2-aryl-acetic acids, their derivatives and pharmaceutical compositions containing them

1. A method of treatment of psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of ischemia-reperfusion injury comprising administering a compound of formula (I):

or a pharmaceutically acceptable salt thereof,

wherein

A is selected from the group consisting of benzene, pyrrole, and indole;

labels 1 and 2 mark the relevant positions on the A ring;

the X atom is nitrogen or carbon;

R is a substituting group on the A ring selected from:

a group in the 3 (meta) position that is linear or branched C 1 -C 5 alkyl, linear or branched C 2 -C 5 -alkenyl, linear or branched C 2 -C 5 -alkynyl, substituted or not-substituted phenyl, linear or branched C 1 -C 5 hydroxyalkyl, C 2 -C 5 -acyl, substituted or not-substituted benzoyl;

a group in the 4 (para) position that is C 1 -C 5 -alkyl, C 2 -C 5 -alkenyl, C 2 -C 5 -alkynyl group, C 3 -C 6 -cycloalkyl, C 1 -C 5 -acyloxy, substituted or not substituted benzoyloxy, C 1 -C 5 -acylamino, substituted or not-substituted benzoylamino, C 1 -C 5 -sulfonyloxy, substituted or not-substituted benzenesulfonyloxy, C 1 -C 5 -alkanesulfonylamino, substituted or not-substituted benzenesulfonylamino, C 1 -C 5 -alkanesulfonylmethyl, substituted or not-substituted benzenesulfonylmethyl, 2-furyl; 3-tetrahydrofuryl; 2-thiophenyl; 2-tetrahydrothiophenyl, C 1 -C 8 -alkanoyl, cycloalkanoyl or arylalkanoyl-C 1 -C 5 -alkylamino;

Hy is selected from the group consisting of methyl, ethyl, chlorine, bromine, methoxy, trifluoromethyl;

Y is NH; and

R′ is selected from

H, C 1 -C 5 -alkyl, C 3 -C 5 -cycloalkyl, C 2 -C 5 -alkenyl;

an amino acid residue consisting of straight or branched C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 6 -alkenyl, phenylalkyl substituted with one or more carboxy (COOH) groups;

an amino acid residue consisting of straight or branched C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 6 -alkenyl, phenylalkyl, bearing along the chain a heteroatom selected from oxygen and sulfur and with one or more carboxy (COOH) groups;

a residue of formula —CH 2 —CH 2 —Z—(CH 2 —CH 2 O)nR″ wherein R″ is H or C 1 -C 5 -alkyl, n is an integer from 0 to 2 and Z is oxygen or sulfur;

a residue of formula —(CH 2 )n-NRaRb wherein n is an integer from 0 to 5 and each Ra and Rb, which may be the same or different, are C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or, alternatively, Ra and Rb, together with the nitrogen atom to which they are bound, form a heterocycle from 3 to 7 members of formula (II)

wherein W represents a single bond, CH 2 , 0, S or N-Rc, wherein Rc is H, C 1 -C 6 -alkyl or C 1 -C 6 -alkylphenyl;

a residue OR″ wherein R″ is H, methyl or carboxymethyl.

2. The method of claim 1 , wherein R′ is:

the amino acid residue of glycine, β-alanine, γ-aminobutyric acid or residues of an L-α-amino acid selected in the group of L-alanine, valine, leucine, isoleucine, nor-leucine, phenylalanine, S-methylcysteine, methionine;

a residue of formula —CH 2 —CH 2 —O—(CH 2 —CH 2 O)R″ wherein R″ is H or C 1 -C 5 -alkyl;

a residue of formula —(CH 2 )n-NRaRb wherein n is an integer from 2 to three, more preferably 3, and the group NRaRb is N,N-dimethylamine, N,N-diethylamine, 1-piperidyl, 4-morpholyl, 1-pyrrolidyl, 1-piperazinyl, 1-(4-methyl)piperazinyl;

a residue OR″ wherein R″ is H or methyl.

3. The method of claim 1 , wherein R is 3′-benzoyl, 3′-(4-chloro-benzoyl), 3′-(4-methyl-benzoyl), 3′-acetyl, 3′-propionyl, 3′-isobutanoyl, 3′-ethyl, 3′-isopropyl, 4′-isobutyl, 4′-trifluoromethanesulphonyloxy, 4′-benzenesulphonyloxy, 4′-trifluoromethanesulphonylamino, 4′-benzenesulphonylamino, 4′-benzenesulphonylmethyl, 4′-acetyloxy, 4′-propionyloxy, 4′-benzoyloxy, 4′-acetylamino, 4′-propionylamino, 4′-benzoylamino.

4. The method of claim 1 , wherein the compound of formula (I) is selected from:

(5-acetyl-1-methyl-1-pyrrol-2-yl)acetamide;

(5-acetyl-1-methyl-1H-pyrrol-2-yl)-N-carboxymethylacetamide;

(S)(5-acetyl-1-methyl-1H-pyrrol-2-yl)-N-(2-carboxyethyl)acetamide;

(5-acetyl-1-methyl-1-H-pyrrol-2-yl)-N-(3-dimethylaminopropyl)acetamide;

(S)(5-acetyl-1-methyl-1H-pyrrol-2-yl)-N-(1-carboxy-2-methoxyethyl)acetamide;

(4-isobutyl-2-methylphenyl)acetamide;

(2-chloro-3-propionylphenyl)-N-(3-dimethylaminoethyl)acetamide;

(3-isopropyl-2-methylphenyl)-N-[3-(1-piperidinyl)propyl]acetamide;

(3-benzoyl-2-methylphenyl)acetamide;

(1-benzoyl-2-methyl-1H-indol-3-yl)acetamide;

(1-benzoyl-2-methyl-1H-indol-3-yl)-N-(3-dimethylaminopropyl)acetamide;

[1-(4-chlorobenzoyl)-2-methyl-1H-indol-3-yl]acetamide;

[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide;

{2-chloro-4-[(trifluoromethanesulphonyl)oxy]phenyl}-N-(2-hydroxyethoxyethyl)acetamide;

(1-benzoyl-2-methyl-1H-pyrrol-3-yl)-N-(2-methoxyethyl)acetamide;

(1-benzoyl-2-chloro-1H-pyrrol-3-yl)-N-[3-(1-morpholino) propyl]acetamide;

(5-isobutyryl-1-methyl-1H-pyrrol-2-yl)acetamide;

(5-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-(2-carboxymethyl)acetamide;

[1-methyl-5-(4-chlorobenzoyl)-1H-pyrrol-2-yl]-N-(2-hydroxyethoxyethyl)acetamide;

[1-methyl-5-(4-chlorobenzoyl)-1H-pyrrol-2-yl]acetamide;

{2-methyl-4-[(phenylsulphonyl)amino]phenyl}-N-(3-dimethylaminopropyl)acetamide; and

(3-benzoyl-2-methoxyphenyl)acetamide.