Chiral arylketones in the treatment of neutrophil-dependent inflammatory diseases
AssigneeDompé Farmaceutici S.P.A.
InventorsMarcello Allegretti, Riccardo Bertini, Maria Candida Cesta, Cinzia Bizzarri, Francesco Colotta
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Abstract
The compounds of formula (I): where Ar is an aromatic ring and Ra, Rb, are as defined in the description, are useful in therapy as drugs for the treatment of diseases mediated by infiltrations of neutrophils induced by IL-8, such as psoriasis, rheumatoid arthritis, ulcerative cholitis and for the treatment of damages caused by ischemia and reperfusion.
Claims8
A method for the treatment of a disease that is selected from the group consisting of psoriasis, rheumatoid arthritis, ulcerative cholitis, acute respiratory distress syndrome (ARDS), glomerulonephritis, and for the prevention and the treatment of damage caused by ischemia and reperfusion, comprising administering to a subject in need thereof an effective amount of a composition comprising (R,S)-1-Arylethylketone compounds of formula I, or their single (R) or (S) enantiomers:
- wherein
- Ar represents phenyl, optionally substituted by one to three substituents, which are the same or different from one another and selected from:
- (C1-C4)alkyl, benzoyl, benzoyloxy, isopropylsulfonyloxy, 2-ethylphenylsulfonylamino, phenoxy, 1-oxo-2-isoindolinyl;
- Ra and Rb are independently chosen from the group consisting of hydrogen;
- linear or branched C1-C6 alkyl;
- phenyl;
- (C1-C4)-alkylphenyl;
- carboxyl;
- carboxy esters of formula CO2R″, wherein R″ is the residue of a linear or branched C1-C6 aliphatic alcohol;
- phosphonates of formula PO(OR″)2 wherein R″ is the residue of a linear or branched C1-C6 aliphatic alcohol;
- 2,3 or 4-pyridyl;
- a group of formula X—(CH2)n—Z, wherein X is a CO, SO or SO2 group, Z is H, phenyl or 2-, 3- or 4-pyridyl and n is zero or an integer from 1 to 3.
A method for treating glomerulonephritis and for treating or preventing damage caused by ischemia and reperfusion, comprising administering to a subject in need thereof an effective amount of a composition comprising (R,S)-1-Arylethylketone compounds of formula I, or their single (R) or (S) enantiomers:
- wherein
- Ar represents phenyl, optionally substituted by one to three substituents, which are the same or different from one another and selected from:
- (C1-C4)alkyl, benzoyl, benzoyloxy, isopropylsulfonyloxy, 2-ethylphenylsulfonylamino, phenoxy, 1-oxo-2-isoindolinyl;
- Ra and Rb are independently chosen from the group consisting of hydrogen;
- linear or branched C1-C6 alkyl;
- phenyl;
- (C1-C4)-alkylphenyl;
- carboxyl;
- carboxy esters of formula CO2R″, wherein R″ is the residue of a linear or branched C1-C6 aliphatic alcohol;
- phosphonates of formula PO(OR″)2 wherein R″ is the residue of a linear or branched C1-C6 aliphatic alcohol;
- 2,3 or 4-pyridyl;
- a group of formula X—(CH2)n—Z, wherein X is a CO, SO or SO2 group, Z is H, phenyl or 2-, 3- or 4-pyridyl and n is zero or an integer from 1 to 3.
Dependencies are inferred from the claim text.