| 摘要 |
Disclosed is the use of a quinoline compound of formula [1] or a pharmaceutically acceptable salt, N-oxide, hydrate or solvate thereof, R1 R2, R3, R4 and R5 are independently hydrogen, alkyl, fully or partially fluorinated alkyl, cyclopropyl, halo, -S(O)nR6, -SO2NR7R8, -NR7R8, -NR7C(O)R5, -CO2R7, -C(O)NR7R8, -C(O)R6, -nitro, -CN or a group -OR9 wherein each R6 is independently alkyl, fully or partially fluorinated alkyl, cycloalkyl, aryl, or heteroaryl. R7, R8 are independently alkyl, fully or partially fluorinated alkyl, cycloalkyl, cycloalkyl-alkyl-, aryl, heteroaryl or hydrogen, R9 is alkyl, fully or partially fluorinated alkyl, cycloalkyl, cylcoalkyl-(alkyl)-, or a group -SO2R6. A is -CHR10-, -C(O)-, -S(O)n-, -O-, or -NR10- wherein n is an integer from 0-2 and R10 is hydrogen, alkyl, or fully or partially fluorinated alkyl group. B is a divalent radical selected from -CH2-, -CH2CH2-, -CHR11-, -C11R12-, -CH2CHR11-, CH2CR11R12-, -CHR11CHR12- in either orientation, -CH20- or -OCH(CH3)O- wherein the oxygen is attached to the ring carrying R1, R2 and R3 and -(CR11R12)p-Z- wherein Z is attached to the ring carrying R1, R2 and R3 wherein R11 is alkyl, cyclopropyl, or fully or partially fluorinated alkyl, R12 is methyl or fully or partially fluorinated methyl, p is independently 1 or 2 and Z is -O-, -NH-, or -S(O)n-, wherein n is an integer from 0-2. X is a carboxylic acid, tetrazole, 3-hydroxyisoxazole, hydroxamic acid, phosphinate, phosphonate, phosphonamide, or sulfonic acid group, or a group of formula C(=O)NHSO2R6 or SO2NHC(=O)R6 and Y is aryl, heteroaryl, aryl-fused-heterocycloalkyl, heteroaryl-fused-cycloalkyl, heteroaryl-fused-heterocycloalkyl or aryl-fused-cycloalkyl group for the manufacture of a medicament for use in the treatment of a condition selected from asthma, chronic obstructive pulmonary disease, allergic airway syndrome, bronchitis, cystic fibrosis, emphysema, rhinitis, psoriasis, atopic and non-atopic dermatitis, Crohn's disease, ulcerative colitis, and irritable bowel disease. Also disclosed are a selection of the said compounds and pharmaceutical compositions comprising said compounds.
|
