animals are fasted for approximately 18 hours but they are given water freely. The secretion of gastric acid is stimulated by up to 6.5 hours of infusion of histamine dihydrochloride (12 ml / h) at a dose that produces approximately 80% of the individual maximum secretory response, and gastric juice collected in consecutive fractions of 30 minutes. The test substance or vehicle is administered orally, i.d. or i.v., 1 or 1.5 hours after the initiation of 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 is administered to the main stomach secretor of dog acid with Heidenham bag. The acidity of the gastric juice samples is determined by titration up to pH 7.0, and the gastric acid output is calculated. The acid exit in the collection periods after the administration of the test substance or the vehicle are expressed as the fractional responses, adjusting the acid exit in the fraction that precedes the administration to 1.0. The percent inhibition is calculated from the fractional responses promoted by the test compound and the vehicle. Blood samples are collected for analysis of the concentration of the test compound in plasma, at intervals up to 4 hours after dosing. The plasma is separated and frozen within 30 minutes after collection and subsequently analyzed. The systemic bioavailability (F%) after oral administration or i.d., is calculated as described above in the rat model.

It is noted that in relation to this date, the best method known by the applicant to bring the said invention into practice is that which is clear from the present description of the invention.

Claims (21)

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

1. A compound of Formula I R1 is a) H, b) CH3, or c) CH2OH; R is a) CH3 / or b) CH2CH3; R3 is a) H b) alkyl of 1 to 6 carbon atoms c) alkyl of 1 to 6 carbon atoms hydroxylated, or d) halogen; R 4 is a) H, b) alkyl of 1 to 6 carbon atoms, c) alkyl of 1 to 6 carbon atoms hydroxylated, or d) halogen; R5 is a) H, or b) halogen; R6 and R7 are independently selected substituents, comprising carbon, hydrogen, nitrogen, oxygen, sulfur, selenium, phosphorus or halogen atoms, which give compounds of Formula I of a molecular weight < c600, with the proviso that at least one of R6 and R7 can not be hydrogen, alkyl of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms hydroxylated, or alkyl of 1 to 6 carbon atoms substituted with alkoxy from 1 to 6 carbon atoms, and X is (a) NH, or (b) 0.

2. A compound according to claim 1, characterized in that R1 is CH3 or CH20H; R2 is CH3 or CH2CH3; R3 is CH3 or CH2CH3; R4 is CH3 or CH2CH3; R5 is H, Br, Cl, or F; R6 and R7 are independently (with the proviso that at least one of R6 and R7 can not be hydrogen, alkyl of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms hydroxylated or alkyl of 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms): a) hydrogen, b) alkyl of 1 to 6 carbon atoms, c) alkyl of 1 to 6 carbon atoms hydroxylated, d) alkyl of 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms, e) alkenyl of 2 to 6 carbon atoms, f) alkynyl of 2 to 6 carbon atoms, g) alkyl of 1 to 6 carbon atoms halogenated, h) cycloalkyl of. 3 to 8 carbon atoms, i) alkyl of 1 to 6 carbon atoms substituted with cycloalkyl, j) aryl, in which the aryl group represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, nitro, amino, (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2-N-, or CN or NH2S02, k) alkyl of 1 to 6 carbon atoms substituted with aryl, in which the aryl group represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, nitro, amino- (alkyl of 1 to 6 carbon atoms) - NH-, (alkyl of 1 to 6 carbon atoms) 2-N-, CN or NH2S02, 1) R8- (alkyl of 1 to 6 carbon atoms) -, wherein R8 e s NH2C = 0-, (alkyl of 1 to 6 carbon atoms) -NHC = 0-, (alkyl of 1 to 6 carbon atoms) 2NC = 0-, (alkyl of 1 to 6 carbon atoms) -OOC- , NH2S02-, (alkyl of 1 to 6 carbon atoms) -S02-NH-, ArS02NH-, cyano, (alkyl of 1 to 6 carbon atoms) - CO-NH-, (alkyl of 1 to 6 carbon atoms) -OOCNH-, (C 1-6 alkyl) -0-, (C 7 -C 12 -alkyl- (C 1-6 alkyl) -SO-, (C 1-6 -alkyl) alkyl -S-, (alkyl of 1 to 6 carbon atoms) -S02-, (alkyl of 1 to 6 carbon atoms) -C = 0-, NH2-, (C 1-6 -alkyl) -NH-, (C 1-6 -alkyl) 2N-, ArCONH-, Ar (C 1-6 -alkyl) CONH, ArNHS02-, (Ar) 2 -N-S02-, (alkyl of 1 to 6 carbon atoms) -NHS02-, ArS-, ArSO-, ArS02-, ArC = 0-, NH2C0NH- (alkyl of 1 to 6 carbon atoms) -NHCONH-, (alkyl of 1 to 6 carbon atoms) 2-NCONH-, ArNHCONH-, (alkyl of 1 to 6 carbon atoms) 2-N-S02, Ar-0-, Ar-NH-, Ar (C 1-6 alkyl) N-, (C 1-6 -hydroxylated alkyl) -0 or morpholinyl; wherein Ar represents phenyl, pyridyl, thienyl, imidazolyl, indolyl, naphthyl or furanyl, optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH , CN, nitro, amino, (alkyl of 1 to 6 carbon atoms) -NH-, or (to the quil of 1 to 6 carbon atoms) 2N-, m). 7 to 12 carbon atoms, n) OH, O- (alkyl of 1 to 6 carbon atoms), or O- (alkyl of 1 to 6 hydroxy carbon atoms), H R9-N o) > V wherein RJ are R10-N independently hydrogen or alkyl of 1 to 6 carbon atoms, p) R11- (alkyl of 1 to 6 carbon atoms) -COO- (alkyl of 1 to 6 carbon atoms) -where R11 is HOOC-, (alkyl of 1 to 6 carbon atoms) -OOC- or an aminocarbonyl group with the formula wherein R12, R13 are the same or different, hydrogen, or alkyl of 1 to 6 carbon atoms. R6 and R7, together with the nitrogen atom to which they are attached, form a saturated or unsaturated ring optionally containing one or more additional heteroatoms (for example morpholine, piperazine, pyrrolidine, piperidine), optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, nitro, amino (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) ) 2-N-, CN, NH2S02, phenyl, NH2C0-, (C1-C6 alkyl) -CO-, the ring can be fused with an aromatic ring (such as tetrahydroquinoline), or a pharmaceutically acceptable salt of the same.

3. A compound according to claim 1 or 2, characterized in that R1 is CH3 or CH2OH; R2 is CH3, R3 is CH3 or CH2CH3; R4 is CH3 or CH2CH3; R5 is H, Br, Cl, or F; R6 and R7 are independently (with the proviso that at least one of R6 and R7 can not be H, alkyl of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms hydroxylated or alkyl of 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms): a) hydrogen b) alkyl of 1 to 6 carbon atoms, c) alkyl of 1 to 6 carbon atoms hydroxylated, d) alkyl of 1 to 6 carbon atoms substituted with alkoxy of 1 to 6 carbon atoms, e) alkyl of 1 to 6 carbon atoms halogenated, f) aryl, in which the aryl represents phenyl, pyridyl, imidazolyl, indolyl, or naphthyl, optionally substituted with one or more substituents selected of halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, (alkyl of 1 to 6 carbon atoms) -NH-, (alkyl of 1 to 6 carbon atoms) 2 -N-, or CN, g) alkyl of 1 to 6 carbon atoms substituted with aryl, in which the aryl group represents phenyl, pyridyl, imidazoli what, indolyl, 0 naphthyl, optionally substituted with one or more substituents selected from halogen, alkyl 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, or OH, h) R8- (alkyl of 1 to 6 carbon atoms) -, wherein R8 is NH2C = 0-, (alkyl of 1 to 6 carbon atoms) -NHC = 0-, (alkyl of 1 to 6 carbon atoms) 2NC = 0-, (alkyl of 1 to 6 carbon atoms) -OOC-, cyano, (alkyl of 1 to 6 atoms) carbon) -CO-NH-, (alkyl of 1 to 6 carbon atoms) -OOCNH-, (alkyl of 1 to 6 carbon atoms) -0-, (alkyl of 7 to 12 carbon atoms) -O- (alkyl of 1 to 6 carbon atoms) -SO-, (C 1-6 alkyl-S-, (C 1-6 alkyl) -C = 0-, ArCONH-, Ar (alkyl) 1 to 6 carbon atoms) CONH, ArC = 0-, NH2CONH- (alkyl of 1 to 6 carbon atoms) -NHCONH-, (alkyl of 1 to 6 carbon atoms) 2NCONH-, ArNHCONH-, (alkyl of 1 6-hydroxylated carbon atoms) -O- or morpholinyl, wherein Ar represents phenyl, pyridyl, imidazolyl, indolyl, 0 naphthyl optionally substituted with one or more substituents selected from halogen, alkyl 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, CN, i) alkyl of 7 to 12 carbon atoms, j) OH, k) R11- (alkyl of 1 to 6 carbon atoms ) -COO- (alkyl of 1 to 6 carbon atoms) -where R11 is HOOC-, or (alkyl of 1 to 6 carbon atoms) -OOC R6 and R7, together with the nitrogen atom to which they are attached , form a saturated or unsaturated ring optionally containing one or more heteroatoms (for example morpholine, piperazine, pyrrolidine, piperidine), optionally substituted with one or more substituents selected from halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, CF3, OH, nitro, amino, CN, NH2S02, phenyl, NH2CO-, (alkyl of 1 to 6 carbon atoms) -CO-, the ring can be fused with an aromatic ring (such as tetrahydroquinoline) .

4. The compound according to claims 1 to 3, characterized in that it is: • 2,3-dimethyl-8- (2-ethyl-6-methylbenzylamino) -6- (morpholinocarbonyl) -imidazo [1,2-a] pyridine, • N- (4-ethoxyphenyl) -8- (2-ethyl-6-methylbenzylamino) -2, 3-dimethylimidazo [1,2-a) pyridine-6-carboxamide, • N- [2- (dimethylamino) -2-oxoethyl] -8- (2-ethyl-6-methylbenzylamino) -N, 2, 3-trimeti limidazo [1,2-a) pyridine-6-carboxamide, • ( 8- (2-ethyl-6-methylbenzylamino) -2, 3-di-ethylimidazo [1,2- a] pyridin-yl) (4-methylpiperazino) methanone, • 1- ((8- (2-ethyl-6-) methylbenzylamino) -2,3-dimethylimidazo [1,2-a] pyridin-6-yl) carbonyl) -2- (s) -pyrrolidinecarboxamide, • 8- (2-ethyl-6-methylbenzylamino) -N-hydroxy-2 , 3-dimethylimidazo [1,2- a] pyridine-6-carboxamide, • (2-ethyl-6-methylbenzylamino) -N- (2- (2-hydroxyethoxy) ethyl) -2, 3-dimethyl imidazo [1, 2-a] pyridine-6-carboxamide, • (8- (2-ethyl-6-methylbenzylamino) -2, 3-di-ethylimidazo [1,2- a] pyridin-6-yl) (3-hydroxy-l- pyrrolidinyl) methanone, • N- (3,4-hydroxyphenethyl) -8- (2-ethyl-6-methylbeneilamino) -2,3-dimethylimidazo [1,2- a] pyridine-6-carboxamide, • 8- (2 -ethyl-6-methylbenzylamino-3- (hydroxymethyl) -2-methyl-6- (morpholinocarbonyl) -imidazo [1,2- a] pyridine, • N- ((8- (2-ethyl-6-methylbenzyl) amino) ) -2, 3-dimethylimidazo [1,2-a] pyridine -6-yl) carbonyl) -guanidine, • 4- (2- (((8- (2-ethyl-6-methylbenzylamino) -2,3-dimethylimidazo [1,2- a] pyridin-6-yl) carbonyl) -amino) ethoxy.) -4-oxobutanoic, or a pharmaceutically acceptable salt thereof.

5. A compound according to any of claims 1-4, characterized in that it is like a hydrochloride or mesylate salt.

6. The products containing a compound according to any of claims 1-5, and at least one antimicrobial agent as a combined preparation for simultaneous, separate or sequential use in the prevention or treatment of gastrointestinal inflammatory diseases.

7. The products of a compound according to any of claims 1-5, and at least one proton pump inhibitor as a combined preparation for simultaneous, separate or sequential use in the prevention or treatment of gastrointestinal inflammatory diseases.

8. A process for the preparation of a compound according to any of claims 1 to 5, wherein X is NH, characterized in the process because it comprises: a) the reaction of a compound of Formula II II with a compound of Formula III wherein R6 and R7 are as defined in claim 1, in an inert solvent, to a compound of Formula IV, IV b) the reaction of a compound of Formula IV wherein R6 and R7 are as defined in claim 1, with ammonia in a solvent inert to a compound of Formula V V c) the reduction of a compound of Formula V wherein R6 and R7 are as defined in claim 1, in an inert solvent under standard conditions to a compound of Formula VI VI d) the reaction of a compound of Formula VI wherein R6 and R7 are as defined in claim 1 with a compound of Formula VII VII wherein R2 is as defined in claim 1, Z is a leaving group and R9 represents hydrogen, CH3 or an ester group, in an inert solvent with or without a base to a compound of Formula VIII VIII e) the reaction of a compound of Formula VIII wherein R6, R7 and R2 are as defined in claim 1, and R9 is hydrogen, CH3 or an ester group with a compound of Formula IX IX wherein R3, R4 and R5 are as defined in claim 1, and Y is a leaving group in an inert solvent with or without a base, to a compound of Formula X X f) the reduction of a compound of the Formula X wherein R9 is an ester group in a solvent inert to a compound of Formula I, wherein R1 is CH2OH and X is NH.

9. A process for the preparation of a compound according to any of claims 1 to 5, characterized in that X is NH and R1 is hydrogen or CH3, characterized in that it comprises a) the reaction of a compound of Formula II II with an alcohol-like compound of the general formula R10-OH, wherein R10 is an alkyl group under standard conditions, to a compound of the Formula XI XI b) the reaction of a compound of Formula XI, wherein R10 is an alkyl group, with ammonia in an inert solvent under standard conditions to a compound of Formula XII XII c) the reduction of a compound of Formula XII, wherein R 10 is an alkyl group in an inert solvent under standard conditions to a compound of Formula XIII XIII d) the reaction of a compound of Formula XIII, wherein R10 is an alkyl group with a compound of Formula XIV wherein R2 is as defined in claim 1, Z is a leaving group and R11 represents hydrogen or CH3, in an inert solvent with or without a base to a compound of Formula XV XV e) the reaction of a compound of Formula XV wherein R 10 is an alkyl group, R 2 is as defined in claim 1 and R 11 is hydrogen or CH 3 with a compound of Formula IX IX wherein R3, R4 and R5 are as defined in claim 1 and Y is a leaving group in an inert solvent with or without a base to a compound of Formula XVI XVI f) the reaction of a compound of Formula XVI wherein R2, R3, R4 and R5 are as defined in claim 1, R10 is an alkyl group and R11 is hydrogen or CH3 with a compound of Formula III wherein R6 and R7 are as defined in claim 1, under standard conditions, up to a compound of Formula I wherein R1 is hydrogen or CH3 and X is NH.

10. A process for the preparation of a compound according to any of claims 1 to 5, characterized in that it comprises: a) the treatment a compound of the Formula XVII wherein R1, R2, R3, R4, R5 and X are as defined in claim 1 and R10 is an alkyl group, with acid or base under standard conditions, up to a compound of Formula XVIII XVIII b) the reaction of a compound of Formula XVIII wherein R1, R2, R3, R, R5 and X are as defined in claim 1, with a compound of Formula III wherein R6 and R7 are as defined in claim 1, in the presence of a coupling reagent in an inert solvent under standard conditions, up to a compound of Formula I.

11. A compound according to any of claims 1 to 5, for use in therapy.

12. A pharmaceutical formulation, characterized in that it contains a compound according to any of claims 1 to 5, as an active ingredient in combination with a pharmaceutically acceptable diluent or carrier.

13. The use of a compound according to any of claims 1 to 5, for the manufacture of a medicament for the inhibition of gastric acid secretion.

14. The use of a compound according to any of claims 1 to 5, for the manufacture of a medicament for the treatment of gastrointestinal inflammatory diseases.

15. The use of a compound according to any of claims 1 to 5, the manufacture of a medicament for the treatment or prophylaxis of conditions involving infection by Helicobacter pylori of the human gastric mucosa, wherein said salt is adapted to be administered in combination with at least one antimicrobial agent.

16. 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 5.

17. A pharmaceutical formulation for use in the treatment of gastrointestinal inflammatory diseases, wherein the active ingredient is a compound according to any of claims 1 to 5.

18. A pharmaceutical formulation for use in the treatment or prophylaxis of conditions involving infection by Helicobacter pylori, of the human gastric mucosa, wherein the active ingredient is a compound according to any of claims 1 to 5, in combination for the simultaneous, separate or sequential use or together with at least one antimicrobial agent.

19. A compound of Formula VIII characterized in that R2, R6 and R7 are as defined according to claim 1, and R9 is hydrogen, CH3 or an ester group.

20. A compound of the Formula X characterized in that R2, R3, R4, R5, R6 and R7 are as defined according to claim 1, and R9 is an ester group.

21. A compound of the formula XVIII characterized in that R1, R2, R3, R4, R5 and X are as defined in accordance with claim 1.