US 2008/0076807 A1Published application

Alpha-Amino Acid Derivatives with Antiinflammatory Activity

AssigneeItalfarmaco S.p.A.

InventorsMassimo Pinori, Rocco Mazzaferro, Paolo Mascagni

Life of this patent

Estimating the term…

Abstract

Compounds of the formula: are described in which Z, Q, X, L, m and n assume the meanings stated in the description. The compounds (I) inhibit the production of TNF α and may thus be useful in the treatment of inflammation and pathological conditions involving overproduction of said cytokine. They furthermore exhibit significant inhibitory activity on the proliferation of tumour cells and may thus be used for the treatment and/or prevention of tumorous, neurodegenerative or autoimmune disorders.

Claims14

Dependent claims

A compound of the formula (I)

in which
Z is linear or branched C1-C4 alkyl, aryl, arylalkyl or a saturated, unsaturated or partially unsaturated mono-, di- or tricyclic carbocyclic residue, or a saturated, unsaturated or partially unsaturated mono-, di- or tricyclic heterocyclic residue comprising one or more heteroatoms selected from among N, S or O, said C1-C4 alkyl, aryl, arylalkyl, carbocyclic or heterocyclic residue optionally being substituted with one or more mutually identical or different residues, selected from among:
halogen, lower alkyl, lower alkoxyl, lower haloalkyl, alkylsulfonyl, cycloalkyl, (cycloalkyl)alkyl, alkanoyl, amino optionally mono- or disubstituted with C1-C4 alkyl, (C1-C4) aminoalkyl, optionally mono- or disubstituted with C1-C4 alkyl, carboxy, C1-C4 alkoxycarbonyl, mercaptoalkoxy, mercaptophenoxy, nitro, cyano, oxo, perfluoroalkoxy, perfluoroalkyl, phenyl, phenoxy, phenylalkoxy, benzoyloxy, phenylalkyl, benzoyl, phenylsulfonyl and hydroxy;
Q is aryl, arylalkyl or a saturated, unsaturated or partially unsaturated mono-, di- or tricyclic carbocyclic residue, or a saturated, unsaturated or partially unsaturated mono-, di- or tricyclic heterocyclic residue comprising one or more heteroatoms selected from among N, S or O;
said aryl, arylalkyl, carbocyclic or heterocyclic residue optionally being substituted with one or more mutually identical or different residues, selected from among:
halogen, lower alkyl, lower alkoxyl, lower haloalkyl, alkylsulfonyl, cycloalkyl, (cycloalkyl)alkyl, alkanoyl, amino optionally mono- or disubstituted with C1-C4 alkyl, (C1-C4) aminoalkyl, optionally mono- or disubstituted with C1-C4 alkyl, carboxy, C1-C4 alkoxycarbonyl, mercaptoalkoxy, mercaptophenoxy, nitro, cyano, oxo, perfluoroalkoxy, perfluoroalkyl, phenyl, phenoxy, phenylalkoxy, benzoyloxy, phenylalkyl, benzoyl, phenylsulfonyl and hydroxy;
m and n are independently 0 or 1;
X is C1-C4 alkylene or is absent;
L is phenylene, cyclohexylene or a linear or branched alkyl chain with 2 to 6 carbon atoms, optionally containing one or more double bonds;
and the pharmaceutically acceptable salts thereof.

7 more elements

A compound selected from among:

4-(2(R)-Benzoylamino-3-naphthalen-2-yl-propionylamino)-N-hydroxy-benzamide
4-(2(R)-Acetylamino-3-naphthalen-2-yl-propionylamino)-N-hydroxy-benzamide
4-(2(S)-Acetylamino-2-indan-2-yl-acetylamino)-N-hydroxy-benzamide
4-(2(S)-Acetylamino-3-naphthalen-2-yl-propionylamino)-N-hydroxy-benzamide
4-(2(S)-Acetylamino-3-phenyl-propionylamino)-N-hydroxy-benzamide
4-(2(S)-Benzoylamino-3-biphenyl-4-yl-propionylamino)-N-hydroxy-benzamide
4-(2(S)-Benzoylamino-3-naphthalen-2-yl-propionylamino)-N-hydroxy-benzamide
4-(2(S)-Benzoylamino-3-phenyl-propionylamino)-N-hydroxy-benzamide
4-[2(S)-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-N-hydroxy-benzamide
4-[2(S)-Acetylamino-3-(4-trifluoromethyl-phenyl)-propionylamino]-N-hydroxy-benzamide
4-[2(S)-Benzoylamino-3-(4-hydroxy-phenyl)-propionylamino]-N-hydroxy-benzamide
4-Amino-N-[1(R)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-naphthalen-2-yl-ethyl]-benzamide
4-Amino-N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-naphthalen-2-yl-ethyl]-benzamide
5-Bromo-N-[1(R)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-naphthalen-2-yl-ethyl]-nicotinamide
5-Bromo-N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-(4-trifluoromethyl-phenyl)-ethyl]-nicotinamide
5-Bromo-N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-biphenyl-4-yl-ethyl]-nicotinamide
5-Bromo-N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-naphthalen-2-yl-ethyl]-nicotinamide
N-[1(R)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-naphthalen-2-yl-ethyl)-amide of benzo[1,3]dioxole-5-carboxylic acid
N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-(4-hydroxy-phenyl)-ethyl]-amide of benzo[1,3]dioxole-5-carboxylic acid
N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-naphthalen-2-yl-ethyl]-amide of benzo[1,3]dioxole-5-carboxylic acid
N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-(3-fluoro-phenyl)-ethyl]-amide of benzo[1,3]dioxole-5-carboxylic acid
N-[1(R)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-naphthalen-2-yl-ethyl]-amide of naphthalene-2-carboxylic acid
N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-(4-trifluoromethyl-phenyl)-ethyl]-amide of naphthalene-2-carboxylic acid
N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-phenyl-ethyl]-amide of naphthalene-2-carboxylic acid
N-[1(S)-(4-hydroxycarbamoyl-phenylcarbamoyl)-2-(biphenyl-4-yl)-ethyl]-amide of naphthalene-2-carboxylic acid.

22 more elements

Dependencies are inferred from the claim text.

patentgrep

Loading patent…

Abstract

A compound of the formula (I)

in which
Z is linear or branched C1-C4 alkyl, aryl, arylalkyl or a saturated, unsaturated or partially unsaturated mono-, di- or tricyclic carbocyclic residue, or a saturated, unsaturated or partially unsaturated mono-, di- or tricyclic heterocyclic residue comprising one or more heteroatoms selected from among N, S or O, said C1-C4 alkyl, aryl, arylalkyl, carbocyclic or heterocyclic residue optionally being substituted with one or more mutually identical or different residues, selected from among:
halogen, lower alkyl, lower alkoxyl, lower haloalkyl, alkylsulfonyl, cycloalkyl, (cycloalkyl)alkyl, alkanoyl, amino optionally mono- or disubstituted with C1-C4 alkyl, (C1-C4) aminoalkyl, optionally mono- or disubstituted with C1-C4 alkyl, carboxy, C1-C4 alkoxycarbonyl, mercaptoalkoxy, mercaptophenoxy, nitro, cyano, oxo, perfluoroalkoxy, perfluoroalkyl, phenyl, phenoxy, phenylalkoxy, benzoyloxy, phenylalkyl, benzoyl, phenylsulfonyl and hydroxy;
Q is aryl, arylalkyl or a saturated, unsaturated or partially unsaturated mono-, di- or tricyclic carbocyclic residue, or a saturated, unsaturated or partially unsaturated mono-, di- or tricyclic heterocyclic residue comprising one or more heteroatoms selected from among N, S or O;
said aryl, arylalkyl, carbocyclic or heterocyclic residue optionally being substituted with one or more mutually identical or different residues, selected from among:
halogen, lower alkyl, lower alkoxyl, lower haloalkyl, alkylsulfonyl, cycloalkyl, (cycloalkyl)alkyl, alkanoyl, amino optionally mono- or disubstituted with C1-C4 alkyl, (C1-C4) aminoalkyl, optionally mono- or disubstituted with C1-C4 alkyl, carboxy, C1-C4 alkoxycarbonyl, mercaptoalkoxy, mercaptophenoxy, nitro, cyano, oxo, perfluoroalkoxy, perfluoroalkyl, phenyl, phenoxy, phenylalkoxy, benzoyloxy, phenylalkyl, benzoyl, phenylsulfonyl and hydroxy;
m and n are independently 0 or 1;
X is C1-C4 alkylene or is absent;
L is phenylene, cyclohexylene or a linear or branched alkyl chain with 2 to 6 carbon atoms, optionally containing one or more double bonds;
and the pharmaceutically acceptable salts thereof.

7 more elements