US 7,598,418 B2Granted

Amide derivatives

AssigneeInstitute of Medicinal Molecular Design, Inc.

InventorsSusumu Muto, Akiko Itai

Life of this patent

Estimating the term…

Abstract

A medicament for enhancing an effect of a cancer therapy based on a mode of action of DNA injury, which comprises as an active ingredient a compound represented by the following general formula (I) or a salt thereof: wherein one of R1 and R2 represents hydrogen atom and the other represents the formula —X-A wherein A represents hydrogen atom or an acyl group, X represents oxgen atom or NH; one of R3 and R4 represents hydrogen atom and the other represents the following formula: wherein Y represents a sulfonyl group or a carbonyl group, R5 represents a cyclic group, Z represents a single bond or a C1 to C4 alkylene group, R6 represents hydrogen atom or a C1 to C6 alkyl group.

Claims21

Dependent claims

A composition, which comprises as an active ingredient a substance selected from a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof:

wherein one of R1 and R2 represents hydrogen atom and the other represents the formula —X-A wherein A represents a hydrogen atom, a hydrocarbon-carbonyl group, or a hydrocarbon-sulfonyl group, X represents an oxygen atom or NH;
one of R3 and R4 represents hydrogen atom and the other represents the following formula:
wherein
Y represents a sulfonyl group or a carbonyl group,
R5 represents
a phenyl group which may be substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
a hydroxyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted,
a benzimidazolyl group which may be substituted, or
a cycloalkyl group,
Z represents a single bond or a C1 to C4 alkylene group,
R6 hydrogen atom or a C1 to C6 alkyl group, with the following provisos:
a compound represented by the following formula:
wherein each of A, Z, R5 and R6 has the same meaning as that defined above is excluded;
when one of R1 and R2 is the formula —O—A, A is a hydrogen atom, Y is a carbonyl group, Z is a single bond, and R6 is hydrogen atom, then R5 is
a phenyl group which may be substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted,
a benzimidazolyl group which may be substituted, or
a cycloalkyl group;
when R2 is the formula —NH-A, A is a hydrogen atom, Y is a sulfonyl group, Z is a C1 alkylene group, and R6 is hydrogen atom, then R5 is
a phenyl group which may be substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
a hydroxyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted,
a benzimidazolyl group which may be substituted, or
a cycloalkyl group;
when R1 is the formula —NH-A, A is a hydrogen atom, R3 is a hydrogen atom, Y is a sulfonyl group, Z is a C1 alkylene group, and R6 is hydrogen atom, then R5 is
a phenyl group which may be substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
a hydroxyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted,
a benzimidazolyl group which may be substituted, or
a cycloalkyl group;
and
when one of R1 and R2 is the formula —NH-A, A is a hydrogen atom, Y is a sulfonyl group, Z is a single bond, and R6 is hydrogen atom, then R5 is
a phenyl group which is substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
a hydroxyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted, or
a benzimidazolyl group which may be substituted.

89 more elements

A compound selected from the following compounds or a pharmacologically acceptable salt thereof:

N-Benzyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(2,6-Difluorobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(2,4-Dichlorobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(3-Nitrobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(4-Nitrobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene--1-sulfonamide;
N-(2-Methylbenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-[4-(tert-Butyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-[2-(Trifluoromethyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-[4-(Trifluoromethyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(3,4-Dihydroxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(2-Methoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(3-Methoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(2,3-Dimethoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(3,5-Dimethoxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(3,4-Methylenedioxybenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(3-Aminobenzyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-[4-(Dimethylamino)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-[4-(Methanesulfonyl)benzyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(1-Naphthylmethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-[(5-Methylfuran-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-[(Pyridin-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-[(Benzimidazol-2-yl)methyl]-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-Cyclohexylmethyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-Phenyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(2-Phenethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-(1-Phenethyl)-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-Benzyl-N-methyl-5-{[(4-methylphenyl)sulfonyl]oxy}naphthalene-1-sulfonamide;
N-Benzyl-5-hydroxynaphthalene-1-sulfonamide;
N-(2,6-Difluorobenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(2,4-Dichlorobenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(3-Nitrobenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(4-Nitrobenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(2-Methylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-[4-(tert-Butyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;
N-[2-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;
N-[4-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;
N-(3,4-Dihydroxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(2-Methoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(3-Methoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(2,3-Dimethoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(3,5-Dimethoxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(3,4-Methylenedioxylbenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(3-Aminobenzyl)-5-hydroxynaphthalene-1-sulfonamide;
N-[4-(Dimethylamino)benzyl]-5-hydroxynaphthalene-1-sulfonamide;
N-[4-(Methanesulfonyl)benzyl]-5-hydroxynaphthalene-1-sulfonamide;
N-(1-Naphthylmethyl)-5-hydroxynaphthalene-1-sulfonamide;
N-[(5-Methylfuran-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;
N-[(Pyridin-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;
N-[(Benzimidazol-2-yl)methyl]-5-hydroxynaphthalene-1-sulfonamide;
N-Cyclohexylmethyl-5-hydroxynaphthalene-1-sulfonamide;
N-Phenyl-5-hydroxynaphthalene-1-sulfonamide;
N-(2-Phenethyl)-5-hydroxynaphthalene-1-sulfonamide;
N-(1-Phenethyl)-5-hydroxynaphthalene-1-sulfonamide;
N-Benzyl-N-methyl-5-hydroxynaphthalene-1-sulfonamide;
5-Acetyloxy-N-benzylnaphthalene-2-sulfonamide;
5-Acetyloxy-N-(2,4-dichlorobenzyl)naphthalene-2-sulfonamide;
5-Acetyloxy-N-(3-nitrobenzyl)naphthalene-2-sulfonamide;
5-Acetyloxy-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;
5-Acetyloxy-N-[4-(trifluoromethyl)benzyl]naphthalene-2-sulfonamide;
5-Acetyloxy-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;
5-Acetyloxy-N-(3-aminobenzyl)naphthalene-2-sulfonamide;
5-Acetyloxy-N-(1-naphthylmethyl)naphthalene-2-sulfonamide;
5-Acetyloxy-N-[(5-methylfuran-2-yl)methyl]naphthalene-2-sulfonamide;
5-Acetyloxy-N-[(pyridin-2-yl)methyl]naphthalene-2-sulfonamide;
5-Acetyloxy-N-(cyclohexylmethyl)naphthalene-2-sulfonamide;
5-Acetyloxy-N-phenylnaphthalene-2-sulfonamide;
5-Acetyloxy-N-(2-phenethyl)naphthalene-2-sulfonamide;
5-Acetyloxy-N-(1-phenethyl)naphthalene-2-sulfonamide;
5-Acetyloxy-N-benzyl-N-methylnaphthalene-2-sulfonamide;
N-Benzyl-5-hydroxynaphthalene-2-sulfonamide;
N-(2,4-Dichlorobenzyl)-5-hydroxynaphthalene-2-sulfonamide;
N-(3-Nitrobenzyl)-5-hydroxynaphthalene-2-sulfonamide;
N-[4-(tert-Butyl)benzyl]-5-hydroxynaphthalene-2-sulfonamide;
N-[4-(Trifluoromethyl)benzyl]-5-hydroxynaphthalene-2-sulfonamide;
N-(2,3-Dimethoxybenzyl)-5-hydroxynaphthalene-2-sulfonamide;
N-(3-Aminobenzyl)-5-hydroxynaphthalene-2-sulfonamide;
N-(1-Naphthylmethyl)-5-hydroxynaphthalene-2-sulfonamide;
N-[(5-Methylfuran-2-yl)methyl]-5-hydroxynaphthalene-2-sulfonamide;
N-[(Pyridin-2-yl)methyl]-5-hydroxynaphthalene-2-sulfonamide;
N-(Cyclohexylmethyl)-5-hydroxynaphthalene-2-sulfonamide;
N-Phenyl-5-hydroxynaphthalene-2-sulfonamide;
N-(2-Phenethyl)-5-hydroxynaphthalene-2-sulfonamide;
N-(1-Phenethyl)-5-hydroxynaphthalene-2-sulfonamide;
N-Benzyl-N-methyl-5-hydroxynaphthalene-2-sulfonamide;
5-Acetylamino-N-benzylnaphthalene-2-sulfonamide;
5-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;
5-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;
5-Acetylamino-N-benzyl-N-methylnaphthalene-2-sulfonamide;
5-Amino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;
5-Amino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;
5-Amino-N-benzyl-N-methylnaphthalene-2-sulfonamide;
6-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-1-sulfonamide;
6-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-1-sulfonamide;
6-Amino-N-[4-(tert-butyl)benzyl]naphthalene-1-sulfonamide;
6-Amino-N-(2,3-dimethoxybenzyl)naphthalene-1-sulfonamide;
6-Acetylamino-N-benzylnaphthalene-2-sulfonamide;
6-Acetylamino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;
6-Acetylamino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;
6-Amino-N-[4-(tert-butyl)benzyl]naphthalene-2-sulfonamide;
6-Amino-N-(2,3-dimethoxybenzyl)naphthalene-2-sulfonamide;
5-Amino-N-benzylnaphthalene-1-carboxamide;
5-Amino-N-[4-(tert-butyl)benzyl]naphthalene-1-carboxamide;
and
5-Amino-N-(2,3-dimethoxybenzyl)naphthalene-1-carboxamide.

101 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/510,242Filed 18 Apr 2003
Priority: JP 2002-11562918 Apr 2002
Published: US 2005/0215645 A129 Sep 2005
Granted: 6 Oct 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 213/42
Radicals substituted by singly-bound nitrogen atoms: having hetero atoms attached to the substituent nitrogen atom
A61K 31/166
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g.…
A61K 31/167
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the nitrogen of a carboxamide group directly attached to the aromatic ring,…
A61K 31/18
Amides, e.g. hydroxamic acids: sulfonamides

Family

US 2005/0215645 A1Pre-grant publication · published 29 Sep 2005
US 7,598,418 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A composition, which comprises as an active ingredient a substance selected from a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof:

wherein one of R1 and R2 represents hydrogen atom and the other represents the formula —X-A wherein A represents a hydrogen atom, a hydrocarbon-carbonyl group, or a hydrocarbon-sulfonyl group, X represents an oxygen atom or NH;
one of R3 and R4 represents hydrogen atom and the other represents the following formula:
wherein
Y represents a sulfonyl group or a carbonyl group,
R5 represents
a phenyl group which may be substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
a hydroxyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted,
a benzimidazolyl group which may be substituted, or
a cycloalkyl group,
Z represents a single bond or a C1 to C4 alkylene group,
R6 hydrogen atom or a C1 to C6 alkyl group, with the following provisos:
a compound represented by the following formula:
wherein each of A, Z, R5 and R6 has the same meaning as that defined above is excluded;
when one of R1 and R2 is the formula —O—A, A is a hydrogen atom, Y is a carbonyl group, Z is a single bond, and R6 is hydrogen atom, then R5 is
a phenyl group which may be substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted,
a benzimidazolyl group which may be substituted, or
a cycloalkyl group;
when R2 is the formula —NH-A, A is a hydrogen atom, Y is a sulfonyl group, Z is a C1 alkylene group, and R6 is hydrogen atom, then R5 is
a phenyl group which may be substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
a hydroxyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted,
a benzimidazolyl group which may be substituted, or
a cycloalkyl group;
when R1 is the formula —NH-A, A is a hydrogen atom, R3 is a hydrogen atom, Y is a sulfonyl group, Z is a C1 alkylene group, and R6 is hydrogen atom, then R5 is
a phenyl group which may be substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
a hydroxyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted,
a benzimidazolyl group which may be substituted, or
a cycloalkyl group;
and
when one of R1 and R2 is the formula —NH-A, A is a hydrogen atom, Y is a sulfonyl group, Z is a single bond, and R6 is hydrogen atom, then R5 is
a phenyl group which is substituted with one or more substituents selected from
a halogen atom,
a nitro group,
an alkyl group,
a halogenated alkyl group,
a hydroxyl group,
an alkoxy group,
an alkylenedioxy group,
an amino group,
an N,N-di(alkyl)-amino group, and
an alkyl-sulfonyl group,
a naphthyl group which may be substituted,
a furyl group which may be substituted,
a pyridyl group which may be substituted, or
a benzimidazolyl group which may be substituted.

89 more elements

Facts

Application

10/510,242Filed 18 Apr 2003

Priority

JP 2002-11562918 Apr 2002

Published

US 2005/0215645 A129 Sep 2005

Granted

6 Oct 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

C07D 213/42
Radicals substituted by singly-bound nitrogen atoms: having hetero atoms attached to the substituent nitrogen atom
A61K 31/166
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g.…
A61K 31/167
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the nitrogen of a carboxamide group directly attached to the aromatic ring,…
A61K 31/18
Amides, e.g. hydroxamic acids: sulfonamides