Amide derivatives

Abstract

A compound represented by the following general formula (I): 1

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is a divisional application of U.S. application Ser. No. 09/469,354 filed Dec. 22, 1999 which is a continuation-in-part of U.S. application Ser. No. 09/103,500, filed Jun. 24, 1998, the disclosures of which are expressly incorporated by reference herein in their entireties.

TECHNICAL FIELD

[0002] The present invention relates to novel amide derivatives having strong antibacterial activity against Helicobacter pylori.

BACKGROUND ART

[0003] Helicobacter pylori is a slightly aerobic gram-negative bacterium which was recently isolated from human gastric mucosa, and various published reports suggest its involvement in inflammation of alimentary tract, formation and recurrence of ulcer, and moreover, gastric cancer (Molecular Medicine, Vol. 31, pp.1304-1374, 1994).

[0004] For the treatment of gastrointestinal ulcers, medicaments such as H2 blockers or proton-pump inhibitors have been used so far. Since relation between Helicobacter pylori infection and gastric ulcer has been being clarified as explained above, an antibacterial agent such as amoxicillin has become practically used in combination, particularly from a viewpoint of prevention of recurrence. However, in most cases, ordinarily used antibacterial agents fail to achieve complete elimination of the bacteria. In addition, they may affect on intestinal bacterial flora due to their broad antibacterial spectra, and they often cause adverse effects such as diarrhea. Therefore, it has been desired to develop an antibacterial agent having potent antibacterial activity in alimentary tract that is specific against Helicobacter pylori.

[0005] The compound represented by the general formula (I) defined herein below wherein R7 is a benzyl group, and A and Y are an oxygen atom, and R4 and R5 are a hydrogen atom, and R6 is a propyl group, has been reported as intermediates of receptor models (Journal of American Chemical Society, Vol.115, pp.3548, 1993). However, it has not been known that this compound has an antibacterial activity against Helicobacter pylori.

DISCLOSURE OF THE INVENTION

[0006] The inventors of the present invention conducted researches to provide a novel anti-Helicobacter pylori agent, and as a result, they found that the compounds represented by the following general formula have excellent antibacterial activity against Helicobacter pylori, and can exhibit potent antibacterial activity in alimentary tract. The present invention was achieved on the bas of these findings.

[0007] The present invention thus provides amide derivatives represented by the following general formula (I) and salts thereof and solvates thereof and hydrates thereof: 2

[0008] wherein X represents R1(R2)(R3)C- where R1 represents a C3-C8 cycloalkyl group, an optionally substituted C6-C14 aryl group, an optionally substituted heterocyclic residue wherein the heterocyclic residue is one of furan ring, dihydrofuran ring, tetrahydrofuran ring, pyran ring, dihydropyran ring, tetrahydropyran ring, bexizofuran ring, dihydrobenzofuran ring, isobenzofuran ring, chromene ring, chroman ring, isochroman ring, thiophene ring, benzothiophene ring, pyrrole ring, pyrroline ring, pyrrolidine ring, imidazole ring, imidazoline ring, imidazolidine ring, pyrazole ring, pyrazoline ring, pyrazolidine ring, triazole ring, tetrazole ring, pyridine ring, pyridineoxide ring, piperidine ring, pyrazine ring, piperazine ring, pyrimidine ring, pyridazine ring, indolizine ring, indole ring, indoline ring, isoindole ring, isoindoline ring, indazole ring, benzinidazole ring, purine ring, quinolizine ring, quinoline ring, phthalazine ring, naphthylidine ring, quinoxaline ring, quinazoline ring, cinnoline ring, pteridine ring, oxazole ring, oxazolidine ring, isoxazole ring, isoxazolidine ring, thiazole ring, thiazylidine ring, isothiazole ring, isothiazolidine ring, dioxane ring, dithian ring, morpholine ring, and thiomorpholine ring, an optionally substituted C6-C14 aryloxy group, or an optionally substituted C7-C15 arylmethyl group; R2 and R3 independently represent hydrogen atom or a C1-C5 alkyl group, or R2 and R3 may combine to represent a C2-C7 alkylene group; or

[0009] X represents R7A- wherein R7 represents (i) a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group, an optionally substituted fluorenyl group or an optionally substituted heterocyclic group, (ii) an optionally substituted C6-C14 aryl group or (iii) an optionally substituted heterocyclic group, and A represents an oxygen atom or -N-R8 where R6 represents hydrogen atom or a C1-C5 alkyl group,

[0010] Y represents an oxygen atom or a sulfur atom,

[0011] R4 and R5 independently represent hydrogen atom or a C1-C5 alkyl group; and R6 represents hydrogen atom, a C1-C5 alkyl group which may optionally be substituted with a hydroxyl group, a hydroxyl group or a C1-C5 alkoxy group,

[0012] provided that the compounds wherein R7 is a benzyl group, A and Y are an oxygen atom, R4 and R5 are hydrogen atom, and R6 is a propyl group are excluded, or a salt thereof, or a solvate thereof or a hydrate thereof.

[0013] According to another aspect of the present invention, the present invention provides medicaments, preferably for the treatment of gastric diseases, e.g., gastritis, gastric ulcer, and gastric cancer, which comprise as an active ingredient a subs selected from the group consisting of the aforementioned amide derivatives and pharmaceutically acceptable salts thereof, and solvates thereof and hydrates thereof. The medicaments are preferably provided as pharmaceutical compositions comprising the aforementioned substance as an active ingredient together with one or more pharmaceutically acceptable additives. These medicaments can be used as anti-Helicobacter pylori agents for therapeutic and/or preventive treatment of digestive diseases related to Helicobacter pylori infection, for example, gastritis, gastric ulcer, gastric cancer, stomach malignant lymphoma, MALT lymphoma, duodenal ulcer, duodenal carcinoma and the like.

[0014] According to further aspects of the present invention, there are provided a method for treating digestive diseases related to Helicobacter pylori infection which comprises the step of administering to a mammal including a human a therapeutically effective amount of a substance selected from the group consisting of the aforementioned amide derivatives and pharmaceutically acceptable salts thereof, and solvates thereof and hydrates thereof, and a use of a substance selected from the group consisting of the aforementioned amide derivatives and pharmaceutically acceptable salts thereof, and solvates thereof and hydrates thereof for the manufacture of the above medicaments.

BEST MODE FOR CARRYING OUT THE INVENTION

[0015] In the general formula (I), examples of the C3-C8 cycloalkyl group represented by R1 include, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group, and cyclooctyl group. Examples of the C6-C14 aryl group include, for example, aromatic hydrocarbon groups consisting of one ring or two to approximately three condensed aromatic rings such as phenyl group, naphthyl group, and anthryl group.

[0016] As the residue of a heterocyclic compound, residues of heterocyclic compounds containing 1 to 4 heteroatoms selected from oxygen atom, sulfur atom, and nitrogen atom, and having 5 to 10 ring-membered atoms in total can be used. More specifically, examples of the residues of heterocyclic compounds include, for example, furan ring, dihydrofuran ring, tetrahydrofuran ring, pyran ring, dihydropyran ring, tetrahydropyran ring, benzofuran ring, dihydiobenzofuran ring, isobenzofuran ring, chromene ring, chroman ring, isochroman ring, thiophene ring, benzothiophene ring, pyrrole ring, pyrroline ring, pyrrolidine ring, imidazole ring, imidazoline ring, imidazolidine ring, pyrazole ring, pyrazoline ring, pyrazolidine ring, triazole ring, tetrazole ring, pyridine ring, pyridineoxide ring, piperidine ring, pyrazine ring, piperazine ring, pyrimidine ring, pyridazine ring, indolizine ring, indole ring, indoline ring, isoindole ring, isoindoline ring, indazole ring, benzimidazole ring, purine ring, quinolizine ring, quinoline ring, phthalazine ring, naphthylidine ring, quinoxaline ring, quinazoline ring, cinnoline ring, pteridine ring, oxazole ring, oxazolidine ring, isoxazole ring, isoxazolidine ring, thiazole ring, thiazylidine ring, isothiazole ring, isothiazoline ring, dioxane ring, dithian ring, morpholine ring, and thiomorpholine ring. Examples of the C5-C14 aryloxy group include, for example, phenyloxy group, naphthyloxy group, and anthryloxy group, and examples of the C7-C15 arylmethyl group include, for example, benzyl group, naphthylmethyl group, and anthrylmethyl group.

[0017] The C1-C5 alkyl group independently represented by R2 and R3 may be either a straight-or branched-chain alkyl, and examples include, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, and isopentyl group. Examples of the C2-C7 alkylene group represented by R2 combined with R3 include, for example, ethylene group, trimethylene group, tetramethylene group, pentamethylene group, bexamethylene group, and heptamethylene group, and these groups may have one or more branched chains.

[0018] As the C1-C5 alkyl group represented by R4 and R5, those explained for R2 and R3 can be independently used. In the present invention, R4 and R5 are preferably hydrogen atom.

[0019] As the C1-C5 alkyl group represented by R6, those explained for R2 and R3 can be used, and these alkyl groups may be substituted with at least one, preferably one hydroxy group. The C1-C5 alkoxy group represented by R6 may be a straight or branched chain group, and examples include, for example, methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, and isopentyloxy group. In the present invention, R6 is preferably an alkyl group, more preferably a methyl group.

[0020] As the C1-C10 alkyl group represented by R7 in the general formula (I) above, those having a straight or branched chain can be used, and examples include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, isopentyl group, hexyl group, isohexyl group, heptyl group, octyl group, nonyl group, and decyl group. These alkyl groups may optionally be substituted with a C6-C14 aryl group, a fluorenyl group or a heterocyclic group. The C6-C14 aryl group which can be a substituent on the alkyl group represented by R7 includes, for example, a C6-C14 aryl group such as phenyl group, naphtyl group or anthryl group. The heterocyclic group which can be a substituent on the alkyl group represented by R7 includes, for example, those described for R1.

[0021] As the C6-C14 aryl group and the heterocyclic group represented by R7, those described for the substituent on the C1-C10 alkyl group can be used.

[0022] R7 is preferably a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group, more preferably a C1-C5 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group, still more preferably a methyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group. In the present invention, R7 is particularly preferably a methyl group which is substituted with an optionally substituted C6-C14 aryl group or a methyl group which is substituted with an optionally substituted heterocyclic group.

[0023] A represents an oxygen atom or -N-R8 wherein R8 represents hydrogen atom or a C1-C5 alkyl group. The C1-C5 alkyl group represented by R8 includes methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, and isopentyl group. A is preferably an oxygen atom or -N-H.

[0024] Y represents an oxygen atom or a sulfur atom. Y is preferably an oxygen atom.

[0025] The aforementioned aryl group, residue of a heterocyclic compound, aryloxy group, and arylmethyl group may have one or more substituents at arbitrary positions on their rings. Examples of substituents include, for example, a halogen atom such as fluorine atom, chlorine atom, and bromine atom; a C1-C5 alkyl group such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, and tert-pentyl group; a C7-C15 aralkyl group such as benzyl group, phenylethyl group, and naphthylmethyl group; trifluoromethyl group; a C7-C15 alkoxy group such as methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, tert-butoxy group, pentyloxy group, and isopentyloxy group; a C7-C15 aralkyloxy group such as benzyloxy group, phenylethyloxy group, and naphthylmethyloxy group; a C1-C5 alkylenedioxy group such as methylenedioxy group, ethylenedioxy group, and propylenedioxy group; hydroxy group; nitro group; a C2-C6 alkylcarbonyloxy group such as acetoxy group, propionyloxy group, butyryloxy group, and valeryloxy group; carboxyl group; a C2-C6 alkoxycarbonyl group such as methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group, tertbutoxycarbonyl group, and pentyloxycarbonyl group; a C7-C16 aralkyloxycarbonyl group such as benzyloxycarbonyl group, phenylethyloxycarbonyl group, and naphthylmethyloxycarbonyl group; oxo group; a C2-C6 alkylcarbonyl group such as acetyl group, propioxyl group, butyryl group, and valeryl group; amino group; a C1-C5 monoalkylamino group such as methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, isobutylamino group, tert-butylamino group, pentylamino group, and isopentylamino group; a C2-C10 dialkylamino group such as dimethylamino group, ethylmethylamino group, diethylamino group, methylpropylamino group, and diisopropylamino group; a C2-C6 alkylcarbonylamimno group such as acetylamino group, propionylamino group, isopropionylamino group, butyrylamino group, and valerylamino group; a C2-C6 alkoxycarbonylamino group such as methoxycarbonylamino group, ethoxycarbonylamino group, propoxycarbonylamino group, isopropoxycarbonylamino group, butoxycarbonylamino group, isobutoxycarbonylamino group, tert-butoxycarbonylamino group, and pentyloxycarbonylamino group; a C7-C15 aralkyloxycarbonylamino group such as benzyloxycarbonylamino group, phenylethyloxycarbonylamino group, and naphthylmethyloxycarbonylamino group; carbamoyl group; a C2-C6 alkylcarbamoyl group such as methylcarbamoyl group, ethylcarbamoyl group, propylcarbamoyl group, butylcarbamoyl group, tert-butylcarbamoyl group, and pentylcarbamoyl group; a C6-C12 aryl group such as phenyl group, and naphthyl group and the like.

[0026] Among the compounds of the present invention represented by the above formula (I) wherein X is R1(R2)(R3)C-, preferred compounds include those wherein R1 is a C6-C14 aryl group which may optionally be substituted, a residue of a heterocyclic compound which may optionally be substituted, a C6-C14 aryloxy group which may optionally be substituted, or a C7-C15 arylmethyl group which may optionally be substituted, R2, R3, R4 and R5 are hydrogen atoms, R6 is a C1-C6 alkyl group, and Y is an oxygen atom. More preferred compounds include those wherein R1 is a C6-C14 aryl group which may optionally be substituted, a residue of a heterocyclic compound which may optionally be substituted, a C6-C14 aryloxy group which may optionally be substituted, or a C7-C15 arylmethyl group which may optionally be substituted, R2, R3, R4 and R5 are hydrogen atoms, R6 is methyl group, and Y is an oxygen atom.

[0027] Examples of particularly preferred compounds include:

[0028] N-(3-methylcarbamoylphenyl)-3-chlorophenylacetamide;

[0029] N-(3-methylcarbamoylphenyl)-4-chlorophenylacetamide,;

[0030] N-(3-methylcarbamoylphenyl)-3-bromophenylacetamide;

[0031] N-(3-methylcarbamoylphenyl)-4-bromophenylacetamide;

[0032] N-(3-methylcarbamoylphenyl)-3-methylphenylacetamide;

[0033] N-(3-methylcarbamoylphenyl)-4-methylphenylacetamide;

[0034] N-(3-methylcarbamoylphenyl)-3-methoxyphenylacetamide;

[0035] N-(3-methylcarbamoylphenyl)-4-methoxyphenylacetamide;

[0036] N-(3-methylcarbamoylphenyl)-3,4,5-trimethoxyphenylacetamide;

[0037] N-(3-methylcarbamoylphenyl)-3-benzyloxyphenylacetamide;

[0038] N-(3-methylcarbamoylphenyl)-1-naphthylacetamide;

[0039] N-(3-methylcarbamoylphenyl)-2-naphthylacetamide;

[0040] N-(3-methylcarbamoylphenyl)-3-indoly)acetamide;

[0041] N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide;

[0042] N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide;

[0043] N-(3-methylcarbamoylphenyl)-3,4-methylenedioxyphenylacetamide;

[0044] N-(3-methylcarbamoylphenyl)-2-chlorophenoxyacetamide;

[0045] N-(3-methylcarbamoylphenyl)-2,3-dichlorophenoxyacetamide;

[0046] N-(3-methylcarbamoylphenyl)-1-naphthyloxyacetide;

[0047] N-(3-methylcarbamoylphenyl)-2-naphthyloxyacetamide; and

[0048] N-(3-methylcarbamoylphenyl-3-(2-methoxyphenyl)propionamide.

[0049] Among the compounds of the above formula (I) wherein X is R7-A-, preferred compounds include those wherein R4 and R5 are hydrogen atom, A is an oxygen atom or -N-H and Y is an oxygen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof. More preferred compounds include those wherein R7 is a methyl group which is substituted with an optionally substituted C6-C4 aryl group or heterocyclic group, R4 and R5 are hydrogen atom, R6 is a methyl group, A is an oxygen atom or -N-H and Y is an oxygen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

[0050] Particularly preferred compounds include a compound selected from the group consisting of:

[0051] N′-methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide;

[0052] N′-methyl-3-(4-chlorobenzyloxycarbonylamino)benzamide;

[0053] N′-methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide;

[0054] N′methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide;

[0055] N′-methyl-3-(2-bromobenzyloxycarbonylamino)benzamide;

[0056] N′-methyl-3(2-methylbenzyloxycarbonylamino)benzamide;

[0057] N′-methyl-3-(3-methylbenzyloxycarbonylamino)benzamide;

[0058] N-methyl-3-(4-methylbenzyloxycarbonylamino)benzamide;

[0059] N′-methyl-3-(1-naphthylmethoxycarbonylamino)benzamide; and

[0060] N′-methyl-3-(2-naphthylmethoxycarbonylmino)benzamide;

[0061] or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

[0062] The amide derivatives of the present invention represented by the above general formula (I) can form a salt. Where one or more acidic groups exist examples of salts include, for example, metal sats such as lithium salt, sodium salt, potassium salt, magnesium salt, and calcium salt, and ammonium salts such as inorganic ammonium salt, methylammonium salt, dimethylammonium salt, trimethylammonium salt, and dicyclohexylammonium salt. Where one or more basic groups exist, examples of salts include, for example, mineral acid salts such as hydrochloride, hydrobromide, sulfate, nitrate, and phosphate, and organic acid salts such as methanesulfonate, benzenesulfonate, p-toluenesulfonate, acetate, propionate, tartrate, fumarate, maleate, malate, oxalate, succinate, citrate, benzoate, mandelate, cinnamate, and lactate. Pharmaceutically acceptable salts are preferred as the active ingredient of the medicaments of the present invention. The amide derivatives of the present invention represented by the above general formula (I) and salts thereof may also exist as solvates or hydrates. Any substances in the form of salts, solvates, or hydrates as well as compounds in free forms fall within the scope of the present invention.

[0063] As to the stereochemistry of asymmetric carbon atoms present in the amide derivatives of the present invention represented by the general formula (I), the atoms can independently be in (S), (R), or (RS) configuration. Isomers in pure forms based on one or more asymmetric carbon atoms, e.g., enantiomers and diastereoisomers, any mixtures of such isomers, racemates and the like fall within the scope of the present invention.

[0064] Examples of specific examples of the amide derivatives of the present invention represented by the above general formula (I) wherein X is R1(R2)(R3)C-, and Y is an oxygen atom, include those listed in Table 1. 1 TABLE 1 Compd. No. R1 R2 R3 R4 R5 R6 1 3 H H H H CH3 2 4 H H H H CH3 3 5 H H H H CH3 4 6 H H H H CH3 5 7 H H H H CH3 6 8 H H H H CH3 7 9 H H H H CH3 8 10 CH3 H H H CH3 9 11 CH3 CH3 H H CH3 10 12 CH3 CH3 CH3 H CH3 11 13 —(CH2)4— H H CH3 12 14 —(CH2)5— H H CH3 13 15 H H H H CH3 14 16 H H H H CH3 15 17 H H H H CH3 16 18 H H H H CH3 17 19 H H H H CH3 18 20 H H H H CH3 19 21 H H H H CH3 20 22 H H H H H 21 23 H H CH3 H CH3 22 24 H H H H CH3 23 25 H H H CH3 CH3 24 26 H H H H CH2CH3 25 27 H H H H CH2CH2CH3 26 28 H H H H (CH2)3CH3 27 29 H H H H (CH2)4CH3 28 30 H H H H CH2CH2OH 29 31 H H H H OH 30 32 H H H H OCH3 31 33 H H H H OCH2CH3 32 34 H H H CH2CH3 CH2CH3 33 35 H H H H CH3 34 36 H H H H CH3 35 37 H H H H CH3 36 38 H H H H CH3 37 39 H H H H CH3 38 40 H H H H CH3 39 41 H H H H CH3 40 42 H H H H CH3 41 43 H H H H CH3 42 44 H H H H CH3 43 45 H H H H CH3 44 46 H H H H CH3 45 47 H H H H CH3 46 48 H H H H CH3 47 49 H H H H CH3 48 50 H H H H CH3 49 51 H H H H CH3 50 52 H H H H CH3 51 53 H H H H CH3 52 54 H H H H CH3 53 55 H H H H CH3 54 56 H H H H CH3 55 57 H H H H CH3 56 58 H H H H CH3 57 59 H H H H CH3 58 60 H H H H CH3 59 61 H H H H CH3 60 62 H H H H CH3 61 63 H H H H CH3 62 64 H H H H CH3 63 65 H H H H CH3 64 66 H H H H CH3 65 67 H H H H CH3 66 68 H H H H CH3 67 69 H H H H CH3 68 70 H H H H CH3 69 71 H H H H CH3 70 72 H H H H CH3 71 73 H H H H H 72 74 H H H H CH3 73 75 H H H H CH3 74 76 H H H H CH3 75 77 H H H H CH3 76 78 H H H H CH3 77 79 H H H H CH3 78 80 H H H H CH3 79 81 H H H H CH3 80 82 H H H H CH3 81 83 H H H H CH3 82 84 H H H H CH3 83 85 H H H H CH3 84 86 H H H H CH3 85 87 H H H H CH3 86 88 H H H H CH3 87 89 H H H H CH3 88 90 H H H H CH3 89 91 H H H H CH3 90 92 H H H H CH3 91 93 H H H H CH3 92 94 H H H H CH3 93 95 H H H H CH3 94 96 H H H H CH3 95 97 H H H H CH3 96 98 H H H H CH3 97 99 H H H H CH3 98 100 H H H H CH3 99 101 H H H H CH3 100 102 H H H H CH3 101 103 H H H H CH3 102 104 H H H H CH3 103 105 H H H H CH3 104 106 H H H H CH3 105 107 H H H H CH3 106 108 H H H H CH3 107 109 H H H H CH3 108 110 H H H H CH3 109 111 H H H H CH3 110 112 H H H H CH3 111 113 H H H H CH3 112 114 H H H H CH3 113 115 H H H H CH3 114 116 H H H H CH3 115 117 H H H H CH3 116 118 H H H H CH3 117 119 H H H H CH3 118 120 H H H H CH3 119 121 H H H H CH3 120 122 H H H H CH3 121 123 H H H H CH3 122 124 H H H H CH3 123 125 H H H H CH3 124 126 H H H H CH3 125 127 H H H H CH3 126 128 H H H H CH3 127 129 H H H H CH3 128 130 H H H H CH3 129 131 H H H H CH3 130 132 H H H H CH3 131 133 H H H H CH3 132 134 H H H H CH3 133 135 H H H H CH3 134 136 H H H H CH3 135 137 H H H H CH3 136 138 H H H H CH3 137 139 H H H H CH3 138 140 H H H H CH3 139 141 H H H H CH3 140 142 H H H H CH3 141 143 H H H H CH3 142 144 H H H H CH3 143 145 H H H H CH3 144 146 H H H H CH3 145 147 H H H H CH3 146 148 H H H H CH3 147 149 H H H H CH3 148 150 H H H H CH3 149 151 H H H H CH3 150 152 H H H H CH3 151 153 H H H H CH3 152 154 H H H H CH3 153 155 H H H H CH3 154 156 H H H H CH3 155 157 H H H H CH3 156 158 CH3 H H H CH3 157 159 CH3 CH3 H H CH3 158 160 H H H H CH3 159 161 H H H H CH3 160 162 H H H H CH3 161 163 H H H H CH3 162 164 H H H H CH3 163 165 H H H H CH3 164 166 H H H H CH3 165 167 H H H H CH3 166 168 H H H H CH3 167 169 H H H H CH3 168 170 H H H H CH3 169 171 H H H H CH3 170 172 H H H H CH3 171 173 H H H H CH3 172 174 H H H H CH3 173 175 H H H H CH3 174 176 H H H H CH3 175 177 H H H H CH3 176 178 H H H H CH3 177 179 H H H H CH3 178 180 H H H H CH3 179 181 H H H H CH3 180 182 H H H H CH3 181 183 H H H H CH3 182 184 H H H H CH3 183 185 H H H H CH3 184 186 H H H H CH3 185 187 H H H H CH3 186 188 H H H H CH3 187 189 H H H H CH3 188 190 H H H H CH3 189 191 H H H H CH3 190 192 H H H H CH3 191 193 H H H H CH3 192 194 H H H H CH3 193 195 H H H H CH3 194 196 H H H H CH3 195 197 H H H H CH3 196 198 H H H H CH3 197 199 H H H H CH3 198 200 H H H H CH3 200 201 H H H H CH3 201 202 H H H H CH3 202 203 H H H H CH3 203 204 H H H H CH3 204 205 H H H H CH3 205 206 H H H H CH3 206 207 H H H H CH3 207 208 H H H H CH3 208 209 H H H H CH3 209 210 H H H H CH3 210 211 H H H H CH3 211 212 H H H H CH3 212 213 H H H H CH3 213 214 H H H H CH3 214 215 H H H H CH3 215 216 H H H H CH3 216 217 H H H H CH3 217 218 H H H H CH3 218 219 H H H H CH3 219 220 H H H H CH3 220 221 H H H H CH3 221 222 H H H H CH3 222 223 H H H H CH3 223 224 H H H H CH3 224 225 H H H H CH3 225 226 H H H H CH3 226 227 H H H H CH3 227 228 H H H H CH3 228 229 H H H H CH3 229 230 H H H H CH3 230 231 H H H H CH3 231 232 H H H H CH3 232 233 H H H H CH3 233 234 H H H H CH3 234 235 H H H H CH3 235 236 H H H H CH3 236 237 H H H H CH3 237 238 H H H H CH3 238 239 H H H H CH3 239 240 H H H H CH3 240 241 H H H H CH3 241 242 H H H H CH3 242 243 H H H H CH3 243 244 H H H H CH3 244 245 H H H H CH3 245 246 H H H H CH3 246 247 H H H H CH3 247 248 H H H H CH3 248 249 H H H H CH3 249 250 H H H H CH3 250 251 H H H H CH3 251 252 H H H H CH3 252 253 H H H H CH3

[0065] Examples of specific examples of the amide derivatives of the present invention represented by the above general formula (I) wherein X is R7A-, include those listed in Table 2. 2 TABLE 2 Compd. No. R7 A Y R4 R5 R6  1 CH3 O O H H CH3  2 NH O  3  4  5  6 254 O O NH NH O S O S H H CH3  7  8 255 O NH O O H H H  9  10 256 O NH O O H CH3 CH3  11  12 257 O NH O O H H CH2CH3  13  14 258 O NH O O H H CH2CH2CH3  15  16 259 O NH O O CH3 H CH3  17  18 260 O NH O O H H CH3  19  20 261 O NH O O H H CH3  21  22 262 O NH O O H H CH3  23  24 263 O NH O O H H CH3  25  26 264 O NH O O H H CH3  27  28 265 O NH O O H H CH3  29  30 266 O NH O O H H CH3  31  32 267 O NH O O H H CH3  33  34 268 O NH O O H H CH3  35  36 269 O NH O O H H CH3  37  38 270 O NH O O H H CH3  39  40 271 O NH O O H H CH3  41  42 272 O NH O O H H CH3  43  44 273 O NH O O H H CH3  45  46 274 O NH O O H H CH3  47  48 275 O NH O O H H CH3  49  50 276 O NH O O H H CH3  51  52 277 O NH O O H H CH3  53  54 278 O NH O O H H CH3  55  56 279 O NH O O H H CH3  57  58 280 O NH O O H H CH3  59  60 281 O NH O O H H CH3  61  62 282 O NH O O H H CH3  63  64 283 O NH O O H H CH3  65  66 284 O NH O O H H CH3  67  68 285 O NH O O H H CH3  69  70 286 O NH O O H H CH3  71  72 287 O NH O O H H CH3  73  74 288 O NH O O H H CH3  75  76 289 O NH O O H H CH3  77  78 290 O NH O O H H CH3  79  80 291 O NH O O H H CH3  81  82 292 O NH O O H H CH3  83  84 293 O NH O O H H CH3  85  86 294 O NH O O H H CH3  87  88 295 O NH O O H H CH3  89  90 296 O NH O O H H CH3  91  92 297 O NH O O H H CH3  93  94 298 O NH O O H H CH3  95  96 299 O NH O O H H CH3  97  98 300 O NH O O H H CH3  99 100 301 O NH O O H H CH3 101 102 302 O NH O O H H CH3 103 104 303 O NH O O H H CH3 105 106 304 O NH O O H H CH3 107 108 305 O NH O O H H CH3 109 110 306 O NH O O H H CH3 111 112 307 O NH O O H H CH3 113 114 308 O NH O O H H CH3 115 116 309 O NH O O H H CH3 117 118 310 O NH O O H H CH3 119 120 311 O NH O O H H CH3 121 122 312 O NH O O H H CH3 123 124 313 O NH O O H H CH3 125 126 314 O NH O O H H CH3 127 128 315 O NH O O H H CH3 129 130 316 O NH O O H H CH3 131 132 317 O NH O O H H CH3 133 134 318 O NH O O H H CH3 135 136 319 O NH O O H H CH3 137 138 320 O NH O O H H CH3 139 140 321 O NH O O H H CH3 141 CH3CH2 O O H H CH3 142 NH O 143 144 322 O NH O O H H CH3 145 146 323 O NH O O H H CH3 147 148 324 O NH O O H H CH3 149 150 325 O NH O O H H CH3 151 152 326 O NH O O H H CH3 153 154 327 O NH O O H H CH3 155 156 328 O NH O O H H CH3 157 158 329 O NH O O H H CH3 159 160 330 O NH O O H H CH3 161 162 331 O NH O O H H CH3 163 164 332 O NH O O H H CH3 165 166 333 O NH O O H H CH3 167 168 334 O NH O O H H CH3 169 170 335 O NH O O H H CH3 171 172 336 O NH O O H H CH3 173 174 337 O NH O O H H CH3 175 176 338 O NH O O H H CH3 177 178 339 O NH O O H H CH3 179 180 340 O NH O O H H CH3 181 182 183 184 185 186 341 O NH NCH3O NH NCH3 O O O S S S H H CH3 187 188 342 O NH O O H H H 189 190 343 O NH O O H CH3 CH3 191 192 344 O NH O O H H CH2CH3 193 194 345 O NH O O H H CH2CH2CH3 195 196 346 O NH O O CH3 H CH3 197 198 347 O NH O O H H CH3 199 200 348 O NH O O H H CH3 201 202 349 O NH O O H H CH3 203 204 350 O NH O O H H CH3 205 206 351 O NH O O H H CH3 207 208 352 O NH O O H H CH3 209 210 353 O NH O O H H CH3 211 212 354 O NH O O H H CH3 213 214 355 O NH O O H H CH3 215 216 356 O NH O O H H CH3 217 218 357 O NH O O H H CH3 219 220 358 O NH O O H H CH3 221 222 359 O NH O O H H CH3 223 224 360 O NH O O H H CH3 225 226 361 O NH O O H H CH3 227 228 362 O NH O O H H CH3 229 230 363 O NH O O H H CH3 231 232 364 O NH O O H H CH3 233 234 365 O NH O O H H CH3 235 236 366 O NH O O H H CH3 237 238 367 O NH O O H H CH3 239 240 368 O NH O O H H CH3

[0066] The amide derivatives of the present invention represented by the above general formula (I) wherein X is R1(R2)(R3)C-, and Y is an oxygen atom, can be prepared by, for example, the method explained below. 369

[0067] wherein R1, R2, R3, R4, R5 and R6 are the same as those defined above.

[0068] A carboxylic acid derivative represented by the above general formula (II) is allowed to react with a condensing agent such as dicyclohexylcarbodiimide, diphenylphospboryl azide, carbonyldiimidazole, oxalyl chloride, isobutyl chloroformate, and thionyl chloride, optionally in the presence of a base such as triethylamine and pyridine as required, to activate a carboxylic acid, and then the resulting intermediate is allowed to react with an aniline derivative represented by the above general formula (III), optionally in the presence of a base such as triethylamine and pyridine as required, to obtain a compound represented by the above general formula (I). As a solvent used in the condensation reaction, a suitable solvent may be appropriately chosen depending on a type of a condensing agent. Reaction conditions may also be appropriately chosen so as to be suitable for a condensing agent used.

[0069] In the above series of reactions, protection and deprotection of one or more functional groups may sometimes be required. In such a case, a protective group suitable for each of the reactive functional group may be chosen, and reaction procedures can be employed according to known methods described in the literature.

[0070] The amide derivatives of the present invention represented by the above general formula (I) wherein X is R7-A-, can be prepared by, for example, the method explained below. 370

[0071] wherein R7, R4, R5, and R6 are the same as those defined above.

[0072] An alcohol derivative represented by the above general formula (IV) is dissolved in an inert solvent such as acetonitrile, methylene chloride or chloroform, and allowed to be reacted with di(n-succinimidyl)carbonate in the presence of base such as triethylamine or pyridine to obtain an asymmetric carbonate compound (V) as an intermediate. The compound (V) is then dissolved in a polar solvent such as dimethylformamide, N-methylpyrrolidone or dimethylsulfoxide, and allowed to be reacted with the aniline derivative (VI) in the presence of base such as triethylamine or pyridine to obtain the compound (VII) i.e., the compound represented by the formula (I) wherein A and Y are an oxygen atom. 371

[0073] wherein R7, R4, R5, R6 and Y are the same as those defined above.

[0074] The isocyanate derivative (VIII) is dissolved in an inert solvent such as acetonitrile, methylene chloride or chloroform, and allowed to be reacted with the aniline derivative (VI) to obtain the compound (IX), i.e., the compound represented by the formula (I) wherein A is -NH.

[0075] In the above series of reactions, protection and deprotection of one or more functional groups may sometimes be required. In such a case, a protective group suitable for each of the reactive functional group may be chosen, and reaction procedures can be employed according to known methods described in the literature.

[0076] The compounds of the present invention represented by the above general formula (I) have excellent antibacterial activity against Helicobacter pylori, and they can exhibit potent antibacterial activity against Helicobacter pylori in stomach. Accordingly, the medicaments of the present invention are useful for therapeutic and/or preventive treatment of various digestive diseases related to the infection caused by Helicobacter pylori, for example, a disease selected from the group consisting of gastritis, gastric ulcer, gastric cancer; gastric malignant lymphoma, MALT lymphoma, duodenal ulcer, and duodenal carcinoma. More specifically, the compounds may preferably be used as medicaments for therapeutic treatment of gastritis, gastric ulcer and duodenal ulcer; medicaments for preventive treatment of gastric ulcer, duodenal ulcer, gastric malignant lymphoma, gastric cancer, and duodenal carcinoma; and medicaments for preventive treatment of recurrence of gastric ulcer and duodenal ulcer.

[0077] As an active ingredient of the medicament of the present invention, one or more substances selected from the group consisting of the compound represented by the above general formula (I) and a pharmaceutically acceptable salt thereof, and a solvate thereof and a hydrate thereof can be used. The medicament of the present invention may preferably be provided in the form of a pharmaceutical composition comprising the above substance as an active ingredient and one or more pharmaceutically acceptable additives for pharmaceutical preparations. In the pharmaceutical compositions, a ratio of the active ingredient to the pharmaceutical additive may be about 1% by weight to about 90% by weight.

[0078] The medicament of the present invention may be administered as a pharmaceutical composition for oral administration such as granules, subtilized granules, powders, hard capsules, soft capsules, syrups, emulsions, suspensions, and liquid drugs, or administered as a pharmaceutical composition for parenteral administration such as injections for intravenous, intramuscular or subcutaneous administration, drip infusions, and suppositories. A preparation prepared as a powdery pharmaceutical composition may be dissolved before use and used as an injection or a drip infusion.

[0079] Solid or liquid pharmaceutical additives may be used for preparation of the pharmaceutical compositions. The pharmaceutical additives may be either organic or inorganic materials. Examples of excipients used for manufacturing solid preparations include, for example, lactose, sucrose, starch, talc, cellulose, dextrin, china clay, and calcium carbonate. For the manufacture of liquid formulations for oral administration such as emulsions, syrups, suspensions, and liquids, for example, ordinary inert diluents such as water and vegetable oils may be used. In addition to the inert diluents, auxiliaries such as, for example, moistening agents, suspending aids, sweetening agents, aromatics, colorants, preservatives and the like may be formulated. Liquid preparations may be filled in capsules after their preparation that are made of an absorbable material such as gelatin. Examples of solvents or suspending mediums used for the manufacture of pharmaceutical preparations for parenteral administration such as injections and suppositories include, for example, water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, lecithin and the like. Examples of base materials used for preparation of suppositories include, for example, cacao butter, emulsified cacao butter, lauric lipid, Witepsol and the like. Methods for manufacturing the pharmaceutical preparations are not particularly limited, and any methods ordinarily used in the art may be employed.

[0080] A dose of the medicament of the present invention may generally be from about 0.01 to 5,000 mg per day for an adult based on the weight of the compounds of the present invention. However, it is preferred to suitably increase or decreased depending on age, conditions, symptoms or other of a patient. The daily dose may be administered once a day or two to three times a day with suitable intervals, or alternatively, intermittently administered with intervals of several days. When used as an injection, a dose of the medicaments of the present invention may be about 0.001 to 100 mg per day for an adult based on the weight of the compounds of the present invention.

EXAMPLES

[0081] The present invention will be explained more specifically by referring to the following examples. However, the scope of the present invention is not limited to these examples.

Example 1

Preparation of N-(3-methylcarbamoylphenyl)-3-chlorophenylacetamide (Compound No. 17 in Table 1)

[0082] 3-Chlorophenylacetic acid (192 mg) was dissolved in methylene chloride (8 ml), and oxalyl chloride (0.10 ml) and one drop of dimethylformamide were added to the solution. After stirring for 1 hour at room temperature, 3-aminobenzoylmethylamide (167 mg) and pyridine (0.19 ml) were added to the reaction mixture, and then stirred at room temperature overnight. After the solvent was evaporated under reduced pressure, water (10 ml) and 2N aqueous hydrochloric acid (l ml) were added to the residue, and the deposited crystals were collected by filtration and washed with water. These crystals were dried and added in ethyl acetate (6 ml), and then the mixture was heated under reflux for ten minutes. The mixture was cooled to room temperature, and the crystals were collected by filtration and washed with ethyl acetate to obtain the desired compound (233 mg, yield 68%).

[0083] Melting point: 165-166° C.

[0084] IR (KBr, cm−1): 3324, 1642, 1593, 1555.

[0085] NMR DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.68 (s, 2H), 7.25-7.42 (m, 5H), 7.48 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.02 (dd, J=1.8 Hz, 1.8 Hz, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.31 (s, 1H).

[0086] In similar manners to the method of Example 1, compounds of Examples 2-50 were prepared. Their physicochemical properties are set out below.

Example 2

Preparation of N-(3-methylcarbamoylphenyl)cyclohexylacetamide (Compound No. 4 in Table 1)

[0087] Melting point: 183° C.

[0088] IR (KBr, cm−1): 3293, 1657, 1640, 1588, 1535.

[0089] NMR (DMSO-d6, &dgr;): 0.99 m, 2H), 1.03-1.38 (m, 3H), 1.55-1.90 (m, 6H), 2.19 (d, J=7.0 Hz, 2 H), 2.76 (d, J=4.5 Hz, 3H), 7.34 (dd, J=7.8 Hz, 7.8 Hz, 1H, 7.45 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.34 (d, J=4.5 Hz, 1H), 9.95 (s, 1H).

Example 3

Preparation of N-(3-methylcarbamoylphenyl)phenylacetamide (Compound No. 7 in Table 1)

[0090] Melting point: 140-142° C.

[0091] NMR (DMSO-d6, &dgr;): 2.75 (d, J=4.5 Hz, 3H), 3.63 (s, 2H). 7.22-7.48 (m, 7H), 7.74 (m, 1H), 8.01 (s, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.30 (s, 1H).

Example 4

Preparation of N-(3-methylcarbamoylphenyl)-1-phenylcyclopentanecarboxamide (Compound No. 11 in Table 1)

[0092] Melting point: 147° C.

[0093] IR (KBr, cm−1): 3339, 3275, 1638, 1586, 1557, 1528.

[0094] NMR (DMSO-d6, &dgr;): 1.67 (m, 4H), 1.94 (m, 2H), 2.65 (m, 2H), 2.75 (d, J=4.5 Hz, 3H), 7.20-7.60 (m, 7H), 7.76 (d, J=7.2 Hz, 1H), 7.98 (s, 1H), 8.33 (d, J=4.5 Hz, 1H), 9.32 (s, 1H).

Example 5

Preparation of N-(3-methylcarbamoylphenyl)-3-fluorophenylacetamide (Compound No. 14 in Table 1)

[0095] Melting point: 147-148° C.

[0096] IR (KBr, cm−1): 3314, 1661, 1636, 1587, 1530.

[0097] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.2 Hz, 3H), 3.69(s, 2H), 7.08 (dd, J=5.7 Hz, 5.7 Hz, 1H), 7.14 (d, J=7.5 Hz, 2H), 7.38 (m, 2H), 7.47 (d, J=8.1 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 8.02 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.30 (s, 1H).

Example 6

Preparation of N-(3-methylcarbamoylphenyl-4-fluorophenylacetamide (Compound No. 15 in Table 1)

[0098] Melting point: 155-156° C.

[0099] IR (KBr, cm−1): 3293, 1657, 1634, 1588, 1535, 1512.

[0100] NMR (DMSO-d6, &dgr;): 2.76 (d, J=3.9 Hz, 3H), 3.65 (s, 2H), 7.15 (dd, J=9.0 Hz, 9.0 Hz, 2H), 7.25-7.41 (m, 3H), 7.47 (d, J=7.5 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H). 8.02 (s, 1H), 8.35 (d, J=3.9 Hz, 1H, 10.28 (s, 1H).

Example 7

Preparation of N-(3-methylcarbamoylphenyl)-2-chlorophenylacetamide (Compound No. 16 in Table 1)

[0101] Melting point: 211-212° C.

[0102] IR (KBr, cm−1): 3268, 1659, 1642, 1586, 1535.

[0103] NMR (DMSO-d6, &dgr;): 2.77 (d, J=3.6 Hz, 3H), 3.85 (s, 2H), 7.25-7.55 (m, 6H), 7.74 (d, J=7.5 Hz, 1H), 8.04 (s, 1H), 8.36 (d, J=3.6 Hz, 1H), 10.34 (s, 1H).

Example 8

Preparation of N-(3-methylcarbamoylphenyl)-4-chlorophenylacetamide (Compound No. 18 in Table 1)

[0104] Melting point: 163-164° C.

[0105] IR (KBr, cm−1): 3279, 1663, 1640, 1588, 1535.

[0106] NMR (DMSO-d6, &dgr;): 2.76 (d, J=3.9 Hz, 3H), 3.66 (s, 2H), 7.35-7.42 (m, 5H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.02 (dd, J=1.5 Hz, 1.5 Hz, 1H), 8.36 (d, J=3.9 Hz, 1H), 10.30 (s, 1H.

Example 9

Preparation of N-(3-carbamoylphenyl)-3-bromophenylacetamide (Compound No. 20 in Table 1)

[0107] Melting point: 202° C.

[0108] IR (KBr, cm−1): 3378, 3295, 1659, 1624, 1586, 1534.

[0109] NMR (DMSO-d6, &dgr;): 3.67 (s, 2H), 7.20-7.60 (m, 7H), 7.76 (d, J=9.3 Hz, 1H), 7.94 (s, 1H), 8.03(s, 1H, 10.33 (s, 1H).

Example 10

Preparation of N-(3-methylcarbamoylphenyl)-3-bromophenylacetamide (Compound No. 22 in Table 1)

[0110] Melting point: 176-178° C.

[0111] IR (KBr, cm−1): 3324, 3254, 1642, 1591, 1554.

[0112] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.68 (s, 2H), 7.27-7.41 (m, 3H), 7.45-7.50 (m, 2H), 7.56 (s, 1H), 7.75 (d, J=8.0 Hz, 1H), 8.03 (s, 1H), 8.42 (d, J=4.5 Hz, 1H), 10.35 (s, 1H).

Example 11

Preparation of N-(3-dimethylcarbamoylphenyl)-3-bromophenylacetamide (Compound No. 23 in Table 1)

[0113] Melting point: 119-120° C.

[0114] IR (KBr, cm−1): 1678, 1613, 1588, 1557.

[0115] NMR (DMSO-d6, &dgr;): 2.90 (s, 3H), 2.96 (s, 8H), 3.68 (s, 2H), 7.06 (d, J=7.8 Hz, 1H), 725-7.41 (m, 3H), 7.47 (m, 1H), 7.53-7.60 (m, 2H), 7.68 (s, 1H), 10.30 (s, 1H).

Example 12

Preparation of N-(3-ethylcarbamoylphenyl)-3-bromophenylacetamide (Compound No. 24 in Table 1)

[0116] Melting point: 155° C.

[0117] IR (KBr, cm−1): 3329, 3268, 1665, 1640, 1549.

[0118] NMR (DMSO-d6, &dgr;): 1.11 (t, J=6.9 Hz, 3H), 3.29 m, 2H), 3.67 (s, 2H), 7.20-7.40 (m, 3H), 7.47 (d, J=8.1 Hz, 1H), 7.49 (d, J=8.1 Hz, 1H), 7.56 (s, 1H), 7.75 (d, J=8.4 Hz, 1H), 8.00 (s, 1H), 8.41 (t, J=5.1 Hz, 1H), 10.32 (s, 1H).

Example 13

Preparation of N-(3-(2hydroxyethyl)carbamoylphenyl)-3-bromophenylacetamide (Compound No. 28 in Table 1)

[0119] Melting point: 202° C.

[0120] IR (KBr, cm−1): 3407, 3358, 3279, 1671, 1640, 1589, 1539.

[0121] NMR (DMSO-d6, &dgr;): 3.26 (m, 2H), 3.47 (m, 2H), 3.65 (s 2H), 4.67 (t, J=5.7 Hz, 1H), 7.20-7.60 (m, 6H), 7.73 (d, J=7.2 Hz, 1H), 7.99 (s, 1H), 8.32 (m, 1H), 10.28 (s, 1H).

Example 14

Preparation of N-(3-hydroxycarbamoylphenyl)-3-bromophenylacetamide (Compound No. 29 in Table 1)

[0122] Melting point: 184-186° C. (decomposition)

[0123] IR (KBr, cm−1): 3314, 3231, 1663, 1632, 1582, 1535.

[0124] NMR (DMSO-d6, &dgr;): 3.68 (s 2H:, 7.25-7.60 (m, 6H), 7.75 (d, J=6.9 Hz, 1H), 7.98 (s, 1H), 9.01 (s, 1H, 10.33 (s, 1H), 11.12 (s, 1H).

Example 15

Preparation of N-(methoxycarbamoylphenyl)-3-bromophenylacetamide (Compound No. 30 in Table 1)

[0125] Melting point: 166° C.

[0126] IR (KBr, cm−1): 3299, 3187, 1659, 1611, 1595, 1560.

[0127] NMR (DMSO-d6, &dgr;): 3.69 (s, 5H), 7.22-7.60 (m, 6H), 7.77 (s, 1H, 8.00 (s, 1H), 10.37 (s, 1H), 11.69 (s, 1H).

Example 16

Preparation of N-(3-methylcarbamoylphenyl)-4-bromophenylacetamide (Compound No. 33 in Table 1)

[0128] Melting point: 165-166° C.

[0129] IR (KBr, cm−1): 3283, 1665, 1642, 1588, 1534.

[0130] NMR (DMSO-d6, &dgr;): 2.77 (d, J=4.5 Hz, 3H), 3.64 (s, 2H), 7.23-7.40 (m, 3H), 7.40-7.58 (m, 3H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.30 (s, 1H).

Example 17

Preparation of N-(3-methylcarbamoylphenyl)-3-methylphenylacetamide (Compound No. 42 in Table 1)

[0131] Melting point: 131° C.

[0132] IR (KBr, cm−1): 3299, 1659, 1634, 1586, 1530.

[0133] NMR (DMSO-d6, &dgr;): 2.29 (s, 3H), 2.76 (d, J=4.5 Hz, 3H), 3.60 (s, 2H), 7.06 (d, J=6.9 Hz, 1H, 7.09-7.22 (m, 3H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.02 (s, 1H), 8.35 (d, J=4.5 Hz, 1H), 10.26 (s, 1H).

Example 18

Preparation of N-(3-methylcarbamoylphenyl)-4-methylphenylacetamide (Compound No. 43 in Table 1)

[0134] Melting point: 174-175° C.

[0135] IR (KBr, cm−1): 3339, 3296, 1659, 1639, 1586, 1528.

[0136] NMR (DMSO-d6, &dgr;): 2.27 (s, 3H), 2.76 (d, J=4.5 Hz, 3H), 3.59 (s, 2H), 7.12 (d, J=8.1 Hz, 2H), 7.22 (d, J=8.1 Hz, 2H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.35 (d, J=1.5 Hz, 1H), 10.24 (s, 1H).

Example 19

Preparation of N-(3-methylcarbamoylphenyl)-3-methoxyphenylacetamide (Compound No. 59 in Table 1)

[0137] Melting point: 104-106° C.

[0138] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.60 (s, 2H), 3.73 (s, 3H), 6.81 (m, 1H), 6.89-6.92 (m, 2H), 7.23 (m, 2H, 7.36 (m, 1H), 7.47 (m, 1H), 7.76 (m, 1H), 8.02 (s, 1H), 8.38 (m, 1H), 10.28 (s, 1H).

Example 20

Preparation of N-(3-methylcarbamoylphenyl)-4-methoxyphenylacetamide (Compound No. 60 in Table 1)

[0139] Melting point: 155-157° C.

[0140] NMR (DMSO-6, &dgr;): 2.75 (d, J=4.5 Hz, 3H), 3.55 (s, 2H), 3.71 (s, 3H), 6.88 (d, J=8.8 Hz, 2H), 7.24 (d, J=8.8 Hz, 2H), 7.35 (m, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.8 Hz, 1H), 8.00 (s, 1H), 8.37 (m, 1H), 10.24 (s, 1H).

Example 21

Preparation of N-(3-methylcarbamoylphenyl)-3,4-dimethoxyphenylacetamide (Compound No. 61 in Table 1)

[0141] NMR (DMSO-d6, &dgr;): 2.75 (d, J=4.5 Hz, 3H), 3.55 (s, 2H), 3.71 (s, 3H), 3.73 (s, 3H), 6.82-6.94 (m, 3H), 7.35 (m, 1H), 7.46 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.00 (s, 1H), 8.37 (m, 1H), 10.22 (s, 1H).

Example 22

Preparation of N-(3-methylcarbamoylphenyl)-3,5-dimethoxyphenylacetamide (Compound No. 62 in Table 1)

[0142] Melting point: 146-147° C.

[0143] IR (KBr, cm−1): 3341, 3246, 1667, 1638, 1589, 1547.

[0144] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.2 Hz, 3H), 3.56 (s, 2H), 3.73 (s, 6H), 6.39 (s, 1H), 6.51 (s, 2H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.23 (s, 1H).

Example 23

Preparation of N-(3-methylcarbamoylphenyl)-3,4,5-trimethoxyphenylacetamide (Compound No. 63 in Table 1)

[0145] Melting point; 81-82° C.

[0146] IR (KBr, cm−1): 3304, 1642, 1589, 1554, 1508.

[0147] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.57 (s, 2H), 3.63 (s, 3H), 3.77 (s, 6H), 6.66 (s, 2H), 7.39 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 8.03 (s, 1H), 8.37 (d, J=4.5 Hz, 1H, 10.23 (s, 1H).

Example 24

Preparation of N-(3-methylcarbamoylphenyl)-3-benzyloxyphenylacetamide (Compound No. 68 in Table 1)

[0148] Melting point; 150° C.

[0149] IR (KBr, cm−1): 3302, 1661, 1634, 1586, 1530.

[0150] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.61 (s, 2H), 5.09 (s, 2H), 6.91 (dd, J=7.81 Hz, 7.8 Hz, 2H), 7.01 (s, 1H), 7.27 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.25-7.52 (m, 7H), 7.74 (d, J=7.8 Hz, 1H), 8.02 (s, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.27 (s, 1H).

Example 25

Preparation of N-(3-carbamoylphenyl)-3-hydroxyphenylacetamide (Compound No 71 in Table 1)

[0151] Melting point; 188-189° C.

[0152] NMR (DMSO-d6, &dgr;): 3.52 (s, 2H), 6.62 (m, 1H), 6.72-6.75 (m, 2H), 7.08 (m, 1H), 7.32-7.37 (m, 2H), 7.51 (d, J=6.9 Hz, 1H), 7.76 (d, J=7.8 Hz, 1H), 7.92 (1H), 8.02 (s, 1H), 9.34 (s, 1H), 10.25 (s, 1H).

Example 26

Preparation of N-(3-methylcarbamoylphenyl)-3-hydroxyphenylacetamide (Compound No. 72 in Table 1)

[0153] Melting point; 163° C.

[0154] IR (KBr, cm−1): 3333, 3293, 1676, 1640, 1588, 1562.

[0155] NMR (DMSO-d6, &dgr;): 2.74 (d, J=4.2 Hz, 3H), 3.53 (s, 2H), 6.61 (d, J=7.2 Hz, 1H), 6.72 (d, J=7.2 Hz, 1H), 6.74 (s, 1H), 7.08 (dd, J=7.2 Hz, 7.2 Hz, 1H), 7.34 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.73 (d, J=7.81 Hz, 1H), 7.80 (s, 1H), 8.34 (d, J=4.2 Hz, 1H), 9.30 (s, 1H), 10.22 (s, 1H).

Example 27

Preparation of N-(3-methylcarbamoylphenyl)-4-hydroxyphenylacetamide (Compound No. 73 in Table 1)

[0156] Melting point; 195-196° C.

[0157] IR (KBr, cm−1): 3393, 3283, 1661, 1638, 1541, 1518.

[0158] NMR (DMSO-d6, &dgr;): 2.73 (d, J=4.5 Hz, 3H), 3.48 (s, 2H), 6.68 (d, J=8.4 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 7.33 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.43 (d, J=8.71 Hz, 1H), 7.72 (d, J=7.8 Hz, 1H), 7.98 (s, 1H), 8.32 (d, J=4.5 Hz, 1H), 9.20 (s, 1H), 10.14 (s, 1H).

Example 28

Preparation of N-(3-methylcarbamoylphenyl)-3-methylcarbamoylphenyl)-3-nitrophenylacetamide (Compound No. 74 in Table 1)

[0159] Melting point 139° C.

[0160] IR (KBr, cm−1): 3322, 3250, 1665, 1640, 1666, 1524.

[0161] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.86 (s, 2H, 7.37 (dd, J=7.8 Hz, 7.8, Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.64 (dd, J=8.1 Hz, 8.1 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.1 Hz, 1H), 8.03 (s, 1H), 8.13 (d, J=8.1 Hz, 1H), 8.24 (s, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.39 (s, 1H).

Example 29

Preparation of N-(3-methylcarbamoylphenyl)-4-nitrophenylacetamide (Compound No. 75 in Table 1)

[0162] Melting point: 148-151° C.

[0163] IR (KBr, cm−1): 3277, 1663, 1640, 1588, 1522.

[0164] NMR (DMSO-d6, &dgr;): 2.74 (d, J=4.2 Hz, 3H), 3.83 (2H), 7.35 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (m, 1H), 7.60 (d, J=8.7 Hz, 2H), 7.72 (d, J=8.4 Hz, 1H), 8.00 (s, 1H), 8.19 (d, J=8.7 Hz, 2H, 8.33 (d, J=4.2 Hz, 1H, 10.36 (s, 1H).

Example 30

Preparation of N-(3-methylcarbamoylphenyl)-1-naphthylacetamide (Compound No. 113 in Table 1)

[0165] Melting point; 201-202° C.

[0166] IR (KBr, cm−1): 3274, 1657, 1640, 1588, 1532.

[0167] NMR (DMSO-d6, &dgr;): 2.75 (d, J=4.5 Hz, 3H), 4.16 (, 2H), 7.36 (dd, J=8.1 Hz, 8.1 Hz, 1H), 7.40-7.60 (m, 5H), 7.74 (d, J=7.8 Hz, 1H), 7.84 (d, J=7.8 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 8.03 (s, 1H), 8.35 (d, J=7.8 Hz, 1H), 8.37 (d, J=4.5 Hz, 1H), 10.44 (s, 1H).

Example 31

Preparation of N-(3-methylcarbamoylphenyl)-2-naphthylacetamide (Compound No. 114 in Table 1)

[0168] Melting point: 175-176° C.

[0169] IR (KBr, cm−1): 3393, 1655, 1634, 1588, 1530.

[0170] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.83 (s, 2H), 7.37 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.40-7.55 (m, 4H), 7.77 (d, J=8.4 Hz, 1H), 7.81-7.96 (m, 4H), 8.04 (s, 1H), 8.36 (d, J=4.1 Hz, 1H), 10.37 (s, 1H).

Example 32

Preparation of N-(3-methylcarbamoylphenyl)-3-indolylacetamide (Compound No. 140 in Table 1)

[0171] Melting point: 168-169° C.

[0172] IR (KBr, cm−1): 3382, 3287, 1655, 1636, 1588, 1555, 1528.

[0173] NMR (DMSO-d6, &dgr;): 2.73 (d, J=4.5 Hz, 3H), 3.72 (s, 2H), 6.96 (dd, J=7.5 Hz, 7.5 Hz, 1H), 7.05 (dd, J=7.81 Hz, 7.8 Hz, 1H), 7.24 (s, 1H), 7.27-7.38 (m, 2H), 7.43 (d, J=7.8 Hz, 1H), 7.59 (d, J=7.8 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 8.00 (s, 1H), 8.32 (d, J=4.5 Hz, 1H), 10.18 (s, 1H), 10.88 (s, 1H).

Example 33

Preparation of N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide (Compound No. 146 in Table 1)

[0174] Melting point; 194° C.

[0175] IR (KBr, cm−1): 3285, 1663, 1636, 1588, 1532.

[0176] NMR (DMSO-d6, &dgr;): 2.75 (d, J=4.2 Hz, 3H), 3.94 (s, 2H), 7.32-7.53 (4H), 7.61 (s, 1H), 7.76 (d, J=6.9 Hz, 1H), 7.91 (d, J=7.2 Hz, 1H), 7.98 (d, J=7.2 Hz, 1H), 8.04 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.40 (s, 1H).

Example 34

Preparation of N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide (Compound No. 148 in Table 1)

[0177] Melting point: 192° C.

[0178] IR (KBr, cm−1): 3295, 1676, 1632, 1595, 1559.

[0179] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.2 Hz, 3H), 4.03 (s, 2H), 7.30-7.41 (m, 3H), 7.47 (d, J=7.8 Hz, 1H), 7.65 (d, J=5.4 Hz, 1H), 7.75 (d, J=6.3 Hz, 1H), 7.77 (d, J=5.4 Hz, 1H), 7.91 (m, 1H), 8.02 (s, 1H), 8.35 (d, J=4.2 Hz, 1H), 10.39 (s, 1H).

Example 35

Preparation of N-(3-methylcarbamoylphenyl)-2,2-dimethyl-2,3-dihydro-5-benzofuranylacetamide (Compound No. 157 in Table 1)

[0180] Melting point; 92-93° C.

[0181] IR (KBr, cm−1): 3289, 1665, 1611, 1589, 1555

[0182] NMR (DMSO-6, &dgr;): 1.39 (s, 6H), 1.53 (s, 1H), 2.75 (d, J=4.5 Hz, 3H), 2.99 (s, 2H), 6.65 (d, J=8.4 Hz, 1H), 7.05 (d, J=8.1 Hz, 1H), 7.18 (s, 1H), 7.34 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.5 Hz, 1H), 7.80 (d, J=7.8 Hz, 1H), 8.02 (s, 1H), 8.33 (d, J=4.5 Hz, 1H, 9.18 (s, 1H).

Example 36

Preparation of N-(3-methylcarbamoylphenyl)-3,4-methylenedioxyphenyl-acetamide (Compound No. 159 in Table 1)

[0183] Melting point: 174-175° C.

[0184] IR (KBr, cm−1): 3337, 3291, 1659, 1634, 1586, 1530, 1505.

[0185] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.55 (s, 2H), 5.98 (s, 2H), 6.74-6.93 (m, 3H), 7.36 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 8.35 (d, J=4.5 Hz, 1H), 10.20 (s, 1H).

Example 37

Preparation of N-(3-methylcarbamoylphenyl)phenoxyacetamide (Compound No. 176 in Table 1)

[0186] Melting point: 131° C.

[0187] IR (KBR, cm−1): 3378, 3283, 1669, 1640, 1588, 1535.

[0188] NMR DMSO-d6, &dgr;): 2.75 (d, J=4.5 Hz, 3H), 4.69 (s, 2H), 6.63-7.01 (m, 3H), 7.22-7.40 (m, 3H), 7.60 (d, J=7.8 Hz, 1H), 7.77 (d, J=7.8 Hz, 1H), 8.05 (s, 1H), 8.36 (d, J=4.5 Hz, 1H), 10.18 (s, 1H.

Example 38

Preparation of N-(3-methylcarbamoylphenyl)-2-chlorophenoxyacetamide (Compound No. 177 in Table 1)

[0189] Melting point: 172-173° C.

[0190] IR KBr, cm−1): 3385, 3297, 1688, 1640, 1591, 1549.

[0191] NMR (DMSO-d6, &dgr;): 2.77 (d, J=4.5 Hz, 3H), 4.85 (s, 2H), 6.99 (dd, J=7.5 Hz, 7.5 Hz, 1H), 7.08 (d, J=8.1 Hz, 1H), 7.30 (dd, J=7.5 Hz, 7.5 Hz, 1H), 7.38-7.60 (m, 3H), 7.76 (d, J=8.4 Hz, 1H), 8.06 (s, 1H), 8.42 (d, J=4.5 Hz, 1H), 10.31 (s, 1H).

Example 39

Preparation of N-(3-methylcarbamoylphenyl)-2-methylphenoxyacetamide (Compound No. 183 in Table 1)

[0192] Melting point: 148° C.

[0193] IR (KBr, cm−1): 3399, 3285, 1696, 1640, 1547.

[0194] NMR (DMSO-d6, &dgr;): 2.24 (s, 3H), 2.75 (d, J=4.5 Hz, 3H), 4.70 (s, 2H), 6.80-6.90 (m, 2H), 7.07-7.19 (m, 2H), 7.37 (dd, J=8.1 Hz, 7.8 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.75 (d, J=8.1 Hz, 1H), 8.05 (s, 1H), 8.35 (d, J=4.5 Hz, 1H), 10.14 (s, 1H).

Example 40

Preparation of N-(3-methylcarbamoylphenyl)-2-methoxyphenoxyacetamide (Compound No. 187 in Table 1)

[0195] Melting point: 133° C.

[0196] IR (KBr, cm−1): 3385, 3268, 1690, 1638, 1591, 1547.

[0197] NMR (DMSO-d6, &dgr;): 2.76 (d, J=4.5 Hz, 3H), 3.79 (s, 3H), 4.66 (s, 2H), 6.82-7.02 (m, 4H), 7.38 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H, 8.05 (s, 1H), 8.38 (d, J=4.5 Hz, 1H), 10.18 (s, 1H).

Example 41

Preparation of N-(3-methylcarbamoylphenyl)-1-naphthyloxyacetamide (Compound No. 191 in Table 1)

[0198] Melting point: 194° C.

[0199] IR (KBr, cm−1): 3405, 3304, 1696, 1638, 1541.

[0200] NMR (DMSO-d6, &dgr;): 2.75 (d, J=4.2 Hz, 3H), 4.92 (s, 2H), 6.92 (d, J=7.8 Hz, 1H, 7.33-7.62 (m, 6H), 7.79 (d, J=8.1 Hz, 1H), 7.88 (m, 1H), 8.08 (s, 1H), 8.31 (m, 1H), 8.41 (d, J=4.2 Hz, 1H), 10.36 (s, 1H).

Example 42

Preparation of N-(3-methylcarbamoylphenyl)-2-naphthyloxyacetamide (Compound No. 192 in Table 1)

[0201] Melting point: 174° C.

[0202] IR (KBr, cm−1): 3382, 3275, 1672, 1638, 1588, 1557, 1534.

[0203] NMR (DMSO-d6, &dgr;): 2.75 (d, J=4.5 Hz, 3H), 4.82(s, 2H), 7.22-7.58 (m, 6H), 7.78-7.95 (m, 1H), 8.09 (s, 1H), 8.40 (d, J=4.5 Hz, 1H), 10.28 (s, 1H).

Example 43

Preparation of N-(3-methylcarbamoylphenyl)-2,3-dichlorophenoxyacetamide (Compound No. 204 in Table 1)

[0204] Melting point: 192-193° C.

[0205] IR (KBr, cm−1): 3385, 3291, 1692, 1644, 1547.

[0206] NMR (DMSO-d6, &dgr;): 2.77 (d, J=4.5 Hz, 3H), 4.91 (s, 2H), 7.08 (d, J=8.1 Hz, 1H), 7.20-7.45 (m, 3H), 7.52 (d, J=7.8 Hz, 1H), 7.74 (d, J=8.7 Hz, 1H), 8.05 (s, 1H), 8.42 (d, J=4.5 Hz, 1H), 10.34 (s, 1H).

Example 44

Preparation of N-(3-methylcarbamoylphenyl)-2-methyl-1-naphthylacetamide (Compound No. 216 in Table 1)

[0207] Melting point: 230-231° C.

[0208] IR (KBr, cm−1): 3299, 3071, 1684, 1638, 1589, 1560.

[0209] NMR (DMSO-d6, &dgr;): 2.50 (s, 3H), 2.73 (d, J=4.5 Hz, 3H), 4.21 (s, 2H), 7.22-7.55 (m, 5H), 7.65-7.78 (m, 2H), 7.85 (d, J=7.8 Hz, 1H, 8.01-8.15 (m, 2H), 8.36 (d, J=4.5 Hz, 1H), 10.50 (s, 1H).

Example 45

Preparation of N-(3-methylcarbamoylphenyl)-2-hydroxy-1-naphthylacetamide (Compound No. 219 in Table 1)

[0210] Melting point: 229-230° C.

[0211] IR (KBr, cm−1): 3310, 1686, 1613, 1582, 1561.

[0212] NMR (DMSO-d6, &dgr;): 2.75 (d, J=4.2 Hz, 3H), 4.11 (s, 2H), 7.19 (d, J=9.0 Hz, 1H), 7.20-7.50 (m, 4H), 7.66-7.82 (m, 3H), 7.87 (d, J=8.4 Hz, 1H), 8.04 (s, 1H), 8.37 (d, J=4.5 Hz, 9.79 (s, 1H), 10.32 (s, 1H).

Example 46

Preparation of N-(3-methylcarbamoylphenyl)-3-phenylpropionamide (Compound No. 233 in Table 1)

[0213] Melting point: 142-143° C.

[0214] IR (KBr, cm−1): 3295, 1657, 1613, 1593, 1545.

[0215] NMR (DMSO-d6, &dgr;): 2.62 (t, J=7.8 Hz, 2H), 2.75 (d, J=4.5 Hz, 3H), 2.90 (t, J=7.8 Hz, 2H), 7.10-7.40 (m, 6H), 7.44 (d, J=7.5 Hz, 1H), 7.72 (d, J=7.5 Hz, 1H), 7.99 (s, 1H), 8.33 (d, J=4.5 Hz, 1H), 10.00 (s, 1H).

Example 47

Preparation of N-(3-methylcarbamoylphenyl)-3-(2-methylphenyl)propionamide (Compound No. 240 in Table 1)

[0216] Melting point: 131° C.

[0217] IR (KBr, cm−1): 3289, 1674, 1640, 1555.

[0218] NMR (DMSO-d6, &dgr;): 2.29 (s, 3H), 2.57 (t, J=7.8 Hz, 2H, 2.75 (d, J=4.2 Hz, 3H), 2.88 (t, J=7.8 Hz, 2H), 7.02-7.18 (m, 4H), 7.34 (dd, J=7.8 Hz, 7.2 Hz, 1H), 7.44 (d, J=7.2 Hz, 1H), 7.73 (d, J=7.8 Hz, 1H), 7.98 (s, 1H), 8.33 (d, J=4.2 Hz, 1H), 10.01 (s, 1H)

Example 48

Preparation of N-(3-methylcarbamoylphenyl)-3-(4-hydroxyphenyl)propionamide (Compound No. 245 in Table 1)

[0219] Melting point: 158° C.

[0220] IR (KBr, cm−1): 3424, 3285, 1647, 1553.

[0221] NMR (DMSO-d6, &dgr;): 2.54 (t, J=7.8 Hz, 2H), 2.74 (d, J=4.2 Hz, 3I), 2.78 (t, J=7.8 Hz, 2H), 6.64 (d, J=8.1 Hz, 2H), 7.01 (d, J=8.1 Hz, 2H), 7.33 (dd, J=8.1 Hz, 7.5 Hz, 1H), 7.43 (d, J=7.5 Hz, 1H), 7.71 (d, J=8.1 Hz, 1H), 7.98 (s, 1H), 8.32 (d, J=4.2 Hz, 1H), 9.10 (s, 1H), 9.97 (s, 1H).

Example 49

Preparation of N-(3-methylcarbamoylphenyl)-3-(2-methoxyphenyl)propionamide (Compound No. 246 in Table 1)

[0222] Melting point: 150° C.

[0223] IR (KBr, cm−1): 3297, 1658, 1644, 1550.

[0224] NMR (DMSO-d6, &dgr;): 2.56 (t, J=7.2 Hz, 2H), 275 (d, J=3.9 Hz, 3H), 2.85 (t, J=7.2 Hz, 2H), 3.78 (s, 3H), 6.84 (dd, J=7.5 Hz, 7.5 Hz, 1H), 6.93 (d, J=7.5 Hz, 1H), 7.05-7.20 (m, 2H), 7.26 (dd, J=8.1 Hz, 8.1 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.99 (s, 1H), 8.38 (d, J=3.9 Hz, 1H), 9.67 (s, 1H).

Example 50

Preparation of N-(3-methylcarbamoylphenyl)-3-(4-methoxyphenyl)propionamide (Compound No. 248 in Table 1)

[0225] Melting point: 151-152° C.

[0226] IR (KBr, cm−1): 3289, 1669, 1634, 1613, 1557, 1514.

[0227] NMR (DMSO-d6, &dgr;): 2.57 (t, J=7.5 Hz, 2H), 2.77 (d, J=4.2 Hz, 3H), 2.85 (t, J=7.5 Hz, 2H), 3.71 (s, 3H), 6.84 (d, J=8.1 Hz, 2H), 7.16 (d, J=8.1 Hz, 2H), 7.35 (dd, J=7.8 Hz, 7.8 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.5 Hz, 1H), 8.01 (s, 1H), 8.34 (d, J=4.2 Hz, 1H), 10.00 (s, 1H).

Example 51

Preparation of N′-methyl-3-(4-methylbenzyloxycarbonylamino)benzamide (Compound No.51 in Table 2)

[0228] 4-Methylbenzylalcohol (307 mg) and di(N-succinimidyl)carbonate (966 mg) were dissolved in methylene chloride (20 ml), and triethylamine (0.70 ml) was added to the solution. After stirring for 4 hours at room temperature, water was added and an aqueous layer was extracted with methylene chloride. The extracted aqueous layer was successively washed with an aqueous saturated sodium chloride solution, an aqueous saturated sodium bicarbonate solution, an aqueous saturated sodium chloride solution, 2N hydrochloric acid, and an aqueous saturated sodium chloride solution, and dried over magnesium sulfate. After removing magnesium sulfate by filtration, the filtrate was concentrated to obtain N-(4-methylbenzyloxycarbonyloxy)succinate imide (664 mg) as an intermediate.

[0229] N-(4-methylbenzyloxycarbonyloxy)succinate imide (610 mg of the above-obtained product) was dissolved in dimethylformamide (2 ml), and 3-aminobenzoylmethyamide (313 mg) and triethylamine (0.32 ml) were added thereto. After stirring overnight at room temperature, the obtained insoluble material was added to water (15 ml) while the insoluble products are being filtered. The crystals obtained from filtrate was filtered and washed with water to obtain crude crystals. The crude crystals were dried and added to ethyl acetate (8 ml), and was heated under reflux for 10 minutes. The mixture was cooled to room temperature, and the crystals were collected by filtration and washed with ethyl acetate to obtain the desired compound (167 mg, yield 27%).

[0230] Melting Point: 167-168° C.

[0231] IR(KBr,cm−1): 3322,1738,1622,1557.

[0232] NMR(DMSO-d6, &dgr;): 2.28(s,3H), 2.74(d,J=4.6 Hz,3H), 5.09(s,2H), 7.17(d,J=7.9 Hz,2H), 7.23-7.42(m,4H), 7.54(d,J=6.5 Hz,1H), 7.91(s, 1H), 8.31(d,J=4.6 Hz, 1H), 9.82(s,1H).

[0233] In similar manners to the method of Example 51, compounds of Example 52-68 and Example 72 were prepared. Their physicochemical properties are set out below.

Example 52

Preparation of N′-methyl-3-(2-fluorobenzyloxycarbonylamino)benzamide (Compound No.17 in Table 2)

[0234] Melting Point: 189-190° C.

[0235] IR(KBr,cm−1): 3341,3291,1730,1622,1557.

[0236] NMR(DMSO-d6, &dgr;): 2.76(d,J=4.2 Hz,3H), 5.22(s,2H, 7.20-7.45(m,5H), 7.50-7.60(m,2H), 7.94(s,1H), 8.36(d,J=4.2 Hz,1H), 9.93(s,1H).

Example 53

Preparation of N′-methyl-3-(4-fluorobenzyloxycarbonylamino)benzamide (Compound No.21 in Table 2)

[0237] Melting Point; 153° C.

[0238] IR(KBr,cm−1): 3304,1732,1626,1613,1559.

[0239] NMR(DMSO-d6, &dgr;): 2.76(d, J=3.4 Hz,3H), 5.15(s,2H), 7.23(dd,J=8.6 Hz,8.6 Hz,2H), 7.35(dd,J=7.7 Hz,7.4 Hz, 1H), 7.42(d,J=7.4 Hz,1H), 7.49(dd,J=8.6 Hz,8.6 Hz,2H), 7.57(d,J=7.7 Hz, 1H), 7.94(s, 1H), 8.36(d,J=3.4 Hz, 1H), 9.90(s, 1H.

Example 54

Preparation of N′-methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide (Compound No.23 in Table 2)

[0240] Melting Point: 168° C.

[0241] IR(KBr,cm−1): 3329,3289,1728,1622,1559.

[0242] NMR(DMSO-d6, &dgr;): 2.74(d,J=4.4 Hz,3H, 5.23(s,2), 7.27-7.43(m,4H), 7.43-7.60(m,3H), 7.93(s, 1H), 8.30(d,J=4.4 Hz,1H), 9.94(s,1H).

Example 55

Preparation of N′-methyl-3-(4-chlorobenzyloxycarbonylamino)benzamide (Compound No.27 in Table 2)

[0243] Melting Point: 155-156° C.

[0244] IR(KBr,cm−1): 3351,3299,1734,1624,1557.

[0245] NMR(DMSO-d6, &dgr;): 2.74(d,J=4.5 Hz,3H), 5.14(s,2H), 7.25-7.43(m,6H), 7.55(d,J=8.3 Hz,1H), 7.91(s,1H), 8.32(d,J=4.5 Hz,1H), 9.88(s,1H).

Example 56

Preparation of N′-methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide (Compound No.29 in Table 2)

[0246] Melting Point: 167-168° C.

[0247] IR(KBr,cm−1): 3401,3258,1744,1711,1649,1561.

[0248] NMR(DMSO-d6, &dgr;): 2.74(d,J=4.4 Hz,3H), 5.26(s,2H), 7.25-7.43(m,3H), 7.50-7.60(m,2H), 7.64(d,J=8.0 Hz,1H), 7.93(s, 1H), 8.32(d,J=4.4 Hz, 1H), 9.97(s,1H).

Example 57

Preparation of N′-methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide (Compound No.85 in Table 2)

[0249] Melting Point: 219-220° C.

[0250] IR(KBr,cm−1): 3380,3241,1717,1651,1562.

[0251] NMR(DMSO-d6, &dgr;): 2.74(d,J=4.3 Hz,3H), 5.35(s,2H), 7.25-7.60(m,6H), 7.92(s,1H), 8.35(d,J=4.3 Hz,1H), 9.92(s,1H).

Example 58

Preparation of N′-methyl-3-(2-bromobenzyloxycarbonylamino)benzamide (Compound No.41 in Table 2)

[0252] Melting Point: 163-164° C.

[0253] IR(KBr,cm−1): 3324,1728,1622,1559.

[0254] NMR(DMSO-d6, &dgr;): 2.73(d,J=4.0 Hz,3H), 5.19(s,2H, 7.24-7.75(m,7H), 7.93(s,1H), 8.35(d,J=4.0 Hz,1H), 9.98(s,1H).

Example 59

Preparation of N′-methyl-3-(2-methylbenzyloxycarbonylamino)benzamide (Compound No.47 in Table 2)

[0255] Melting Point: 163° C.

[0256] IR(KBr,cm−1): 3358,3312,1734,1622,1557.

[0257] NMR(DMSO-d6, &dgr;): 2.35(s,3H), 2.76(d,J=4.4 Hz,3H), 5.17(s,2H), 7.18-7.35(m,3H), 7.35-7.45(m,3H), 7.57(d,J=7.7 Hz,1H), 7.94(s,1H), 8.37(d,J=4.4 Hz,1H), 9.89(s,1H).

Example 60

Preparation of N′-methyl-3-(3-methylbenyloxycarbonylamino)benzamide (Compound No.49 in Table 2)

[0258] Melting Point: 155° C.

[0259] IR(KBr,cm−1): 3343,3279,1736,1624,1559.

[0260] NMR(DMSO-d6, &dgr;): 2.32(s,3H), 2.76(d,J=4.2 Hz,3H), 5.12(s,2H), 7.10-7.45(m,6H), 7.57(d,J=8.0 Hz,1H), 7.94(s,1H), 8.36 (d,J=4.2 Hz, 1H), 9.89(s,1H).

Example 61

Preparation of N′-methyl-3-(4-isopropylbenzyloxycarbonylamino)benzamide (Compound No.57 in Table 2)

[0261] Melting Point: 189-190° C.

[0262] IR(KBr,cm−1); 3380,3235,1709,1647,1561.

[0263] NMR(DMSO-d6, &dgr;): 1.19(d,J=6.8 Hz,6H), 2.76(d,J=3.9 Hz,3H), 2.88(m,1H), 5.12(s, 2H), 7.20-7.40(m,6H), 7.57(d,J=7.7 Hz,1H), 7.93(s,1H), 8.35(d,J=3.9 Hz,1H), 9.87(s,1H).

Example 62

Preparation of N′-methyl-3-(2-methoxybenzyloxycarbonylamino)benzamide (Compound No.61 in Table 2)

[0264] Melting Point: 173° C.

[0265] IR(KBr,cm−1): 3341,3266,1726,1624,1561.

[0266] NMR(DMSO-d6, &dgr;): 2.76(d,J=4.0 Hz,3H), 3.82(s,3H), 5.14(s, 2H), 6.99(dd,J=7.4 Hz,7.4 Hz, 1H), 7.04(d,J=8.2 Hz,1H), 7.28-7.42(m,4H), 7.56(d,J=8.2 Hz,1H), 7.94(s,1H), 8.36(d,J=4.0 Hz, 1H), 9.89(s,1H).

Example 63

Preparation of N′-methyl-3-(4-methoxybenzyloxycarbonylamino)benzamide (Compound No.65 in Table 2)

[0267] Melting Point: 158-159° C.

[0268] IR(KBr,cm−1): 3331,3295,1730,1613,1555.

[0269] NMR(DMSO-d6, &dgr;): 2.74(d,J=4.3 Hz,3H), 3.73(s,3H), 5.06(s,2H), 6.92(d,J=8.2 Hz,2H), 7.20-7.40(m,4H), 7.54(d,J=7.7 Hz, 1H), 7.90(s,1H), 8.30(d,J=4.3 Hz, 1H), 9.78(s,1H).

Example 64

Preparation of N′-methyl-3-(4-chloro2-nitrobenzyloxycarbonylamino)benzamide (Compound No.77 in Table 2)

[0270] Melting Point: 193° C.

[0271] IR(KBr,cm−1): 3366,3248,1717,1624,1662,1537.

[0272] NMR(DMSO-d6, &dgr;): 2.76(d,J=3.3 Hz, 3H), 5.48(s, 2H, 7.36(dd,J=7.8 Hz,7.8 Hz, 1H), 7.44(d, J=7.8 Hz,1H), 7.58(d,J=7.8 Hz,1H), 7.77(d,J=8.1 Hz,1H), 7.90-7.98(m,2H), 8.23(s,1H), 8.35(d,J=3.3 Hz, 1H), 10.04(1H).

Example 65

Preparation of N′-methyl-3-(1-naphthylmethoxycarbonylamino)benzamide (Compound No.81 in Table 2)

[0273] Melting Point: 228-229° C.

[0274] IR(KBr,cm−1): 3353,3285,1730,1626,1555.

[0275] NMR(DMSO-d6, &dgr;): 2.76(d,J=4.4 Hz,3H), 5.64(s,2H), 7.30-7.45(m,2H), 7.50-7.70(m,5H, 7.90-8.03(m,3H), 8.12(d,J=7.6 Hz,1H), 8.38(d,J=4.4 Hz, 1H), 9.87(s,1H).

Example 66

Preparation of N′-methyl-3-(2-naphthylmethoxycarbonylamino)benzamide (Compound No. 89 in Table 2)

[0276] Melting Point: 157-158° C.

[0277] IR(KBr,cm−1): 3314,1699,1642,1589,1539.

[0278] NMR(DMSO-d6, &dgr;): 2.76(d,J=4.8 Hz,3H), 5.32(s,2H), 7.23-7.42(m,2H), 7.42-7.60(m,4H), 7.82-7.98(m,5H), 8.32(d,J=4.8 Hz, 1H), 9.90(s,1H).

Example 67

Preparation of N′-methyl-3-(5-fluorenylmethoxycarbonylamino)benzamide (Compound No.99 in Table 2)

[0279] Melting Point: 217° C.

[0280] IR(KBr,cm−1): 3349,3289,1730,1624,1586,1557.

[0281] NMR(DMSO-d6, &dgr;): 2.76(d,J=4.2 Hz,3H), 4.32(d,J=6.6 Hz,1H), 4.48(d,J=6.6 Hz,2H), 7.25-7.50(m, 6H), 7.59(m,1H), 7.76(d,J=7.2 Hz,2H), 7.92(d,J=7.2 Hz,2H), 7.93(s,1H, 8.37(d,J=4.2 Hz,1H), 9.87(s,1H).

Example 68

Preparation of N′-methyl-3-(phenoxycarbonylamino)benzamide(Compound No.181 in Table 2)

[0282] Melting Point: 193° C.

[0283] IR(KBr,cm−1): 3401,3268,1753,1624,1555.

[0284] NMR(DMSO-d6, &dgr;): 2.77(d,J=3.6 Hz,3H), 7.20-7.35(m, 3H), 7.35-7.45(m, 4H), 7.49(d,J=7.8 Hz, 1H), 7.63(s, 1H), 7.99(s,1H), 10.38(s,1H).

Example 69

Preparation of 1-(3-methylcarbamoylphenyl)-3-phenylurea(Compound No.182 in Table 2)

[0285] Phenylisocyanate (209 mg) and 3-aminobenzoylmethylamide (239 mg) were dissolved in dimethylformamide (2 ml. After starring for 6 hours at room temperature, dilute hydrochloric acid (15 ml) was added. The obtained crystals were filtered and washed with water to obtain crude crystals. The crude crystals were dried under reduced pressure and added to ethyl acetate (8 ml), and the mixture was heated under reflux for 10 minutes. The mixture was cooled to room temperature, and the crystals were collected by filtration and washed with ethyl acetate to obtain the desired compound (386 mg, yield 90%).

[0286] Melting Point: 209-210° C.

[0287] IR(KBr,cm−1): 3328,3279,1699,1626,1557.

[0288] NMR(DMSO-d6, &dgr;): 2.75(d,J=4.1 Hz,3H), 6.95(dd,J=7.3 Hz,7.3 Hz), 7.20-7.45(m,6H), 7.57(d,J=7.7 Hz,1H, 7.86(s,1H), 8.37(d,J=4.1 Hz, 1H), 8.67(s,1H), 8.79(s, 1H).

[0289] In similar manners to the method of Example 69, compounds of Example 70 and Example 71 were prepared Their physicochemical properties are set out below.

Example 70

Preparation of 3-benzyl-1-(3-methylcarbamoylphenyl)urea(Compound No.5 in Table 2)

[0290] Melting Point: 189-190° C.

[0291] IR(KBr,cm−1): 3366,3333,1640,1559.

[0292] NMR(DMSO-d6, &dgr;): 2.73(d,J=4.4 Hz,3H), 4.28(d,J=5.9 Hz,2H), 6.62(t,J=5.9 Hz,1H), 7.15-7.40(m,7H), 7.54(d,J=7.3 Hz, 1H), 7.79(s, 1H); 8.28(d,J=4.4 Hz, 1H), 8.66(s, 1H).

Example 71

Preparation of 3-benzyl-1-(3-methylcarbamoylphenyl)thiourea(Compound No.6 in Table 2)

[0293] Melting Point: 199° C.

[0294] IR(KBr,cm−1): 3343,2246,3069,1630,1584,1528

[0295] NMR(DMSO-d6, &dgr;): 2.76(d,J=4.5 Hz,3H), 4.72(d,J=5.4 Hz,2H), 7.20-7.40(m,6H), 7.45-7.60(m,2H), 7.81(s,1H), 8.20(s,1H), 8.36(d,J=4.5 Hz, 1H), 9.65(s,1H).

Example 72

Preparation of N′-methyl-3-(2-(2-methyl-5-nitro-1-imidazolyl) ethoxycarbonylamino)benzamide (Compound No.233 in Table 2)

[0296] Melting Point: 207° C.

[0297] IR(KBr,cm−1): 3362,1734,1636,1591,1533.

[0298] NMR(DMSO-d6, &dgr;): 2.48(s,3H), 2.76(d,J=4.2 Hz,3H), 4.47(t,J=4.8 Hz,2H), 1.61(t,J=4.8 Hz,2H), 7.34(dd,J=7.7 Hz,7.5 Hz,1H), 7.43(d,J=7.5 Hz,1H), 7.55(d,J=7.7 Hz,1H), 7.85(s,1H), 8.05(s,1H), 8.34(d,J=4.4 Hz,1H), 9.76(s, 1H)

Test Example 1

Measurement of anti-Helicobacter pylori activity

[0299] Brain heart infusion culture medium containing 10% fetal bovine serum (Difco) (5 ml) was taken in a test tube, and then the medium was inoculated with Helicobacter pylori strain 31A isolated from human (obtained from the Metropolitan Health Institute, Microorganism Department, First Laboratory of Bacteria). Cultivation was carried out under slightly aerobic condition (5% oxygen, 10% carbon dioxide, 85% nitrogen) at 37° C. for 48 hours with shaking.

[0300] The culture was then inoculated to brain heart infusion medium containing 10% fetal bovine serum at a ratio of 5%, and added with a test compound dissolved in 10% dimethyl sulfoxide. Cultivation was carried out under slightly aerobic condition at 37° C. for 48 hours with shaking, and then growth of Helicobacter pylori was examined. Antibacterial activity was recorded as the lowest concentration that exhibited growth inhibition (minimum inhibitory concentration: MIC). The results are shown in Tables 3 and 4. From the results shown in Tables 3 and 4, it can be understood that the compounds of the present invention have potent inhibitory activity against Helicobacter pylori. 3 TABLE 3 Example No. (Compound No. in Table 1) MIC (&mgr;g/ml)  1 (No. 17) 0.39  3 (No. 7) 1.56  8 (No. 18) 0.78 10 (No. 22) 0.39 16 (No. 33) 0.78 17 (No. 42) 0.39 18 (No. 43) 0.39 19 (No. 59) 0.78 20 (No. 60) 0.78 22 (No. 62) 1.56 23 (No. 63) 0.78 24 (No. 68) 0.78 30 (No.113) 0.10 31 (No. 114) 0.05 32 (No. 140) 0.78 33 (No. 146) 0.10 34 (No. 148) 0.20 36 (No. 159) 0.78 38 (No. 177) 0.78 41 (No. 191) 0.10 42 (No. 192) 0.39 43 (No. 204) 0.39 44 (No. 216) 0.78 45 (No. 219) 0.78 49 (No. 246) 0.78

[0301] 4 TABLE 4 Example No. (Compound No. in Table 2) MIC (&mgr;g/ml) 51 (No. 51) 0.10 52 (No. 17) 0.78 53 (No. 21) 0.78 54 (No. 23) 0.39 55 (No. 27) 0.20 56 (No. 29) 0.20 57 (No. 35) 0.20 58 (No. 41) 0.39 59 (No. 47) 0.39 60 (No. 49) 0.39 61 (No. 57) 0.78 62 (No. 61) 0.78 63 (No. 65) 0.78 65 (No. 81) 0.05 66 (No. 89) 0.10 70 (No. 5)  1.56

Test Example 2

Measurement of anti-Campylobacter jejuni activity

[0302] According to a similar method to that of Test Example 1, inhibitory activity of the compound of the present invention against Campylobacter jejuni was determined. As a result, MIC of the compound of Example 31 was 0.008 &mgr;g/ml. From the result, it can be understood that the compound of the present invention has potent inhibitory activity against Campylobacter jejuni.

Test Example 3

Acute toxicity test

[0303] The compound of the present invention, suspended in 0.5% CMC-Na aqueous solution, was forcibly administered orally to SD male and female rats, and symptoms of the rats were observed for seven days. As a result, each of LD50 values of the compounds of Examples 30 and 31 was not lower than 2,000 mg/kg.

Formulation Examples

[0304] (1) Tablet

[0305] The following ingredients were mixed according to a conventional method, and compressed to obtain a tablet by using a conventional apparatus. 5 Compound of Example 31 100 mg Crystalline cellulose 180 mg Corn starch 300 mg Lactose 600 mg Magnesium stearate  15 mg

[0306] (2) Soft capsule

[0307] The following ingredients were mixed according to a conventional method, and filled in a soft capsule. 6 Compound of Example 41 100 mg Olive oil 900 mg Lecithin  60 mg

[0308] Industrial Applicability

[0309] The amide derivatives of the present invention have potent antibacterial activity against Helicobacter pylori, and therefore, they are useful as an active ingredient of medicaments.

Claims

1. A compound represented by the following general formula (I):

372

wherein X represents R1(R2)(R3)C- where R1 represents a C3-C8 cycloakyl group, an optionally substituted C5-C14 aryl group, an optionally substituted heterocyclic residue wherein the heterocyclic residue is one of furan ring, dihydrofuran ring, tetrahydrofuran ring, pyran ring, dihydropyran ring, tetrahydropyran ring, benzofuran ring, dihydrobenzofuran ring, isobenzofuran ring, chromene ring, chroman ring, isochroman ring, thiophene ring, benzothiophene ring, pyrrole ring, pyrroline ring, pyrrolidine ring, imidazole ring, imidazoline ring, imidazolidine ring, pyrazole ring, pyrazoline ring, pyrazolidine ring, triazole ring, tetrazole ring, pyridine ring, pyridineoxide ring, piperidine ring, pyrazine ring, piperazine ring, pyrimidine ring, pyridazine ring, indoline ring, indole ring, indoline ring, isoindole ring, isoindoline ring, indazole ring, benzimidazole ring, purine ring, quinolizine ring, quinoline ring, phthalazine ring, naphthylidine ring, quinoxaline ring, quinazoline ring, cinnoline ring, pteridine ring, oxazole ring, oxazolidine ring, isoxazole ring, isoxazolidine ring, thiazole ring, thiazylidine ring, isothiazole ring, isothiazolidine ring, dioxane ring, dithian ring, morpholine ring, and thiomorpholine ring, an optionally substituted C6-C14 aryloxy group, or an optionally substituted C7-C15 arylmethyl group; R2 and R3 independently represent hydrogen atom or a C1-C5 alkyl group, or R2 and R3 may combine to represent a C2-C7 alkylene group; or

X represents R7-A- wherein R7 represents (i) a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group, an optionally substituted fluorenyl group or an optionally substituted heterocyclic group, (ii) an optionally substituted C6-C14 aryl group or (iii) an optionally substituted heterocyclic group, and A represents an oxygen atom or -N-R8 where R8 represents hydrogen atom or a C1-C5 alkyl group,

Y represents an oxygen atom or a sulfur atom,

R4 and R5 independently represent hydrogen atom or a C1-C5 alkyl group; and R6 represents hydrogen atom, a C1-C5 alkyl group which may optionally be substituted with a hydroxyl group, a hydroxyl group or a C1-C5 alkoxy group,

provided that the compounds wherein R7 is a benzyl group, A and Y are an oxygen atom, R4 and R6 are hydrogen atom, and R6 is a propyl group are excluded,

or a salt thereof, or a solvate thereof or a hydrate thereof.

2. The compound according to claim 1 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R4 is hydrogen atom.

3. The compound according to claim 1 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R5 is hydrogen atom.

4. The compound according to claim 3 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R6 is a C1-C5 alkyl group.

5. The compound according to claim 4 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R6 is methyl group.

6. The compound according to claim 1 or a salt thereof or a solvate thereof or a hydrate thereof, wherein Y is an oxygen atom.

7. The compound according to claim 6 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein X is R1(R2)(R3)C-.

8. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R2 and R3 are hydrogen atoms.

9. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R1 is a C6-C14 aryl group which may optionally be substituted.

10. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R1 is a residue of a heterocyclic compound which may optionally be substituted.

11. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R1 is a C6-C14 aryloxy group which may optionally be substituted.

12. The compound according to claim 7 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R1 is a C7-C15 arylmethyl group which may optionally be substituted.

13. The compound according to claim 1 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein X is R7-A-.

14. The compound according to claim 13 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein A is an oxygen atom or -N-H.

15. The compound according to claim 13 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R7 is a C1-C10 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group.

16. The compound according to claim 15 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R7 is a C1-C5 alkyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group.

17. The compound according to claim 16 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R7 is a methyl group which may optionally be substituted with an optionally substituted C6-C14 aryl group or an optionally substituted heterocyclic group.

18. The compound according to claim 17 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R7 is a methyl group which is substituted with an optionally substituted C6-C14 aryl group.

19. The compound according to claim 17 or a salt thereof, or a solvate thereof or a hydrate thereof, wherein R7 is a methyl group which is substituted with an optionally substituted heterocyclic group.

20. A compound selected from the group consisting of:

N-(3-methylcarbamoylphenyl)-3-chlorophenylacetamide;

N-(3-methylcarbamoylphenyl)-4-chlorophenylacetamide;

N-(3-methylcarbamoylphenyl)-3-bromophenylacetamide;

N-(3-methylcarbamoylphenyl)-4-bromophenylacetamide:

N-(3-methylcarbamoylphenyl)-3-methylphenylacetamide;

N-(3-methylcarbamoylphenyl)-4-methylphenylacetamide;

N-(3-methylcarbamoylphenyl)-3-methoxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-4-methoxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-3,4,5-trimethoxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-3-benzyloxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-1-naphthylacetamide;

N-(3-methylcarbamoylphenyl)-2-naphthylacetamide;

N-(3-methylcarbamoylphenyl)-3-inadolylacetamide;

N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide;

N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide;

N-(3-methylcarbamoylphenyl)-3,4-methylenedioxyphenylacetamide;

N-(3-methylcarbamoylphenyl)-2-chlorophenoxyacetamide;

N-(3-methylcarbamoylphenyl)-2,3-chlorophenoxyacetamide;

N-(3-methylcarbamoylpheny)-1-naphthyloxyacetamide;

N-(3-methylcarbamoylphenyl)-2-naphthyloxyacetimide; and

N-(3-methylcarbamoylphenyl)-3-(2-methoxyphenyl)propionamide,

or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

21. A compound selected from the group consisting of:

N′-methyl-3-(2-chlorobenzyloxycarbonylamino)benzamide,

N′-methyl-3-(4-chlorobenxyloxycarbonylamino)benzamide;

N′-methyl-3-(2,3-dichlorobenzyloxycarbonylamino)benzamide;

N′-methyl-3-(2,6-dichlorobenzyloxycarbonylamino)benzamide;

N′-methyl-3-(2-bromobenzyloxycarbonylamino)benzamide;

N′-methyl-3-(2-methylbenzyloxycarbonylamino)benzamide;

N′-methyl-3(3-methylbenzyloxycarbonylamino)benzamide;

N-methyl-3-(4-methylbenzyloxycarbonylamino)benzamide;

N′-methyl-3-(1-naphthylmethoxycarbonylamino)benzamide; and

N′-methyl-3-(2-naphthylmethoxycarbonylamino)benzamide;

or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

22. N-(3-methylcarbamoylpheny)-1-naphthylacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

23. N-(3-methylcarbamoylphenyl)-2-naphthylacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

24. N-(3-methylcarbamoylphenyl)-3-benzothienylacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

25. N-(3-methylcarbamoylphenyl)-4-benzothienylacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

26. N-(3-methylcarbamoylphenyl)-1-naphthyloxyacetamide or a pharmaceutically acceptable salt thereof, or a solvate thereof or a hydrate thereof.

27. A medicament comprising as an active ingredient a substance selected from the group consisting of a compound according to claim 1 and a salt thereof, and a solvate thereof and a hydrate thereof.

28. The medicament according to claim 27 which is in the form of a pharmaceutical composition comprising said substance as an active ingredient and one or more pharmaceutical additives.

29. The medicament according to claim 27 which has antibacterial activity.

30. The medicament according to claim 29 which has antibacterial activity against a microorganism belonging to the genus Helicobacter and/or Campylobacter.

31. The medicament according to claim 30 which has anti-Helicobacter pylori activity and/or anti-Campylobacter jejuni activity.

32. A process for at least one of preventing and treating a digestive disease, comprising administering the medicament according claim 27.

33. The process of claim 32, wherein the digestive disease is one of gastritis, gastric ulcer, gastric cancer, gastric malignant lymphoma, MALT lymphoma, duodenal ulcer, duodenal carcinoma, and enteritis.

34. A process for preventing recurrence of a digestive disease, comprising administering the medicament according to claim 27.

35. The process of claim 34, wherein the digestive disease is one of gastric ulcer and duodenal ulcer.