IP Library Granted Patent US 8,466,161
Granted Patent B2
US 8,466,161 · App. 13/258,630 · Granted Jun 18, 2013

Hydroxamate derivative, a production method for the same, and a pharmaceutical composition comprising the same

Inventors: Sung Sook Lee (Cheonan-si, KR); Kyung Joo Lee (Cheonan-si, KR); Chang Sik Lee (Cheonan-si, KR); Hyun Mo Yang (Cheonan-si, KR); Do Hoon Kim (Cheonan-si, KR); Dae Kyu Choi (Cheonan-si, KR); Ho Jin Choi (Cheonan-si, KR); Dal Hyun Kim (Cheonan-si, KR); In Chang Hwang (Cheonan-si, KR); Mi Jeong Kim (Cheonan-si, KR); Byeong Hoon Han (Cheonan-si, KR)
Assignee: Chong Kun Dang Pharmaceutical Corp.
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Quick Facts
Patent No.
US 8,466,161
App. No.
13/258,630
Granted
Jun 18, 2013
Kind
B2
Abstract

The present invention relates to hydroxamate compounds of the following formula I, an isomer, pharmaceutically acceptable salt or hydrate thereof. The present invention also relates to a method for preparing the hydroxamate compounds, comprising allowing a compound of the following formula II to react with bromoaniline in the presence of an inorganic salt so as to prepare a compound of the following formula III. Moreover, the invention relates to a method for treating specific diseases by administering the compositions containing the hydroxamate compounds

Claims (186)

1. A hydroxamate compound of the following formula I, an isomer, pharmaceutically acceptable salt or hydrate thereof,

wherein n is an integer of 2, 3 or 4;

Ar is a phenyl, pyridine or pyrimidine group which is unsubstituted or substituted with one or more substituents selected from the group consisting of C 1-6 alkyl, amino, nitro, thiomethyl, hydroxyl, nitrile, carboxyl, C 1-4 alkyloxy, aryl C 1-4 alkyloxy, halogen, trifluoromethyl, —O—CF 3 , phenyl and phenoxy groups;

R 1 is an indole, indazole or benzimidazole group, which is unsubstituted or substituted with one or more substituents selected from the groups consisting of C 1-6 alkyl, formyl, amino, nitro, thiomethyl, hydroxyl, C 1-6 alkoxy, nitrile, carboxyl, halogen, trifluoromethyl, —O—CF 3 , —C(O)—R 5 , —S(O 2 )—R 5 and

and

R 2 is hydrogen, hydroxy C 1-6 alkyl, C 1-8 alkyl, —C(O)—R 5 , —C(O)NH—R 5 , —S(O 2 )—R 5 , —C(S)—R 5 or —C(O 2 )—R 5 , in which R 5 is

naphthyl, C 1-8 alkyl or C 1-4 alkyloxy group, Z 1 and Z 2 are each independently hydrogen, C 1-6 alkyl, amino, —O—C 1-4 alkyl, —S(O 2 )C 1-4 alkyl, —C(O)C 1-4 alkyl, —S—C 1-4 alkyl, halogen, trifluoromethyl, —O—CF 3 , phenyl, —O-phenyl, —O—C 1-4 alkylaryl,

V and W are each independently hydrogen or C 1-6 alkyl,

Each s is independently an integer of 0, 1, 2, 3, 4 or 5, and

Each m is independently an integer of 0, 1, 2 or 3.

2. The hydroxamate compound of formula I, isomers thereof, pharmaceutically acceptable salts thereof, or hydrates thereof according to claim 1 , wherein R 1 is an indole or indazole group which is unsubstituted or substituted with one or more substituents selected from the group consisting of C 1-6 alkyl, formyl, amino, nitro, thiomethyl, hydroxy, C 1-6 alkoxy, nitrile, carboxy, halogen, trifluoromethyl, —O—CF 3 , —C(O)—R 5 , —S(O 2 )—R 5 and

3. The hydroxamate compound of formula I, isomers thereof, pharmaceutically acceptable salts thereof, or hydrates thereof according to claim 2 , wherein Ar is a phenyl group which is unsubstituted or substituted with one or more substituents selected from the group consisting of C 1-6 alkyl, amino, nitro, thiomethyl, hydroxyl, nitrile, carboxyl, C 1-4 alkyloxyl, aryl C 1-4 alkyloxy, halogen, trifluoromethyl, —O—CF 3 , phenyl and phenoxy groups.

4. The hydroxamate compound of formula I, isomers thereof, pharmaceutically acceptable salts thereof, or hydrates thereof according to claim 3 , wherein n is 3, Ar is an unsubstituted phenyl group, R 1 is an indole or indazole group which is substituted with hydrogen or one or more C 1-6 alkyl groups, and R 2 is hydrogen, —C(O)—R 5 or —S(O 2 )—R 5 , in which R 5 is

naphthyl, C 1-8 alkyl or C 1-4 alkyloxy group, Z 1 and Z 2 are each independently hydrogen, C 1-6 alkyl, amino, —O—C 1-4 alkyl, —S(O 2 )C 1-4 alkyl, —C(O)C 1-4 alkyl, —S—C 1-4 alkyl, halogen, trifluoromethyl, —O—CF 3 , phenyl, —O-phenyl, —O—C 1-4 alkylaryl,

V and W are each independently hydrogen or C 1-6 alkyl,

Each s is independently an integer of 0, 1, 2, 3, 4 or 5, and

Each m is independently an integer of 0, 1, 2 or 3.

5. The hydroxamate compound of formula I, isomers thereof, pharmaceutically acceptable salts thereof, or hydrates thereof according to claim 4 , wherein n is 3, Ar is an unsubstituted phenyl group, R 1 is an indole or indazole group which is substituted with hydrogen or one or more C 1-6 alkyl groups, and R 2 is hydrogen, —C(O)—R 5 or —S(O 2 )—R 5 , in which R 5 is

in which Z 2 is hydrogen or C 1-6 alkyl, and m is an integer of 0, 1, 2 or 3.

6. The hydroxamate compound, isomers thereof, pharmaceutically acceptable salts thereof, or hydrates thereof according to claim 1 , wherein the hydroxamate compound is selected from the group consisting of the following compounds:

7-(4-(1H-indol-5-yl)phenylamino)-N-hydroxyheptanamide;

N-hydroxy-7-(4-(1-methyl-1H-indol-5-yl)phenylamino)hydroxyheptanamide;

7-(3-(1H-indol-6-yl)phenylamino)-N-hydroxyheptanamide;

7-(4-(1H-indol-6-yl)phenylamino)-N-hydroxyheptanamide;

7-(3-(1H-indol-5-yl)phenylamino)-N-hydroxyheptanamide;

7-(4-(1H-indol-4-yl)phenylamino)-N-hydroxyheptanamide;

7-(2-(1H-indol-5-yl)phenylamino)-N-hydroxyheptanamide;

7-(5-(1H-indol-6-yl)pyridin-2-ylamino)-N-hydroxyheptanamide;

7-(6-(1H-indol-6-yl)pyridin-3-ylamino)-N-hydroxyheptanamide;

7-(3-(1H-indol-7-yl)phenylamino)-N-hydroxyheptanamide;

7-(5-(1H-indol-6-yl)pyrimidin-2-ylamino)-N-hydroxyheptanamide;

7-(4-(1H-indol-7-yl)phenylamino)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methoxybenzamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)nicotinamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-2-phenylacetamido)-N-hydroxyheptanamide;

phenyl 4-(1H-indol-6-yl)phenyl(7-(hydroxyamino)-7-oxoheptyl)carbamate;

benzyl 4-(1H-indol-6-yl)phenyl(7-(hydroxyamino)-7-oxoheptyl)carbamate;

7-((4-(1H-indol-6-yl)phenyl)(2-hydroxyethyl)amino)-N-hydroxyheptanamide;

N-hydroxy-7-(4-(1-(phenylsulfonyl)-1H-indol-2-yl)phenylamino)heptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)thiophene-2-sulfonamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)furan-2-carboxamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-4-methoxyphenylsulfonamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-5-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methoxybenzamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methylbenzamide;

7-(N-(4-(1H-indol-6-yl)phenyl)phenylsulfonamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)picolinamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-3-methoxybenzamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-3,4,5-trimethylbenzamide;

N-(4-(1H-indol-6-yl)phenyl)-4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-2-aminoacetamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-6-chloro-N-(7-(hydroxyamino)-7-oxoheptyl)nicotinamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)isonicotinamide;

(Z)-N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-(N′-hydroxycarbamimidoyl)benzamide;

N-(4-(1H-indol-6-yl)phenyl)-2,6-difluoro-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide;

N-(4-(1H-indol-6-yl)phenyl)-4-fluoro-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-6-(trifluoromethyl)nicotinamide;

6-(4-(1H-indol-6-yl)phenylamino)-N-hydroxyhexanamide;

8-(4-(1H-indol-6-yl)phenylamino)-N-hydroxyoctanamide;

N-(4-(1H-indol-6-yl)phenyl)-4-ethoxy-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide;

7-((4-(1H-indol-6-yl)phenyl)(benzyl)amino)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-2,4,6-trifluoro-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide;

N-(4-(1H-indol-6-yl)phenyl)-4-amino-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)piperidin-1-carboxamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methoxy-3-(trifluoromethyl)benzamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-(trifluoromethyl)benzamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-3,4-dimethoxybenzamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-3,4-dimethoxyphenylsulfonamido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-4-(methylsulfonyl)phenylsulfonamido)-N-hydroxyheptanamide;

7-(4-(1H-indol-6-yl)-3-(trifluoromethyl)phenylamino)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)-3-(trifluoromethyl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)nicotinamide;

7-(N-(4-(1H-indol-6-yl)phenyl)naphthalene-2-sulfonamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)-3-methylphenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methoxybenzamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(4-methoxyphenyl)ureido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(3-methoxyphenyl)ureido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)acetamido)-N-hydroxyheptanamide;

methyl 4-(1H-indol-6-yl)phenyl(7-(hydroxyamino)-7-oxoheptyl)carbamate;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(2-methoxyphenyl)ureido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(3,5-dimethoxyphenyl)ureido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-5-amino-2-methoxyphenylsulfonamido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(thiophen-2-yl)ureido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)pyridine-3-sulfonamido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)methylsulfonamido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-2-(dimethylamino)acetamido)-N-hydroxyheptanamide;

4-methoxyphenyl 4-(1H-indol-6-yl)phenyl(7-(hydroxyamino)-7-oxoheptyl)carbamate;

ethyl 4-(1H-indol-6-yl)phenyl(7-(hydroxyamino)-7-oxoheptyl)carbamate;

7-(1-(4-(1H-indol-6-yl)phenyl)-3,3-dimethylureido)-N-hydroxyheptanamide;

2-methoxyethyl 4-(1H-indol-6-yl)phenyl(7-(hydroxyamino)-7-oxoheptyl)carbamate;

N-(7-(hydroxyamino)-7-oxoheptyl)-N-(4-(1-methyl-1H-indazol-6-yl)phenyl)nicotinamide;

N-hydroxy-7-(4-(1-methyl-1H-indazol-6-yl)phenylamino)heptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)propionamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-1-methyl-1,2,5,6-tetrahydropyridine-3-carboxamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(pyridin-3-yl)ureido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-methylureido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)ethylsulfonamido)-N-hydroxyheptanamide;

7-((4-(1H-indol-6-yl)phenyl)(N,N-dimethylsulfamoyl)amino)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)cyclohexanecarboxamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)cyclopropanecarboxamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-2-morpholinoacetamido)-N-hydroxyheptanamide;

(S)—N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrrolidine-2-carboxamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-isopropylureido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-isobutylureido)-N-hydroxyheptanamide;

N-hydroxy-7-(N-(4-(1-methyl-1H-indazol-6-yl)phenyl)methylsulfonamido)heptanamide;

7-((4-(1H-indol-6-yl)phenyl)(propyl)amino)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-2-(4-methylpiperazin-1-yl)acetamido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-butylureido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(4-methylpentyl)ureido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(3-(dimethylamino)propyl)ureido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-(cyclohexylmethyl)ureido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)pentanamido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)isobutyramido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-2-(4-(2-methoxyethyl)piperazin-1-yl)acetamido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3,3-diethylureido)-N-hydroxyheptanamide;

7-(1-(4-(1H-indol-6-yl)phenyl)-3-ethylureido)-N-hydroxyheptanamide;

N-hydroxy-7-(N-(4-(2-methyl-1H-indol-5-yl)phenyl)methylsulfonamido)heptanamide;

isobutyl 4-(1H-indol-6-yl)phenyl(7-(hydroxyamino)-7-oxoheptyl)carbamate;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)thiophene-2-carboxamide;

N-(7-(hydroxyamino)-7-oxoheptyl)-N-(4-(1-methyl-1H-indazol-6-yl)phenyl)picolinamide;

7-(N-(4-(1H-indol-5-yl)phenyl)methylsulfonamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-1-methylpiperidine-4-carboxamide;

N-(4-(1H-indol-5-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)picolinamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)morpholine-4-carboxamide;

7-(N-(4-(1,2-dimethyl-1H-indol-5-yl)phenyl)methylsulfonamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methylpiperazine-1-carboxamide;

N-hydroxy-7-(N-(4-(1-methyl-1H-indazol-6-yl)phenyl)ethylsulfonamido)heptanamide;

N-(4-(1H-indol-5-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)nicotinamide;

N-(7-(hydroxyamino)-7-oxoheptyl)-4-methyl-N-(4-(1-methyl-1H-indazol-6-yl)phenyl)piperazine-1-carboxamide;

N-(4-(1H-indol-5-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methylpiperazine-1-carboxamide;

7-(N-(4-(1H-indol-5-yl)phenyl)ethylsulfonamido)-N-hydroxyheptanamide;

N-(7-(hydroxyamino)-7-oxoheptyl)-N-(4-(1-methyl-1H-indazol-6-yl)phenyl)morpholine-4-carboxamide;

N-(4-(1H-indol-5-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)morpholine-4-carboxamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-2,6-dimethylmorpholine-4-carboxamide;

N-(7-(hydroxyamino)-7-oxoheptyl)-2,6-dimethyl-N-(4(1-methyl-1H-indazol-6-yl)phenyl)morpholine-4-carboxamide;

N-(4-(1H-indol-5-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-2,6-dimethylmorpholine-4-carboxamide;

N-hydroxy-7-(N-(4-(1-methyl-1H-indol-5-yl)phenyl)methylsulfonamido)heptanamide;

N-hydroxy-7-(N-(4-(1-methyl-1H-indol-6-yl)phenyl)methylsulfonamido)heptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-isopropylpiperazine-1-carboxamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)picolidine-1-carboxamide;

N-(4-(1H-indol-5-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)isonicotinamide;

7-(N-(6-(1H-indol-6-yl)pyridin-3-yl)methylsulfonamido)-N-hydroxyheptanamide;

N-hydroxy-7-(N-(6-(1-methyl-1H-indazol-6-yl)pyridin-3-yl)methylsulfonamido)heptanamide;

7-(N-(6-(1H-indol-5-yl)pyridin-3-yl)methylsulfonamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-4-acetyl-N-(7-(hydroxyamino)-7-oxoheptyl)piperazine-1-carboxamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methyl-1,4-diazepane-1-carboxamide;

N-(7-(hydroxyamino)-7-oxoheptyl)-4-methyl-N-(4-(1-methyl-1H-indol-6-yl)phenyl)piperazine-1-carboxamide;

7-(N-(4-(1H-indol-2-yl)phenyl)methylsulfonamido)-N-hydroxyheptanamide;

tert-butyl 2-(4-(N-(7-(hydroxyamino)-7-oxoheptyl)methylsulfonamido)phenyl)-1H-indole-1-carboxylate;

N-(7-(hydroxyamino)-7-oxoheptyl)-4-methyl-N-(4-(2-methyl-1H-indol-5-yl)phenyl)piperazine-1-carboxamide;

N-(4-(1H-indol-6-yl)phenyl)-4-benzyl-N-(7-(hydroxyamino)-7-oxoheptyl)piperazine-1-carboxamide;

4-ethyl-N-(7-(hydroxyamino)-7-oxoheptyl)-N-(4-(1-methyl-1H-indazole-6-yl)phenyl)piperazine-1-carboxamide;

7-(N-(4-(5-bromo-1H-indol-2-yl)phenyl)methylsulfonamido)-N-hydroxyheptanamide;

tert-butyl 5-bromo-2-(4-(N-(7-(hydroxyamino)-7-oxoheptyl)methylsulfonamido)phenyl)-1H-indazole-1-carboxylate;

N-(4-(1H-indol-6-yl)phenyl)-4-ethyl-N-(7-(hydroxyamino)-7-oxoheptyl)piperazine-1-carboxamide;

N-(4-(1H-indol-5-yl)phenyl)-4-ethyl-N-(7-(hydroxyamino)-7-oxoheptyl)piperazine-1-carboxamide;

N-(7-(hydroxyamino)-7-oxoheptyl)-4-methyl-N-(4-(1-methyl-1H-indol-5-yl)phenyl)piperazine-1-carboxamide;

N-hydroxy-7-(4-methyl-N-(4-(1-methyl-1H-indazol-6-yl)phenyl)piperazine-1-sulfonamide)heptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-(2-methoxyphenyl)piperazine-1-carboxamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-(3-methoxyphenyl)piperazine-1-carboxamide;

N-(4-(3H-benzo[d]imidazol-5-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methylpiperazine-1-carboxamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-(2-hydroxyethyl)piperazine-1-carboxamide;

7-(3-(2-(dimethylamino)ethyl)-1-(4-(1-methyl-1H-indazol-6-yl)phenyl)ureido)-N-hydroxyheptanamide;

N-hydroxy-7-(1-(4-(1-methyl-1H-indazol-6-yl)phenyl)-3-(2-(1-methylpyrrolidin-2-yl)ethyl)ureido)heptanamide;

N-(4-(1H-indol-6-yl)phenyl)-4-butyl-N-(7-(hydroxyamino)-7-oxoheptyl)piperazine-1-carboxamide;

N-(7-(hydroxyamino)-7-oxoheptyl)-4-methyl-N-(4-(1-methyl-1H-indazol-5-yl)phenyl)piperazine-1-carboxamide;

4-ethyl-N-(7-(hydroxyamino)-7-oxoheptyl)-N-(4-(1-methyl-1H-indazol-5-yl)phenyl)piperazine-1-carboxamide;

N-(4-(1H-indol-6-yl)phenyl)-4-(2-(dimethylamino)ethyl)-N-(7-(hydroxyamino)-7-oxoheptyl)piperazine-1-carboxamide;

7-(3-((1-ethylpyrrolidin-2-yl)methyl)-1-(4-(1-methyl-1H-indazol-6-yl)phenyl)ureido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-4-methylpiperazine-1-sulfonamido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-5-yl)phenyl)-4-methylpiperazine-1-sulfonamido)-N-hydroxyheptanamide;

N-(4-(1H-indol-6-yl)phenyl)-N-(7-(hydroxyamino)-7-oxoheptyl)-4-methylpiperazine-1-carboxamide;

7-(N-(4-(1H-indol-6-yl)phenyl)-4-methylpiperazine-1-carbothioamido)-N-hydroxyheptanamide;

7-(N-(4-(1H-indol-5-yl)phenyl)-4-methylpiperazine-1-carbothioamido)-N-hydroxyheptanamide; and

N-hydroxy-7-(4-methyl-N-(4-(1-methyl-1H-indazol-5-yl)phenyl)piperazine-1-carbothioamido)heptaneamide.

7. The hydroxamate compound, isomers thereof, pharmaceutically acceptable salts thereof, or hydrates thereof according to claim 6 , wherein the hydroxamate derivatives are selected from the group consisting of the following compounds:

N-(7-(hydroxyamino)-7-oxoheptyl)-4-methyl-N-(4-(1-methyl-1H-indazol-6-yl)phenyl)piperazine-1-carboxamide;

N-(7-(hydroxyamino)-7-oxoheptyl)-4-methyl-N-(4-(2-methyl-1H-indol-5-yl)phenyl)piperazine-1-carboxamide;

4-ethyl-N-(7-(hydroxyamino)-7-oxoheptyl)-N-(4-(1-methyl-1H-indazol-6-yl)phenyl)piperazine-1-carboxamide; and

N-hydroxy-7-(4-methyl-N-(4-(1-methyl-1H-indazol-6-yl)phenyl)piperazine-1-sulfonamido)heptanamide.

8. Pharmaceutical compositions comprising hydroxamate compound of formula I, isomers thereof, pharmaceutically acceptable salts thereof, or hydrates thereof according to claim 1 together with pharmaceutically acceptable carriers.

9. A method for treating colon cancer, non-small cell lung cancer, or prostate cancer, the method comprising administering pharmaceutical compositions comprising hydroxamate compound of formula I, isomers thereof, pharmaceutically acceptable salts thereof, or hydrates thereof according to claim 1 , together with pharmaceutically acceptable carriers.

10. A method for preparing hydroxamate compounds of the following formula I-2 derivatives, the method comprising the steps of:

allowing a compound of the following formula II to react with bromoaniline in the presence of an inorganic salt so as to prepare a compound of the following formula III;

allowing the compound of formula III to react with 4-nitrophenylchloroformate so as to prepare a compound of the following formula VI;

subjecting the compound of formula VI to the Suzuki reaction with boronic acid in the presence of palladium to prepare a compound of the following formula VII;

allowing the compound of formula VII to react with an amine in the presence of an inorganic salt so as to prepare a compound of the following formula VIII; and

treating the compound of formula VIII with a hydroxide salt, thus preparing a hydroxamate derivative of the following formula I-2:

wherein n is 3, Ar is phenyl, R 1 is 1H-indol-5-yl, 1-methyl-1H-indazol-6-yl, 1-methyl-1H-indazol-5-yl, 3H-benzo[d]imidazol-5-yl, or 1H-indol-6-yl, and R 5 is 1-methylpiperazine, morpholine, 2,6-dimethylmorpholine, 1-ethylpiperazine, N,N-dimethylethane-1,2-diamine, 2-(1-methylpyrrolidin-2-yl)ethanamine, (1-ethylpyrrolidin-2-yl)methanamine, 4-methoxy benzenamine, 3-methoxy benzenamine, 2-methoxy benzenamine, 3,5-dimethoxy benzenamine, thiophen-2-amine, dimethylamine, pyridine-3-amine, methylamine, isopropylamine, isobutylamine, butylamine, 4-methylpentylamine, N,N-dimethylpropane-1,3-diamine, cyclohexylmethylamine, diethylamine, ethylamine, 1-isopropylpiperazine, pyrrolidine, 1-(piperazin-1-yl)ethanone, 1-methylhomopiperazine, 1-benzylpiperazine, 1-(2-methoxyphenyl)piperazine, 1-(3-methoxyphenyl)piperazine, 2-(piperazin-1-yl)ethanol, 1-butylpiperazine, N,N-dimethyl-2-(piperazin-1-yl)ethanamine, or 4-methylpiperidine.

Assignments (4)
CONFIRMATORY PATENT ASSIGNMENT Recorded Sep 17, 2014
From: CHONG KUN DANG HOLDINGS CORP
To: CHONG KUN DANG PHARMACEUTICAL CORP.
Reel/Frame 033762/0975 →
CHANGE OF NAME Recorded Apr 15, 2014
From: CHONG KUN DANG PHARMACEUTICAL CORP.
To: CHONG KUN DANG HOLDINGS CORP.
Reel/Frame 032693/0589 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 22, 2013
From: LEE, SUNG SOOK; LEE, KYUNG JOO; LEE, CHANG SIK; YANG, HYUN MO; KIM, DO HOON; CHOI, DAE KYU; CHOI, HO JIN; KIM, DAL HYUN; HWANG, IN CHANG; KIM, MI JEONG; HAN, BYEONG HOON
To: CHONG KUN DANG PHARMACEUTICAL CORP.
Reel/Frame 030070/0616 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2011
From: LEE, SUNG SOOK; LEE, KYUNG JOO; LEE, CHANG SIK; YANG, HYUN MO; KIM, DO HOON; CHOI, DAE KYU; CHOI, HO JIN; KIM, DAL HYUN; HWANG, IN CHANG; KIM, MI JEONG; HAN, BYEONG HOON
To: CHONG KUN DANG PHARMACEUTICAL CORP.
Reel/Frame 027019/0327 →
Priority Claims (1)
KR 10-2009-0026578 · Mar 27, 2009 · national
Continuity (1)
Related Publication 20120028963A1 · Feb 2, 2012