Amide derivatives

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


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.
1TABLE 1Compd.No.R1R2R3R4R5R613HHHHCH324HHHHCH335HHHHCH346HHHHCH357HHHHCH368HHHHCH379HHHHCH3810CH3HHHCH3911CH3CH3HHCH31012CH3CH3CH3HCH31113—(CH2)4HHCH31214—(CH2)5HHCH31315HHHHCH31416HHHHCH31517HHHHCH31618HHHHCH31719HHHHCH31820HHHHCH31921HHHHCH32022HHHHH2123HHCH3HCH32224HHHHCH32325HHHCH3CH32426HHHHCH2CH32527HHHHCH2CH2CH32628HHHH(CH2)3CH32729HHHH(CH2)4CH32830HHHHCH2CH2OH2931HHHHOH3032HHHHOCH33133HHHHOCH2CH33234HHHCH2CH3CH2CH33335HHHHCH33436HHHHCH33537HHHHCH33638HHHHCH33739HHHHCH33840HHHHCH33941HHHHCH34042HHHHCH34143HHHHCH34244HHHHCH34345HHHHCH34446HHHHCH34547HHHHCH34648HHHHCH34749HHHHCH34850HHHHCH34951HHHHCH35052HHHHCH35153HHHHCH35254HHHHCH35355HHHHCH35456HHHHCH35557HHHHCH35658HHHHCH35759HHHHCH35860HHHHCH35961HHHHCH36062HHHHCH36163HHHHCH36264HHHHCH36365HHHHCH36466HHHHCH36567HHHHCH36668HHHHCH36769HHHHCH36870HHHHCH36971HHHHCH37072HHHHCH37173HHHHH7274HHHHCH37375HHHHCH37476HHHHCH37577HHHHCH37678HHHHCH37779HHHHCH37880HHHHCH37981HHHHCH38082HHHHCH38183HHHHCH38284HHHHCH38385HHHHCH38486HHHHCH38587HHHHCH38688HHHHCH38789HHHHCH38890HHHHCH38991HHHHCH39092HHHHCH39193HHHHCH39294HHHHCH39395HHHHCH39496HHHHCH39597HHHHCH39698HHHHCH39799HHHHCH398100HHHHCH399101HHHHCH3100102HHHHCH3101103HHHHCH3102104HHHHCH3103105HHHHCH3104106HHHHCH3105107HHHHCH3106108HHHHCH3107109HHHHCH3108110HHHHCH3109111HHHHCH3110112HHHHCH3111113HHHHCH3112114HHHHCH3113115HHHHCH3114116HHHHCH3115117HHHHCH3116118HHHHCH3117119HHHHCH3118120HHHHCH3119121HHHHCH3120122HHHHCH3121123HHHHCH3122124HHHHCH3123125HHHHCH3124126HHHHCH3125127HHHHCH3126128HHHHCH3127129HHHHCH3128130HHHHCH3129131HHHHCH3130132HHHHCH3131133HHHHCH3132134HHHHCH3133135HHHHCH3134136HHHHCH3135137HHHHCH3136138HHHHCH3137139HHHHCH3138140HHHHCH3139141HHHHCH3140142HHHHCH3141143HHHHCH3142144HHHHCH3143145HHHHCH3144146HHHHCH3145147HHHHCH3146148HHHHCH3147149HHHHCH3148150HHHHCH3149151HHHHCH3150152HHHHCH3151153HHHHCH3152154HHHHCH3153155HHHHCH3154156HHHHCH3155157HHHHCH3156158CH3HHHCH3157159CH3CH3HHCH3158160HHHHCH3159161HHHHCH3160162HHHHCH3161163HHHHCH3162164HHHHCH3163165HHHHCH3164166HHHHCH3165167HHHHCH3166168HHHHCH3167169HHHHCH3168170HHHHCH3169171HHHHCH3170172HHHHCH3171173HHHHCH3172174HHHHCH3173175HHHHCH3174176HHHHCH3175177HHHHCH3176178HHHHCH3177179HHHHCH3178180HHHHCH3179181HHHHCH3180182HHHHCH3181183HHHHCH3182184HHHHCH3183185HHHHCH3184186HHHHCH3185187HHHHCH3186188HHHHCH3187189HHHHCH3188190HHHHCH3189191HHHHCH3190192HHHHCH3191193HHHHCH3192194HHHHCH3193195HHHHCH3194196HHHHCH3195197HHHHCH3196198HHHHCH3197199HHHHCH3198200HHHHCH3200201HHHHCH3201202HHHHCH3202203HHHHCH3203204HHHHCH3204205HHHHCH3205206HHHHCH3206207HHHHCH3207208HHHHCH3208209HHHHCH3209210HHHHCH3210211HHHHCH3211212HHHHCH3212213HHHHCH3213214HHHHCH3214215HHHHCH3215216HHHHCH3216217HHHHCH3217218HHHHCH3218219HHHHCH3219220HHHHCH3220221HHHHCH3221222HHHHCH3222223HHHHCH3223224HHHHCH3224225HHHHCH3225226HHHHCH3226227HHHHCH3227228HHHHCH3228229HHHHCH3229230HHHHCH3230231HHHHCH3231232HHHHCH3232233HHHHCH3233234HHHHCH3234235HHHHCH3235236HHHHCH3236237HHHHCH3237238HHHHCH3238239HHHHCH3239240HHHHCH3240241HHHHCH3241242HHHHCH3242243HHHHCH3243244HHHHCH3244245HHHHCH3245246HHHHCH3246247HHHHCH3247248HHHHCH3248249HHHHCH3249250HHHHCH3250251HHHHCH3251252HHHHCH3252253HHHHCH3


[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.
2TABLE 2Compd.No.R7AYR4R5R6 1CH3OOHHCH3 2NHO 3  4  5  6254O O NH NHO S O SHHCH3 7  8255O NHO OHHH 9  10256O NHO OHCH3CH3 11  12257O NHO OHHCH2CH3 13  14258O NHO OHHCH2CH2CH3 15  16259O NHO OCH3HCH3 17  18260O NHO OHHCH3 19  20261O NHO OHHCH3 21  22262O NHO OHHCH3 23  24263O NHO OHHCH3 25  26264O NHO OHHCH3 27  28265O NHO OHHCH3 29  30266O NHO OHHCH3 31  32267O NHO OHHCH3 33  34268O NHO OHHCH3 35  36269O NHO OHHCH3 37  38270O NHO OHHCH3 39  40271O NHO OHHCH3 41  42272O NHO OHHCH3 43  44273O NHO OHHCH3 45  46274O NHO OHHCH3 47  48275O NHO OHHCH3 49  50276O NHO OHHCH3 51  52277O NHO OHHCH3 53  54278O NHO OHHCH3 55  56279O NHO OHHCH3 57  58280O NHO OHHCH3 59  60281O NHO OHHCH3 61  62282O NHO OHHCH3 63  64283O NHO OHHCH3 65  66284O NHO OHHCH3 67  68285O NHO OHHCH3 69  70286O NHO OHHCH3 71  72287O NHO OHHCH3 73  74288O NHO OHHCH3 75  76289O NHO OHHCH3 77  78290O NHO OHHCH3 79  80291O NHO OHHCH3 81  82292O NHO OHHCH3 83  84293O NHO OHHCH3 85  86294O NHO OHHCH3 87  88295O NHO OHHCH3 89  90296O NHO OHHCH3 91  92297O NHO OHHCH3 93  94298O NHO OHHCH3 95  96299O NHO OHHCH3 97  98300O NHO OHHCH3 99 100301O NHO OHHCH3101 102302O NHO OHHCH3103 104303O NHO OHHCH3105 106304O NHO OHHCH3107 108305O NHO OHHCH3109 110306O NHO OHHCH3111 112307O NHO OHHCH3113 114308O NHO OHHCH3115 116309O NHO OHHCH3117 118310O NHO OHHCH3119 120311O NHO OHHCH3121 122312O NHO OHHCH3123 124313O NHO OHHCH3125 126314O NHO OHHCH3127 128315O NHO OHHCH3129 130316O NHO OHHCH3131 132317O NHO OHHCH3133 134318O NHO OHHCH3135 136319O NHO OHHCH3137 138320O NHO OHHCH3139 140321O NHO OHHCH3141CH3CH2OOHHCH3142NHO143 144322O NHO OHHCH3145 146323O NHO OHHCH3147 148324O NHO OHHCH3149 150325O NHO OHHCH3151 152326O NHO OHHCH3153 154327O NHO OHHCH3155 156328O NHO OHHCH3157 158329O NHO OHHCH3159 160330O NHO OHHCH3161 162331O NHO OHHCH3163 164332O NHO OHHCH3165 166333O NHO OHHCH3167 168334O NHO OHHCH3169 170335O NHO OHHCH3171 172336O NHO OHHCH3173 174337O NHO OHHCH3175 176338O NHO OHHCH3177 178339O NHO OHHCH3179 180340O NHO OHHCH3181 182 183 184 185 186341O NH NCH3O NH NCH3O O O S S SHHCH3187 188342O NHO OHHH189 190343O NHO OHCH3CH3191 192344O NHO OHHCH2CH3193 194345O NHO OHHCH2CH2CH3195 196346O NHO OCH3HCH3197 198347O NHO OHHCH3199 200348O NHO OHHCH3201 202349O NHO OHHCH3203 204350O NHO OHHCH3205 206351O NHO OHHCH3207 208352O NHO OHHCH3209 210353O NHO OHHCH3211 212354O NHO OHHCH3213 214355O NHO OHHCH3215 216356O NHO OHHCH3217 218357O NHO OHHCH3219 220358O NHO OHHCH3221 222359O NHO OHHCH3223 224360O NHO OHHCH3225 226361O NHO OHHCH3227 228362O NHO OHHCH3229 230363O NHO OHHCH3231 232364O NHO OHHCH3233 234365O NHO OHHCH3235 236366O NHO OHHCH3237 238367O NHO OHHCH3239 240368O NHO OHHCH3


[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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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, δ): 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. 3TABLE 3Example No.(Compound No. in Table 1)MIC (μg/ml) 1 (No. 17)0.39 3 (No. 7)1.56 8 (No. 18)0.7810 (No. 22)0.3916 (No. 33)0.7817 (No. 42)0.3918 (No. 43)0.3919 (No. 59)0.7820 (No. 60)0.7822 (No. 62)1.5623 (No. 63)0.7824 (No. 68)0.7830 (No.113)0.1031 (No. 114)0.0532 (No. 140)0.7833 (No. 146)0.1034 (No. 148)0.2036 (No. 159)0.7838 (No. 177)0.7841 (No. 191)0.1042 (No. 192)0.3943 (No. 204)0.3944 (No. 216)0.7845 (No. 219)0.7849 (No. 246)0.78


[0301]

4








TABLE 4











Example No.




(Compound No. in Table 2)
MIC (μg/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 μg/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.
5Compound of Example 31100 mgCrystalline cellulose180 mgCorn starch300 mgLactose600 mgMagnesium stearate 15 mg


[0306] (2) Soft capsule


[0307] The following ingredients were mixed according to a conventional method, and filled in a soft capsule.
6Compound of Example 41100 mgOlive oil900 mgLecithin 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):
  • 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.
Priority Claims (1)
Number Date Country Kind
9-168484 Jun 1997 JP
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.

Divisions (1)
Number Date Country
Parent 09469354 Dec 1999 US
Child 10173076 Jun 2002 US
Continuation in Parts (1)
Number Date Country
Parent 09103500 Jun 1998 US
Child 09469354 Dec 1999 US