RU2002111005A - Naphthyridine derivatives - Google Patents

Claims (8)

1. The naphthyridine derivative represented by the following general formula (I ’), or a pharmaceutically acceptable salt thereof

where R ¹ is R ⁰ , lower alkylene-cycloalkyl or cycloalkyl; R ⁰ is lower alkyl; R ² , R ³ and R ⁴ —H, R ⁰ , halogen, lower alkylene — OH, lower alkylene — SH, lower alkylene — O — R ⁰ , lower alkylene — SR ⁰ , lower alkylene — O — CO — R ⁰ , lower alkylene-S — CO — R ⁰ , —OH, —O — R ⁰ , —SR ⁰ , —SO — R ⁰ , —SO ₂ —R ⁰ , —NH ₂ , —NHR ⁰ , —NR $\genfrac{}{}{0ex}{}{\text{0}}{\text{2}}$ , -cycloalkyl, -CO-R ⁰ or -CH = N-OR ⁹ , which may be the same or different from each other; R ⁹ is H, R ⁰ or lower alkylene-aryl; R ⁵ is cycloalkyl which may be substituted by a group selected from R ¹⁰ , cycloalkenyl which may be substituted by a group selected from R ¹⁰ , a heterocyclic group which may be substituted by a group selected from R ¹⁰ , or phenyl which may be substituted a group selected from R ¹⁰ ; R ⁶ is OH, -OR ⁷ , -COOH, -COOR ⁷ , -CONH ₂ , -CONHR ⁷ , -CON (R ⁷ ) ₂ , -O-COR ⁷ , -O-COOR ⁷ , -CHO, -COR ⁷ , -NH ₂ , -NHR ⁷ , -N (R ⁷ ) ₂ , -NHCOR ⁷ , -N (R ⁷ ) ₂ COR ⁷ , -NHSO ₂ R ⁷ , -N (R ⁷ ) SO ₂ R ⁷ , -CN , —NHCOOR ⁷ , —N (R ⁷ ) COOR ⁷ , —C (NH) NH ₂ , —NHC (NH) NH ₂ or —N (R ⁷ ) C (NH) NH ₂ , or a group of the formula —YR ⁸ ; R ⁷ is lower alkyl which may be substituted by a group selected from the group consisting of —OH, phenyl, halogen, —OR ⁰ , —CO ₂ H, —CO ₂ R ⁰ , —NH ₂ , —NHR ⁰ , - Nr $\genfrac{}{}{0ex}{}{\text{0}}{\text{2}}$ , -NO ₂ , -CN and -COR ⁰ ; R ⁸ is cycloalkyl which may be substituted by a group selected from R ¹⁰ , aryl which may be substituted by a group selected from R ¹⁰ , or a heterocyclic group which may be substituted by a group selected from R ¹⁰ ; R ¹⁰ is OH, -phenyl, -halogen, -OR ⁰ , -CO ₂ H, -CO ₂ R ⁰ , -NH ₂ , -NHR ⁰ , -NR $\genfrac{}{}{0ex}{}{\text{0}}{\text{2}}$ , —NO ₂ , —CN or —COR ⁰ , or a group described in R ⁷ ; Y is a bond, -O-, -COO-, -CONH-, -CON (R ⁷ ) -, -O-CO-, -O-COO-, -CO-, -NH-, -N (R ⁷ ) -, -NHCO-, -N (R ⁷ ) CO-, -NHCOO-, -N (R ⁷ ) COO-, -NHSO ₂ - or -N (R ⁷ ) SO ₂ -; X is a bond or lower alkylene or lower alkenylene, provided that if X is a bond, then R ⁶ is —YR ⁸ and Y is a bond. 2. The naphthyridine derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein X is a bond or lower alkylene and R ⁶ is —OH, —COOH, —COOR ⁷ , —O — COR ⁷ , —NH ₂ , —NHR ⁷ , - N (R ⁷ ) ₂ , —C (NH) NH ₂ , —NHC (NH) NH _2, or —N (R ⁷ ) C (NH) NH ₂ , or a group of the formula —YR ⁸ . 3. The naphthyridine derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein R ⁵ is cyclohexyl or phenyl substituted with halogen. 4. The naphthyridine derivative or a pharmaceutically acceptable salt thereof according to claim 1, which is selected from the group consisting of 3- (2-amidinoethyl) -4- (3-chlorophenyl) -1-ethyl-7-methyl-1, 8-naphthyridine- 2 (1H) -one, 4- (3-chlorophenyl) -1-ethyl-3- (2-guanidinoethyl) -7-methyl-1,8-naphthyridin-2 (1H) -one, 4-cyclohexyl-1- ethyl-7-methyl-3- [2- (1H-tetrazol-5-yl) ethyl] -1,8-naphthyridin-2 (1H) -one, 4- (3-chlorophenyl) -1-ethyl-7- methyl-3- [3- (1H-tetrazol-5-yl) propyl] -1,8-naphthyridin-2 (1H) -one, 4- (3-bromophenyl) -1-ethyl-7-methyl-3- [2- (1H-tetrazol-5-yl) ethyl] -1,8-naphthyridin-2 (1H) -one, 3- [4- (3-chlorophenyl) -1-ethyl-7-methyl-2-oxo -1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid, 3- (4-c clohexyl-1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid, 3- [4- (3-chlorophenyl) -1-ethyl-7- methyl-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl] benzoic acid, 3- [4- (3-chloro-phenyl) -1-ethyl-7- (hydroxyiminomethyl) -2- oxo-1,2-dihydro-1,8-naphthyridin-3-yl] propanoic acid, 3- [7-chloro-4- (3-chloro-phenyl) -1-ethyl-2-oxo-1,2- dihydro-1,8-naphthyridin-3-yl] propanoic acid, 3- [1-ethyl-7-methyl-4- (3-methylphenyl) -2-oxo-1,2-dihydro-1,8-naphthyridin- 3-yl] propanoic acid, 4- (3-chloro-phenyl) -1-ethyl-7-methyl-3- (piperidin-4-yl) -1,8-naphthyridin-2 (1H) -one and 1- {2- [4- (3-chlorophenyl) -1-ethyl-7-methyl-2-oxo-1,2-dihydro-1,8-naphthyrid in-3-yl] ethyl} piperidin-4-carboxylic acid. 5. A pharmaceutical composition that contains the naphthyridine derivative of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 6. A pharmaceutical composition that contains a naphthyridine derivative represented by the following general formula (I) or a pharmaceutically acceptable salt thereof as a type IV phosphodiesterase inhibitor and a pharmaceutically acceptable carrier

where R ¹ is R ⁰ , lower alkylene-cycloalkyl or cycloalkyl; R ⁰ is lower alkyl; R ² , R ³ and R ⁴ —H, R ⁰ , halogen, lower alkylene — OH, lower alkylene — SH, lower alkylene — O — R ⁰ , lower alkylene — SR ⁰ , lower alkylene — O — CO — R ⁰ , lower alkylene-S — CO — R ⁰ , —OH, —O — R ⁰ , —SR ⁰ , —SO — R ⁰ , —SO ₂ —R ⁰ , —NH ₂ , —NHR ⁰ , —NR $\genfrac{}{}{0ex}{}{\text{0}}{\text{2}}$ cycloalkyl, —CO — R ⁰ or —CH = N — OR ⁹ , which may be the same or different from each other; R ⁹ is H, R ⁰ or lower alkylene-aryl; R ⁵ is cycloalkyl which may be substituted by a group selected from R ¹⁰ , cycloalkenyl which may be substituted by a group selected from R ¹⁰ , a heterocyclic group which may be substituted by a group selected from R ¹⁰ , or phenyl which may be substituted a group selected from R ¹⁰ ; R ⁶ is OH, -OR ⁷ , -COOH, -COOR ⁷ , -CONH ₂ , -CONHR ⁷ , -CON (R ⁷ ) ₂ , -O-COR ⁷ , -O-COOR ⁷ , -CHO, -COR ⁷ , -NH ₂ , -NHR ⁷ , -N (R ⁷ ) ₂ , -NHCOR ⁷ , -N (R ⁷ ) COR ⁷ , -NHSO ₂ R ⁷ , -N (R ⁷ ) SO ₂ R ⁷ , -CN, —NHCOOR ⁷ , —N (R ⁷ ) COOR ⁷ , —C (NH) NH ₂ , —NHC (NH) NH _2, or —N (R ⁷ ) C (NH) NH ₂ , or a group of the formula —YR ⁸ ; R ⁷ is lower alkyl which may be substituted by a group selected from the group consisting of —OH, phenyl, halogen, —OR ⁰ , —CO ₂ H, —CO ₂ R ⁰ , —NH ₂ , —NHR ⁰ , —NR $\genfrac{}{}{0ex}{}{\text{0}}{\text{2}}$ , -NO ₂ , -CN and -COR ⁰ ; R ⁸ is cycloalkyl which may be substituted by a group selected from R ¹⁰ , aryl which may be substituted by a group selected from R ¹⁰ , or a heterocyclic group which may be substituted by a group selected from R ¹⁰ ; R ¹⁰ —OH, phenyl, halogen, —OR ⁰ , —CO ₂ H, —CO ₂ R ⁰ , —NH ₂ , —NHR ⁰ , —NR $\genfrac{}{}{0ex}{}{\text{0}}{\text{2}}$ , —NO ₂ , —CN or —COR ⁰ , or a group described in R ⁷ ; Y is a bond, -O-, -COO-, -CONH-, -CON (R ⁷ ) -, -O-CO-, -O-COO-, -CO-, -NH-, -N (R ⁷ ) -, -NHCO-, -N (R ⁷ ) CO-, -NHCOO-, -N (R ⁷ ) COO-, -NHSO ₂ - or -N (R ⁷ ) SO ₂ -; X is a bond or lower alkylene, or lower alkenylene. 7. The pharmaceutical composition according to claim 6, which is an agent for the prevention or treatment of respiratory diseases. 8. The pharmaceutical composition according to claim 7, which is an agent for the prevention or treatment of bronchial asthma.