| 摘要 |
The invention relates to new substituted naphthyridines of formula 1, as well as pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof,;
wherein
R1 is selected from among —O—R3 or —NR3R4,R3 is C1-6-alkyl which is substituted by R5 and R6,R5 is selected from hydrogen, branched or linear C1-6-alkyl, C2-6-alkenyl, —C1-6-alkylen-O—C1-3-alkyl, C1-3-haloalkyl,
R6 is ring X;
wherein n is either 0 or 1,
and is a either a single or a double bond andwherein A, B, D and E are each independently from one another selected from CH2, CH, C, N, NH, O or S and wherein ring X is attached to the molecule either via position A, B, D or E, wherein said ring X may optionally be further substituted by one, two or three residues each selected individually from the group consisting of -oxo, hydroxy, —C1-3-alkyl, —C1-3-haloalkyl, —O—C1-3-alkyl, —C1-3-alkanol and halogen,and wherein R4, R2, R7, R8, R9, R10, R11 and Q may have the meanings as given in claim 1, as well as pharmaceutical compositions containing these compounds. |
| 主权项 |
1. A method of treating a disease comprising administering a therapeutically effective amount of a compound of formula 1, to a patient in need thereof, wherein:R1 is selected from among —O—R3 or —NR3R4 wherein R3 is C1-6-alkyl which is substituted by R5 and R6 wherein R5 is selected from hydrogen, branched or linear C1-6-alkyl, C2-6-alkenyl, —C1-6-alkylen-O—C1-3-alkyl, C1-3-haloalkyl, wherein R6 is ring X wherein n is either 0 or 1, wherein is a either a single or a double bond and wherein A, B, D and E are each independently from one another selected from CH2, CH, C, N, NH, O or S and wherein ring X is attached to the molecule either via position A, B, D or E, wherein said ring X may optionally be further substituted by one, two or three residues each selected individually from the group consisting of -oxo, hydroxy, —C1-3-alkyl, —C1-3-haloalkyl, —O—C1-3-alkyl, —C1-3-alkanol and halogen, R4 is selected from the group consisting of hydrogen and C1-6-Alkyl, R2 is selected from the group consisting of hydrogen; 5- to 10-membered aryl; 5- to 10-membered heteroaryl comprising 1, 2 or 3 heteroatoms each individually selected from among N, O and S; 5- to 10-membered, saturated or partially unsaturated heterocyclus comprising 1, 2 or 3 heteroatoms each individually selected from among N, O and S; 3- to 10-membered saturated or partially unsaturated cycloalkyl, wherein—in case that R2 is not hydrogen—said R2 may optionally be substituted by 1, 2, 3 or 4 residues each individually selected from the group consisting of hydrogen, -oxo, halogen, —C1-6-alkyl, —C2-6-alkenyl, —C1-6-alkylene-COOH, —COOH, —CO—NR9R10, —C1-6-alkylene-CO—NR9R10, —C1-6-alkylene-NR9R10, —C1-6-alkylene-CO-Q, —CO-Q, —C1-6-alkylene-CO—NR9Q, —CO—NR9Q, —C1-6-alkylene-NR11—CO—NR9R10, —C1-6-alkylene-NR11—CO-Q, —C1-6-alkylene-NR11—SO2R9, —C1-6-alkylene-O—CO—R9, —C1-6-alkylene-O—CO—NR9R10, —C1-6-alkylene-O—R9, —C1-6-alkylene-SO—NR9R10, —C1-6-alkylene-SO2R9, —C1-6-alkylene-SOR9, —C1-6-alkinylene-O—R9, —C1-6-alkinylene-O, —C1-6-alkinylene-NR9R10, C5-10-aryl, -Q, —C3-8-cycloalkyl, —O—R7, —O—C1-6-alkylene-R7, —O—C1-6-alkylene-O—R7, —C1-3-haloalkyl, cyanide, —NR11R7, —NR11(C1-6-alkylene-R7), —S(O)—C1-6-alkyl, —SO2—C1-6-alkyl, —S—C1-6-alkyl, —SO2—NR9R10, —SO2—NR11Q, 5- to 10-membered heteroaryl comprising 1, 2 or 3 heteroatoms each individually selected from among N, O and S, —NR11—CO—R7 and —O—CO—R7, wherein R7 is selected from the group consisting of hydrogen; branched or linear —C1-6-alkyl; —C1-6-haloalkyl; —C1-6-alkylene-COOH; —C1-6-alkylen-CO—NR9R10; —C1-6-alkylene-CO-Q; —C2-6-alkylene-NR11—CO—NR9R10; —C2-6-alkylene-NR11—CO-Q; —C2-6-alkylene-NR11—SO2R9; —C2-6-alkylene-NR9R10; —C2-6-alkylene-Q; —C2-6-alkylene-O—CO—R9, —C2-6-alkylene-O—CO—NR9R10, —C2-6-alkylene-SO—NR9R10, —C2-6-alkylene-SO2—R9, —C2-6-alkylene-SO—R9, —SO2—R9, —SO—R9, —SO2—NR9R10, —SO2—NR11Q, —SO2-Q, —C1-6-alkylene-O—R9; —CO—NR9R10, —CO—NR9Q, —CO—R9, —CO-Q, —C1-6-alkylene-Q, —C5-10-aryl, -Q, 3- to 8-membered saturated or partially unsaturated cycloalkyl; 5- to 10-membered heteroaryl comprising 1, 2 or 3 heteroatoms each individually selected from among N, O and S; —C1-6-alkylene-heteroaryl wherein this heteroaryl is 5- to 10-membered and comprises 1, 2 or 3 heteroatoms each individually selected from among N, O and S; whereby—in case that R7 is not hydrogen—R7 may optionally be substituted by 1, 2 or 3 residues R8 that are individually selected from the group consisting of hydrogen; -oxo; hydroxy; —C1-6-alkyl; —C1-6-haloalkyl; —NR9R10, -Q, —NR9Q, 3- to 6-membered saturated or partially unsaturated cycloalkyl; whereby—in case that R8 is not hydrogen—R8 may optionally be substituted by 1, 2 or 3 residues selected from hydrogen, -oxo, hydroxy, —C1-6-alkyl, halogen, —C1-6-haloalkyl, —O—C1-6-alkyl, —C1-3-alkylene-O—C1-3-alkyl, wherein each of R9, R10 and R11 is individually from one another selected from the group consisting of hydrogen, —C1-6-alkyl, —C3-8-cycloalkyl, —C1-6-alkyl-C3-8-cycloalkyl and phenyl, and wherein each Q is individually selected either from a 5- to 10-membered saturated or partially unsaturated heterocyclus comprising 1, 2 or 3 heteroatoms each individually selected from among N, O or S or from a 5- to 10-membered heteroaryl comprising 1, 2 or 3 heteroatoms each individually selected from among N, O and S; whereby Q is attached to the rest of the molecule either via a carbon atom or via an nitrogen atom, the N-oxides of the aforementioned compounds, particularly the 1-naphthyridinyl-oxides of the aforementioned compounds, and the pharmaceutically acceptable salts of the aforementioned compounds wherein said disease is selected from asthma, COPD, allergic rhinitis, allergic dermatitis and rheumatoid arthritis. |
