| abstract |
A compound of formula (1) or a salt or solvate acceptable for pharmaceutical use thereof, in which: R 1 is selected from the group consisting of H, alkyl, C 1-6 haloalkyl, cycloalkyl, cycloalkyl N-, arylalkyl, heterocycloalkyl, heteroaryl, -N (R2) 2, -N (R2) 2aryl, unsubstituted aryl and aryl substituted with one to three X, where each R2 may be the same or different and is independently selected when more than one R2 is present; R2 is selected from the group consisting of H and C1-6 alkyl; R3 is 1-3 substituents selected from the group consisting of H, C1-6 alkyl, Cl, F, CF3, OCF2H, OCF3, OH and C1-6 alkoxy, wherein R3 can be the same or different and is independently selected when there is more of an R3 present; R4 is selected from the group consisting of H, C1-6 alkyl, alkenyl cycloalkyl, aryl, benzyl, heteroaryl, heterocycloalkyl, arylNH-, heteroarylNH-, cycloalkylNH-, -N (R2) 2 or -N (R2) aryl, said alkyl , alkoxy, cycloalkyl, alkenyl, phenyl, pyridine-N-oxide and heteroaryl optionally substituted with one to three X, wherein X may be the same or different and is independently selected when more than one X is present; R5 is H or C1-6 alkyl; R6 is H or C1-6 alkyl; or R5 and R6 taken together with the carbon atom to which they are attached form a carbonyl group; L1 is of formula (2), - C (R2) 2-, -C (O) -, -CHOR2-, -C = NOR5-, -SO2-, -SO-, -S-, -O-, - N (R2) -, -C (O) NR2-, -N (R2) C (O) -, -CHCF2- or -CF2-; L2 is a covalent bond, C1-6 alkylene, -C (R2) 2-, a formula (3), -CHOR2-, -C (R2) OH, -C = NOR5-, -SO2-, -N (R2 ) SO2-, -SO-, -S-, -O-, -SO2N (R2) -, -N (R2) 2-, -C (O) N (R2) - or -N (R2) C (O ) -; X is selected from the group consisting of H, halogen, CF3, CN, OCF2H, OCF2CF3, OCF3, OR2, C1-6 alkyl, cycloalkyl, cycloalkoxy, C1-6 alkoxy, (C1-6) alkoxy, -O-cycloalkyl, cycloalkylamino, cycloalkylalkoxy, heteroalkyl, -OSO2R2, -COOR2, -CON (R2) 2, N (R2) 2 and NR2alkyl, wherein X may be the same or different, and is independently selected when more than one X is present; Y is a covalent bond, -CH2-, -SO2- or -C (O) -; Z is a covalent bond, -CH2-, -SO2- or -C (O) -; or Y, R1, Z and R2 can be taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl; with the following caveats: L2 and R4, when taken together, cannot have two heteroatoms covalently bonded together; when R2 is H, Z cannot be -S (O) -, -SO2- or -C (O) -; and when Y is a covalent bond, R1 cannot form an N-N bond with the nitrogen atom. A prodrug thereof, or a salt, solvate or stereoisomers of the compound or said prodrug, which exhibit anti-inflammatory and immunomodulatory activity. Pharmaceutical compositions containing such compounds, a process for their preparation and the use of the compounds, alone or in combination, for the preparation of medicaments for the treatment of cutaneous T-cell lymphoma, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis are also presented. , glaucoma, diabetes, sepsis, shock, sarcoidosis, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia, retinal disease, scleroderma, osteoporosis, renal ischemia, myocardial infarction, stroke, cerebral ischemia, nephritis, hepatitis, glomerulonephritis, cryptogenic fibrosing alveolitis, psoriasis atopic dermatitis, vasculitis, allergy, seasonal allergic rhinitis, Crohn's disease, inflammatory bowel disease, reversible airway obstruction, adult respiratory failure syndrome, chronic lung disease (COPD), bronchitis, colitis, coronary heart disease, melanoma, rejection of transplant s, graft versus host disease, Hashimoto's thyroiditis, Graves' disease, myasthenia gravis or Goodpasture's syndrome, to a patient in need of such treatment. |