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

Use of 2-arylacetic acid compounds and derivatives of formula (I):

• and pharmaceutically acceptable salts thereof,
• wherein
• A includes the X atom and represents a 5-6 membered aromatic or heteroaromatic ring optionally including a heteroatom, or a further heteroatom when X is N, selected from N (nitrogen), O (oxygen), S (sulfur);
• the 5-6 membered aromatic or heteroaromatic ring is optionally fused with a second ring to give bicyclic aromatic or heteroaromatic structures;
• labels 1 and 2 mark the relevant positions on the A ring;
• the X atom is selected from N (nitrogen) and C (carbon);
• R is a substituting group on the A ring selected from:
• a group in the 3 (meta) position selected from a linear or branched C1-C5 alkyl, C2 C5-alkenyl or C2-C5-alkynyl group, substituted or not-substituted phenyl, linear or branched C1-C5 hydroxyalkyl, C2-C5-acyl, substituted or not-substituted benzoyl;
• a group in the 4 (para) position selected from C1-C5 alkyl, C2-C5-alkenyl or C2-C5-alkynyl group, C3-C6-cycloalkyl, C1-C5-acyloxy, substituted or not-substituted benzoyloxy, C1-C5-acylamino, substituted or not-substituted benzoylamino, C1-C5-sulfonyloxy, substituted or not-substituted benzenesulfonyloxy, C1-C5-alkanesulfonylamino, substituted or not-substituted benzenesulfonylamino, C1-C5-alkanesulfonylmethyl, substituted or not-substituted benzenesulfonylmethyl, 2-furyl;
• 3-tetrahydrofuryl;
• 2 thiophenyl;
• 2-tetrahydrothiophenyl groups or a C1-C8-alkanoyl, cycloalkanoyl or arylalkanoyl-C1-C5-alkylamino group;
• Hy is a small hydrophobic group with a steric hindrance factor ν ranging between 0.5 and 0.9 Å (where ν is the Charton steric constant for substituents), including methyl, ethyl, chlorine, bromine, methoxy, trifluoromethyl;
• the Y group is selected from 0 (oxygen) and NH;
• when Y is 0 (oxygen), R′ is H (hydrogen);
• when Y is NH, R′ is selected from
• —H, C1-C5-alkyl, C1-C5-cycloalkyl, C1-C5-alkenyl;
• an amino acid residue consisting of straight or branched C1-C6-alkyl, C1-C6-cycloalkyl, C1-C6-alkenyl, phenylalkyl substituted with one or more carboxy (COOH) groups;
• an amino acid residue consisting of straight or branched C1-C6-alkyl, C1-C6-cycloalkyl, C1-C6-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 —CH2—CH2-Z-(CH2—CH2O)nR″ wherein R″ is H or C1-C5-alkyl, n is an integer from 0 to 2 and Z is oxygen or sulfur;
• a residue of formula —(CH2)n—NRaRb wherein n is an integer from 0 to 5 and each Ra and Rb, which may be the same or different, are C1-C6-alkyl, C1-C6-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, CH2, O, S or N-Rc, wherein Rc is H, C1-C6-alkyl or C1-C6-alkylphenyl;
• a residue OR″ wherein R″ is H, methyl, carboxymethyl;
• a residue of formula SO2Rd wherein Rd is C1-C6-alkyl, C1-C6-cycloalkyl, C1-C6-alkenyl;
• in the preparation of a medicament for the treatment of diseases that involve IL-8 induced human PMNs chemotaxis, such as psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and in the prevention and treatment of damages caused by ischemia and reperfusion.