US2007135489A1PendingUtilityA1
Vegfr-2 and vegfr-3 inhibitory anthranilamide pyridones
Est. expiryJun 13, 2023(expired)· nominal 20-yr term from priority
Inventors:Andreas HuthMartin KruegerLudwig ZornStuart InceRolf BohlmannKarl-Heinz ThierauchAndreas MenradMartin HabereyHolger Hess-Stumpp
C07D 213/64
56
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Claims
Abstract
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.
Claims
exact text as granted — not AI-modified1 - 11 . (canceled)
12 . A method for treating a tumor or metastasis growth, psoriasis, Kaposi's sarcoma, restenosis, stent-induced restenosis, endometriosis, Crohn's disease, Hodgkin's disease, leukemia, arthritis, rheumatoid arthritis, hemangioma, angiofibroma, an eye disease, diabetic retinopathy, neovascular glaucoma, a renal disease, glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombic microangiopathic syndrome, a transplant rejection, glomerulopathy, a fibrotic disease, cirrhosis of the liver, a mesangial cell proliferative disease, arteriosclerosis, an injury to nerve tissue, senile keratosis or contact dermatitis; a method for inhibiting the reocclusion of a vessel after balloon catheter treatment, vascular prosthetics or use of a mechanical device to keep vessels open, or use of a stent; a method for immunosuppression or supporting scar-free healing; or
a method for inhibiting tyrosine kinases selected from KDR, FLT-1 and FLT-4 or inhibiting VEGFR kinase 3 of lymphangiogenesis comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula I in which A stands for an aryl or heteroaryl, 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, halo-C 1 -C 10 -alkyl, 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.
13 . A method according to claim 12 , which is for treating a tumor or metastasis growth, psoriasis, Kaposi's sarcoma, restenosis, stent-induced restenosis, endometriosis, Crohn's disease, Hodgkin's disease, leukemia, arthritis, rheumatoid arthritis, hemangioma, angiofibroma, an eye disease, diabetic retinopathy, neovascular glaucoma, a renal disease, glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombic microangiopathic syndrome, a transplant rejection, glomerulopathy, a fibrotic disease, cirrhosis of the liver, a mesangial cell proliferative disease, arteriosclerosis, an injury to nerve tissue, senile keratosis or contact dermatitis; a method for inhibiting the reocclusion of a vessel after balloon catheter treatment, vascular prosthetics or use of a mechanical device to keep vessels open, or use of a stent; a method for immunosuppression or supporting scar-free healing.
14 . A method according to claim 12 , which is for inhibiting tyrosine kinases selected from KDR, FLT-1 and FLT-4.
15 . A method according to claim 12 , which is for inhibiting VEGFR kinase 3 of lymphangiogenesis.
16 . A method according to claim 12 , which is for treating psoriasis, Kaposi's sarcoma, stent-induced restenosis, endometriosis, Crohn's disease, Hodgkin's disease, leukemia, rheumatoid arthritis, hemangioma, angiofibroma, diabetic retinopathy, neovascular glaucoma, glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombic microangiopathic syndrome, a transplant rejection, glomerulopathy, cirrhosis of the liver, arteriosclerosis; or a method for inhibiting the reocclusion of a vessel after balloon catheter treatment, vascular prosthetics or use of a mechanical device to keep vessels open, or use of a stent; or a method for supporting scar-free healing.
17 . A method according to claim 12 , wherein at least one of the Y groups is oxygen, —S—, —S(O)— or —SO 2 —.
18 . A method according to claim 12 , wherein at least one of the Y groups is oxygen or —S—.
19 . A method according to claim 12 , 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, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, or oxepinyl.
20 . A method according to claim 12 , 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 .
21 . A method according to claim 12 , wherein
A stands for a phenyl or pyridyl, 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.
22 . A method according to claim 12 , wherein
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 2 -alkyl, C 1 -C 12 -alkoxy-C 1 -C 10 -alkylene, halo-C 1 -C 10 -alkyl, 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.
23 . A method according to claim 12 , wherein
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.
24 . A method according to claim 12 , wherein
A stands for an aryl or heteroaryl, 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.
25 . A method according to claim 12 , wherein the compound of formula I is an isomer, enantiomer, or diastereomer of said compound.
26 . A method according to claim 12 , wherein the administration is selected from enteral, parenteral and oral administration.
27 . A method according to claim 12 , wherein the compound of formula I is
28 . A method according to claim 12 , wherein the compound of formula I is
29 . A method according to claim 12 , wherein A stands for an aryl or unsubstituted heteroaryl moiety.
30 . A method according to claim 24 , wherein A stands for an aryl or unsubstituted heteroaryl moiety.Cited by (0)
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