Quinolone derivative or salt thereof
A platelet aggregation inhibitor comprising a quinolone derivative or a pharmaceutically acceptable salt thereof as an active ingredient, and a novel quinolone derivative or a pharmaceutically acceptable salt thereof useful as a platelet aggregation inhibitor.
1. A platelet aggregation inhibitor comprising a quinolone derivative represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient:
[the symbols in the formula have the following meanings:
X: C—R 7 or N;
Y: C—R 6 or N;
R 11 : —H;
R 12 : a lower alkyl which is substituted;
R 2 : a lower alkyl or a cycloalkyl;
R 3 : a halogen;
R 4 : a cycloalkyl;
R 5 :—H;
R 6 : —H;
R 7 : —H.
2. A P2Y12 inhibitor comprising the compound according to claim 1 as an active ingredient.
3. A method for inhibiting platelet aggregation in an individual, comprising administering a therapeutically effective amount of the compound of claim 1 , and at least one pharmaceutically acceptable carrier, to the individual.
4. A method for inhibiting P2Y12 in an individual needing therapy for circulatory diseases involving thrombosis via platelet aggregation, comprising administering a therapeutically effective amount of the compound of claim 1 , and at least one pharmaceutically acceptable carrier, to the individual.
5. A quinolone derivative represented by the formula (I-a) or a pharmaceutically acceptable salt thereof:
[the symbols in the formula have the following meanings:
X: C—R 7 or N;
Y: C—R 6 or N;
R 11 : —H;
R 12 : a lower alkyl, which is substituted;
R 2 : a lower alkyl or a cycloalkyl;
R 3 : a halogen;
R 4 : a cycloalkyl;
R 5 : —H;
R 6 : —H;
R 7 : —H.
6. The compound according to claim 5 , wherein X is CH.
7. The compound according to claim 6 , wherein R 12 is a lower alkyl substituted with one or more substituent groups selected from Group Q, wherein at least one of the substituent groups is selected from Group P:
Group P: —CO 2 H, —SO 3 H, —P(O)(OH) 2 , and —OP(O)(OH) 2 ; and
Group Q: —F, —OH, —CO 2 H, —SO 3 H, —P(O)(OH) 2 , and —OP(O)(OH) 2 .
8. The compound according to claim 5 , which is
(2S)-2-({[7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]carbonyl}amino)butanedioic acid,
(2S)-2-({[7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl[carbonyl}amino)pentanedioic acid,
(2S)-2-({[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]carbonyl}amino)pentanedioic acid or
(2S)-2-({[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydrocinnolin-3-yl]carbonyl}amino)pentanedioic acid,
or a pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition comprising a compound according to any one of claims 5 , 6 , 7 or 8 and a pharmaceutically acceptable carrier.
10. The pharmaceutical composition according to claim 9 , which is a platelet aggregation inhibitor.
11. The pharmaceutical composition according to claim 9 , which is a P2Y12 inhibitor.
12. A method for inhibiting platelet aggregation in an individual, comprising administering a therapeutically effective amount of the compound of any one of claims 5 , 6 , 7 or 8 , and at least one pharmaceutically acceptable carrier, to the individual.
13. A method for inhibiting P2Y12 in an individual needing therapy for circulatory diseases involving thrombosis via platelet aggregation, comprising administering a therapeutically effective amount of the compound of any one of claims 5 , 6 , 7 or 8 , and at least one pharmaceutically acceptable carrier, to the individual.
14. The compound according to claim 5 , which is
[2-({[7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]carbonyl}amino)ethyl]phosphonic acid,
2-({[7-(cyclohexylamino)-1-cyclopentyl-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]carbonyl}amino)ethyl dihydrogen phosphate,
[2-({[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]carbonyl}amino)-1,1-difluoroethyl]phosphonic acid,
[2-({[7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydrocinnolin-3-yl]carbonyl}amino)ethyl]phosphonic acid,
[2-({[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydrocinnolin-3-yl]carbonyl}amino)ethyl]phosphonic acid, or
[2-({[7-(cyclohexylamino)-1-(1-ethylpropyl)-6-fluoro-4-oxo-1,4-dihydroquinolin-3-yl]carbonyl}amino)ethyl]phosphonic acid,
or a pharmaceutically acceptable salt thereof.