VEGFR-2 and VEGFR-3 inhibitory anthranilamide pyridones
View Patent ↗Novel VEGFR-2 and VEGFR-3 inhibitory anthranilamide pyridones and their use as pharmaceutical agents for treating diseases that are triggered by persistent angiogenesis are selected.
1. A compound of formula I
in which
A stands for an aryl or unsubstituted heteroaryl moiety, wherein the heteroaryl is not an indazole group,
X stands for hydrogen or fluorine,
R 1 and R 2 , independently of one another, stand for hydrogen, halogen, C 1 –C 12 -alkyl, C 1 –C 12 -alkoxy-C 1 –C 10 -alkylene, C 3 –C 10 -cycloalkyl or halo-C 3 –C 10 -cycloalkyl, and
Y stands for a bond or for oxygen or for the group —S—, —S(O)— or —SO 2 —,
or a salt thereof.
2. A compound of formula I according to claim 1 , in which
A stands for a phenyl or pyridyl,
X stands for hydrogen or fluorine,
R 2 and R 2 , independently of one another, stand for hydrogen, halogen, C 1 –C 12 -alkyl, C 1 –C 12 -alkoxy-C 1 –C 10 -alkylene, C 3 –C 10 -cycloalkyl or halo-C 3 –C 10 -cycloalkyl and
Y stands for a bond or for oxygen or for the group —S—, —S(O)— or —SO 2 —,
or a salt thereof.
3. A compound of formula I according to claim 1 , in which
A stands for a phenyl,
X stands for hydrogen or fluorine,
R 1 and R 2 , independently of one another, stand for hydrogen, halogen, C 1 –C 12 -alkyl, C 1 –C 12 -alkoxy-C 1 –C 10 -alkylene, C 3 –C 10 -cycloalkyl or halo-C 3 –C 10 -cycloalkyl, and
Y stands for a bond or for oxygen or for the group —S—, —S(S)— or —SO 2—,
or a salt thereof.
4. A compound of formula I according to claim 1 , in which
A stands for a phenyl,
X stands for hydrogen,
R 1 and R 2 , independently of one another, stand for hydrogen, halogen, C 1 –C 12 -alkyl, C 1 –C 12 -alkoxy-C 1 –C 10 -alkylene, C 3 –C 10 -cycloalkyl or halo-C 3 –C 10 -cycloalkyl, and
Y stands for a bond or for oxygen or for the group —S—, —S(O)— or —SO 2 —,
or a salt thereof.
5. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
6. A compound according to claim 1 , which is an isomer, enantiomer, or diastereomer of said compound.
7. A method for treating Kaposi's sarcoma, leukemia, diabetic retinopathy, neovascular glaucoma, and arteriosclerosis comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition according to claim 5 .
8. A compound according to claim 1 , wherein at least one of the Y groups is oxygen, —S—, —S(O)— or —SO 2 —.
9. A compound according to claim 1 , wherein at least one of the Y groups is oxygen or —S—.
10. A compound according to claim 1 , wherein A stands for: cyclopropenyl, cyclopentadienyl, phenyl, tropyl, cyclooctadienyl, indenyl, naphthyl, azulenyl, biphenyl, fluorenyl, anthracenyl, thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzimidazolyl, indolyl, isoindolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolyl, isoquinolyl, azocinyl, indolizinyl, purinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxaliriyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, or oxepinyl.
11. A compound according to claim 1 , which is
or
wherein
is
12. Acompound according to claim 1 , which is
13. A compound according to claim 1 , wherein R 1 or R 2 is —OCF 3 ,—OMe, —OiProp, —OEt, —OnBu, —OCH 2 CF 3 , —OH, —SCF 3 , —OCH 2 CH 2 OMe, —OCHF 2 , —OCH 2 CH 2 CF 3 , —OCH 2 CF 2 CF 3 , —OCH(CF 3 ) 2 , —OCH(CF 3 ) 2 CH 3 , —Cl, or —OCH 2 CH(CH 3 ) 2 .
14. A pharmaceutical composition comprising a compound according to claim 11 and a pharmaceutically acceptable carrier.