c-Met modulators and method of use
View Patent ↗The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.
1. A compound of formula A-B-C, or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein:
A is:
B is:
and
C is:
and
wherein:
R 2 is selected from —H, halogen, trihalomethyl, —CN, —NH 2 , —NO 2 , —OR 3 , —NR 3 R 3 , —S(O) 0-2 R 3 , —SO 2 NR 3 R 3 , —CO 2 R 3 , —C(O)NR 3 R 3 , —N(R 3 )SO 2 R 3 , —N(R 3 )C(O)R 3 , —N(R 3 )CO 2 R 3 , —C(O)R 3 , and optionally substituted lower alkyl;
q is 0 to 2;
each R 3 is independently selected from —H, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl; or, two R 3 , together with the nitrogen to which they are attached, form a four- to seven-membered heteroalicyclic, said four- to seven-membered heteroalicyclic optionally containing one additional heteroatom; when one said additional heteroatom is a nitrogen, then said nitrogen is optionally substituted with a group selected from —H, trihalomethyl, —SO 2 R 5 , —SO 2 NR 5 R 5 , —CO 2 R 5 , —C(O)NR 5 R 5 , —C(O)R 5 , and optionally substituted lower alkyl;
A 1 is ═C(H)—;
A 2 is either ═N— or ═C(H)—;
R 5 is —H or optionally substituted lower alkyl;
E 1 is selected from —O—, —CH 2 —, —N(R 5 )—, and —S(O) 0-2 —;
Q is a five- to ten-membered ring system, optionally substituted with between zero and four of R 20 ; and
R 20 is selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —NH 2 , —OR 3 , —NR 3 R 3 , —S(O) 0-2 R 3 , —SO 2 NR 3 R 3 , —CO 2 R 3 , —C(O)NR 3 R 3 , —N(R 3 )SO 2 R 3 , —N(R 3 )C(O)R 3 , —N(R 3 )CO 2 R 3 , —C(O)R 3 , and optionally substituted lower alkyl.
2. The compound according to claim 1 , wherein Q is selected from phenyl, napthyl, 1,2,3,4-tetrahydronaphthyl, indanyl, benzodioxanyl, benzofuranyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroisoquinolyl, pyrrolyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, tetrahydropyridinyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolinyl, oxazolidinyl, triazolyl, isoxazolyl, isoxazolidinyl, thiazolyl, thiazolinyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, octahydroindolyl, octahydroisoindolyl, quinolyl, isoquinolyl, benzimidazolyl, thiadiazolyl, benzopyranyl, benzothiazolyl, benzoxazolyl, furyl, thienyl, benzothieliyl, and oxadiazolyl; each optionally substituted with between one and four of R 20 ; wherein each R 20 is independently selected from —H, halogen, trihalomethyl, —CN, —NO 2 , —NH 2 , —OR 3 , —NR 3 R 3 , —CO 2 R 3 , —C(O)NR 3 R 3 , —N(R 3 )SO 2 R 3 , —N(R 3 )C(O)R 3 , —N(R 3 )CO 2 R 3 , —C(O)R 3 , and optionally substituted lower alkyl.
3. The compound according to claim 1 , wherein A is:
4. The compound according to claim 1 , wherein B is:
5. The compound according to claim 1 , wherein C is:
6. The compound according to claim 5 , wherein R 2 is selected from halogen, trihalomethyl, —CN, —NO 2 , —OR 3 , —NR 3 R 3 , —CO 2 R 3 , —C(O)NR 3 R 3 , —N(R 3 )C(O)R 3 , —N(R 3 )CO 2 R 3 , —C(O)R 3 , and optionally substituted lower alkyl.
7. The compound according to claim 6 , wherein R 2 is halogen.
8. The compound according to claim 7 , wherein R 2 is either fluorine or chlorine.
9. The compound according to claim 5 , wherein R 2 is hydrogen.
10. A compound selected from the group consisting of:
Name
Structure
ethyl [(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl) amino](oxo)acetate
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (phenylmethyl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (2-phenylethyl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- phenylethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (2-morpholin-4- ylethyl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- {2-[4-(methyloxy) phenyl]ethyl}ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (2,3-dihydro-1H-inden-1- yl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (2,3-dihydro-1H-inden-2- yl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (1,2,3,4-tetrahydronaphthalen- 1-yl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- [(2S)-1,2,3,4- tetrahydronaphthalen-2- yl]ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- [2-(4-methylphenyl) ethyl]ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (2-phenylpropyl) ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- [2-(4-chlorophenyl) ethyl]ethanediamide
ethyl [(6-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-5-chloropyridin-3- yl)amino](oxo)acetate
N-(6-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-5-chloropyridin-3- yl)-N′-(2-phenylethyl) ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (1,2,3,4-tetrahydronaphthalen- 2-yl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- [2-(1-methylpyrrolidin-2- yl)ethyl]ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- [2-(phenyloxy) ethyl]ethanediamide
N′-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N- methyl-N-(2-phenylethyl) ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- {[3-(trifluoromethyl) phenyl]methyl}ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- {2-[3-(trifluoromethyl) phenyl]ethyl}ethanediamide
N-{3-fluoro-4-[(6- (methyloxy)-7-{[(1- methylpiperidin-4- yl)methyl]oxy}quinolin-4- yl)oxy]phenyl}-N′-(2- phenylethyl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- (1,2,3,4- tetrahydroisoquinolin-1- ylmethyl)ethanediamide
N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N′- [(2-methyl-1,2,3,4- tetrahydroisoquinolin-1- yl)methyl]ethanediamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- phenethyl-oxalamide
N-[4-(6,7-Dimethoxy- quinolin-4-yloxy)-3-fluoro- phenyl]-N′-(2-isopropyl- 1,2,3,4-tetrahydro- isoquinolin-1-ylmethyl)- oxalamide
N-[4-(6,7-Dimethoxy- quinolin-4-yloxy)-3-fluoro- phenyl]-N′-(2-ethyl-1,2,3,4- tetrahydro-isoquinolin-1- ylmethyl)-oxalamide
N-{4-[7-(3-Diethylamino- propoxy)-6-methoxy- quinolin-4-yloxy]-3-fluoro- phenyl}-N′-phenethyl- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (3-morpholin-4-yl-propoxy)- quinolin-4-yloxy]-phenyl}-N′- phenethyl-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (3-piperidin-1-yl-propoxy)- quinolin-4-yloxy]-phenyl}-N′- phenethyl-oxalamide
N-{4-[7-(2-Diethylamino- ethoxy)-6-methoxy-quinolin- 4-yloxy]-3-fluoro-phenyl}-N′- phenethyl-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-methyl-N′- phenethyl-oxalamide
2-(3,4-Dihydro-1H- isoquinolin-2-yl)-N-{3-fluoro- 4-[6-methoxy-7-(1-methyl- piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-acetamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-2-(3-phenyl-pyrrolidin-1- yl)-acetamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-2-(2-phenyl-morpholin-4- yl)-acetamide
N-(2-Dimethylamino-2- phenyl-ethyl)-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-oxo-2-phenyl-ethyl)- oxalamide
N-Benzyl-N′-{3-fluoro-4-[6- methoxy-7-(1-methyl- piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(2-fluoro-phenyl)-ethyl]- oxalamide
N-[2-(3-Chloro-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(2-methoxy-phenyl)-ethyl]- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-pyridin-3-yl-ethyl)- oxalamide
N-Benzyl-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(2,5-Dimethoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-{piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(2-trifluoromethyl-phenyl)- ethyl]-oxalamide
N-[2-(2-Ethoxy-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(2,4-Dimethyl-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1S-phenyl-2-p-tolyl-ethyl)- oxalamide
N-[2-(4-Chloro-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamic acid
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(3-fluoro-phenyl)-ethyl]- oxalamide
N-[2-(2-Chloro-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(3-methoxy-phenyl)-ethyl]- oxalamide
N-(1,2-Diphenyl-ethyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-[2-(2,4-Dichloro-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(3,4-Dimethoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(4-Ethyl-phenyl)-ethyl]- N′-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-[2-(4-Ethoxy-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(4-Ethoxy-3-methoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(4-phenoxy-phenyl)-ethyl]- oxalamide
N-[2-(3-Ethoxy-4-methoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-pyridin-2-yl-ethyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-pyridin-4-yl-ethyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(4-fluoro-phenyl)-ethyl]- oxalamide
N-[2-(2-Bromo-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(2-Chloro-6-fluoro- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2R-phenyl-propyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- indan-1-yl-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-isobutyl- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-{3-methyl- butyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-(2R- phenyl-propyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-(2-phenyl- propyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-indan-2-yl- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1R-phenyl-ethyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1S-phenyl-ethyl)-oxalamide
N-[2-(3-Bromo-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(2,6-Dichloro-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(2,4-Dichloro-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-(2-Benzo[1,3]dioxol-5-yl- ethyl)-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(3-Bromo-4-methoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(3,5-Dimethoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-o-tolyl-ethyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-m-tolyl-ethyl)-oxalamide
N-[2-(3-Ethoxy-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(3,4-Dimethyl-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(2,5-Dimethyl-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(3-Chloro-4-propoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(4-Butoxy-3-chloro- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(4-tert-Butyl-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(4-sulfamoyl-phenyl)- ethyl]-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(4-hydroxy-3-methoxy- phenyl)-ethyl]-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(3-hydroxy-4-methoxy- phenyl)-ethyl]-oxalamide
N-(2,4-Dichloro-benzyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (4-fluoro-2-trifluoromethyl- benzyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1-p-tolyl-ethyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (3-fluoro-4-trifluoromethyl- benzyl)-oxalamide
N-(3-Chloro-4-fluoro-benzyl)- N′-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [1-(3-methoxy-phenyl)-ethyl]- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1-naphthalen-2-yl-ethyl)- oxalamide
N-(4-Chloro-3- trifluoromethyl-benzyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1-p-tolyl-ethyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (6-trifluoromethyl-pyridin-3- ylmethyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-methyl-benzyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (3-methyl-benzyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (4-fluoro-3-trifluoromethyl- benzyl)-oxalamide
N-(3,5-Dichloro-benzyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1R,2,3,4-tetrahydro- naphthalen-1-yl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1S,2,3,4-tetrahydro- naphthalen-1-yl)-oxalamide
N-Cyclopentyl-N′-{3-fluoro- 4-[6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[1-(4-Bromo-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-(2-Fluoro-benzyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-[2-(3,4-Dichloro-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-(4-Fluoro-benzyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-(2,3-Difluoro-benzyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-phenoxy-ethyl)-oxalamide
N-(2,2-Diphenyl-ethyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [2-(4-methoxy-phenyl)-ethyl]- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-phenyl-propyl)-oxalamide
N-[2-(4-Bromo-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{4-[7-(1-Ethyl-piperidin-4- ylmethoxy)-6-methoxy- quinolin-4-yloxy]-3-fluoro- phenyl}-2-oxo-2-(2-phenyl- morpholin-4-yl)-acetamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (3-fluoro-5-trifluoromethyl- benzyl)-oxalamide
N-(3,5-Difluoro-benzyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-(2-Chloro-5- trifluoromethyl-benzyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-[4-(6,7-Dimethoxy- quinolin-4-yloxy)-3-fluoro- phenyl]-N′-(2-dimethylamino- 2-phenyl-ethyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (4-methoxy-benzyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (4-trifluoromethyl-benzyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (3-methoxy-benzyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (3-trifluoromethyl-benzyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (3-trifluoromethoxy-benzyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-methoxy-benzyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-trifluoromethyl-benzyl)- oxalamide
N-(3-Chloro-benzyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-trifluoromethoxy-benzyl)- oxalamide
N-(2-Chloro-benzyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (4-trifluoromethoxy-benzyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-(4- methoxy-benzyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-(4- trifluoromethyl-benzyl)- oxalamide
N-{4-[7-(Azetidin-3- ylmethoxy)-6-methoxy- quinolin-4-yloxy]-3-fluoro- phenyl}-N′-phenethyl- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-azetidin-3- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-phenethyl- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-hydroxy-2-phenyl-ethyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1R-phenyl-propyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (1R-phenyl-propyl)- oxalamide
N-(3,4-Difluoro-benzyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-(2,6-Difluoro-benzyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-[2-(4- fluoro-phenyl)-ethyl]- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N′-phenyl- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (3-fluoro-phenyl)-oxalamide
N-(4-Chloro-3-fluoro- phenyl)-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-(3,4-Dimethoxy-phenyl)- N′-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (3-methyl-butyl)-oxalamide
N-(3,3-Dimethyl-butyl)-N′- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-(4-Chloro-benzyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-(3,5-Dimethoxy-benzyl)- N′-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-(4-Butyl-benzyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-p-tolyl-ethyl)-oxalamide
N-(3,5-Bis-trifluoromethyl- benzyl)-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- pyrazin-2-ylmethyl-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- pyridin-2-ylmethyl-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-fluoro-3-trifluoromethyl- benzyl)-oxalamide
N-[2-(2-Bromo-6-methoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-[2-(3,4-Dimethoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N-methyl- oxalamide
N-[2-(5-Bromo-2-methoxy- phenyl)-ethyl]-N′-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-fluoro-5-trifluoromethyl- benzyl)-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- [1-(4-fluoro-phenyl)-ethyl]- oxalamide
N-(1S-Benzyl-2-oxo-2- pyrrolidin-1-yl-ethyl)-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-[2-(4-Amino-phenyl)- ethyl]-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
2-(4-Benzyl-piperidin-1-yl)- N-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-acetamide
N-Ethyl-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- isopropyl-oxalamide
N-Butyl-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-methoxy-ethyl)-oxalamide
N-Cyclopropylmethyl-N′-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N′- (2-morpholin-4-yl-ethyl)- oxalamide
N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-2-pyrrolidin-1-yl- acetamide
N-Ethyl-N′-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N-methyl- oxalamide
11. A pharmaceutical composition comprising a compound according to claim 1 or 10 , and a pharmaceutically acceptable carrier.