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.

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.

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, 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.

TABLE 3
Example No.
(Compound No. in Table 1) MIC (μg/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]

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.

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.

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):

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.