Details for Patent: 8,476,298

Title:	c-Met modulators and method of use
Abstract:	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.
Inventor(s):	Bannen; Lynne Canne (Pacifica, CA), Chan; Diva Sze-Ming (San Francisco, CA), Chen; Jeff (San Francisco, CA), Forsyth; Timothy Patrick (Hayward, CA), Huynh; Tai Phat (Oakland, CA), Jammalamadaka; Vasu (Pleasanton, CA), Khoury; Richard George (Redwood City, CA), Leahy; James William (San Leandro, CA), Mac; Morrisson B. (San Francisco, CA), Mann; Larry W. (Richland, MI), Nuss; John M. (Danville, CA), Parks; Jason Jevious (Sacramento, CA), Takeuchi; Craig Stacy (Burlingame, CA), Wang; Yong (Foster City, CA), Xu; Wie (Danville, CA)
Assignee:	Exelixis, Inc. (South San Francisco, CA)
Filing Date:	May 24, 2007
Application Number:	11/753,503
Claims:	1. A compound of formula A-B-C, or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein: A is: ##STR00547## B is: ##STR00548## and C is: ##STR00549## and wherein: R.sup.2 is selected from --H, halogen, trihalomethyl, --CN, --NH.sub.2, --NO.sub.2, --OR.sup.3, --NR.sup.3R.sup.3, --S(O).sub.0-2R.sup.3, --SO.sub.2NR.sup.3R.sup.3, --CO.sub.2R.sup.3, --C(O)NR.sup.3R.sup.3, --N(R.sup.3)SO.sub.2R.sup.3, --N(R.sup.3)C(O)R.sup.3, --N(R.sup.3)CO.sub.2R.sup.3, --C(O)R.sup.3, and optionally substituted lower alkyl; q is 0 to 2; each R.sup.3 is independently selected from --H, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl; or, two R.sup.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.sub.2R.sup.5, --SO.sub.2NR.sup.5R.sup.5, --CO.sub.2R.sup.5, --C(O)NR.sup.5R.sup.5, --C(O)R.sup.5, and optionally substituted lower alkyl; A.sup.1 is .dbd.C(H)--; A.sup.2 is either .dbd.N-- or .dbd.C(H)--; R.sup.5 is --H or optionally substituted lower alkyl; E.sup.1 is selected from --O--, --CH.sub.2--, --N(R.sup.5)--, and --S(O).sub.0-2--; Q is a five- to ten-membered ring system, optionally substituted with between zero and four of R.sup.20; and R.sup.20 is selected from --H, halogen, trihalomethyl, --CN, --NO.sub.2, --NH.sub.2, --OR.sup.3, --NR.sup.3R.sup.3, --S(O).sub.0-2R.sup.3, --SO.sub.2NR.sup.3R.sup.3, --CO.sub.2R.sup.3, --C(O)NR.sup.3R.sup.3, --N(R.sup.3)SO.sub.2R.sup.3, --N(R.sup.3)C(O)R.sup.3, --N(R.sup.3)CO.sub.2R.sup.3, --C(O)R.sup.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.sup.20; wherein each R.sup.20 is independently selected from --H, halogen, trihalomethyl, --CN, --NO.sub.2, --NH.sub.2, --OR.sup.3, --NR.sup.3R.sup.3, --CO.sub.2R.sup.3, --C(O)NR.sup.3R.sup.3, --N(R.sup.3)SO.sub.2R.sup.3, --N(R.sup.3)C(O)R.sup.3, --N(R.sup.3)CO.sub.2R.sup.3, --C(O)R.sup.3, and optionally substituted lower alkyl. 3. The compound according to claim 1, wherein A is: ##STR00550## 4. The compound according to claim 1, wherein B is: ##STR00551## 5. The compound according to claim 1, wherein C is: ##STR00552## 6. The compound according to claim 5, wherein R.sup.2 is selected from halogen, trihalomethyl, --CN, --NO.sub.2, --OR.sup.3, --NR.sup.3R.sup.3, --CO.sub.2R.sup.3, --C(O)NR.sup.3R.sup.3, --N(R.sup.3)C(O)R.sup.3, --N(R.sup.3)CO.sub.2R.sup.3, --C(O)R.sup.3, and optionally substituted lower alkyl. 7. The compound according to claim 6, wherein R.sup.2 is halogen. 8. The compound according to claim 7, wherein R.sup.2 is either fluorine or chlorine. 9. The compound according to claim 5, wherein R.sup.2 is hydrogen. 10. A compound selected from the group consisting of: TABLE-US-00006 Name Structure ethyl [(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl) amino](oxo)acetate ##STR00553## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (phenylmethyl)ethanediamide ##STR00554## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (2-phenylethyl)ethanediamide ##STR00555## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- phenylethanediamide ##STR00556## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (2-morpholin-4- ylethyl)ethanediamide ##STR00557## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- {2-[4-(methyloxy) phenyl]ethyl}ethanediamide ##STR00558## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (2,3-dihydro-1H-inden-1- yl)ethanediamide ##STR00559## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (2,3-dihydro-1H-inden-2- yl)ethanediamide ##STR00560## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (1,2,3,4-tetrahydronaphthalen- 1-yl)ethanediamide ##STR00561## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- [(2S)-1,2,3,4- tetrahydronaphthalen-2- yl]ethanediamide ##STR00562## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- [2-(4-methylphenyl) ethyl]ethanediamide ##STR00563## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (2-phenylpropyl) ethanediamide ##STR00564## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- [2-(4-chlorophenyl) ethyl]ethanediamide ##STR00565## ethyl [(6-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-5-chloropyridin-3- yl)amino](oxo)acetate ##STR00566## N-(6-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-5-chloropyridin-3- yl)-N'-(2-phenylethyl) ethanediamide ##STR00567## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (1,2,3,4-tetrahydronaphthalen- 2-yl)ethanediamide ##STR00568## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- [2-(1-methylpyrrolidin-2- yl)ethyl]ethanediamide ##STR00569## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- [2-(phenyloxy) ethyl]ethanediamide ##STR00570## N'-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N- methyl-N-(2-phenylethyl) ethanediamide ##STR00571## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- {[3-(trifluoromethyl) phenyl]methyl}ethanediamide ##STR00572## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- {2-[3-(trifluoromethyl) phenyl]ethyl}ethanediamide ##STR00573## N-{3-fluoro-4-[(6- (methyloxy)-7-{[(1- methylpiperidin-4- yl)methyl]oxy}quinolin-4- yl)oxy]phenyl}-N'-(2- phenylethyl)ethanediamide ##STR00574## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- (1,2,3,4- tetrahydroisoquinolin-1- ylmethyl)ethanediamide ##STR00575## N-(4-{[6,7- bis(methyloxy)quinolin-4- yl]oxy}-3-fluorophenyl)-N'- [(2-methyl-1,2,3,4- tetrahydroisoquinolin-1- yl)methyl]ethanediamide ##STR00576## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- phenethyl-oxalamide ##STR00577## N-[4-(6,7-Dimethoxy- quinolin-4-yloxy)-3-fluoro- phenyl]-N'-(2-isopropyl- 1,2,3,4-tetrahydro- isoquinolin-1-ylmethyl)- oxalamide ##STR00578## N-[4-(6,7-Dimethoxy- quinolin-4-yloxy)-3-fluoro- phenyl]-N'-(2-ethyl-1,2,3,4- tetrahydro-isoquinolin-1- ylmethyl)-oxalamide ##STR00579## N-{4-[7-(3-Diethylamino- propoxy)-6-methoxy- quinolin-4-yloxy]-3-fluoro- phenyl}-N'-phenethyl- oxalamide ##STR00580## N-{3-Fluoro-4-[6-methoxy-7- (3-morpholin-4-yl-propoxy)- quinolin-4-yloxy]-phenyl}-N'- phenethyl-oxalamide ##STR00581## N-{3-Fluoro-4-[6-methoxy-7- (3-piperidin-1-yl-propoxy)- quinolin-4-yloxy]-phenyl}-N'- phenethyl-oxalamide ##STR00582## N-{4-[7-(2-Diethylamino- ethoxy)-6-methoxy-quinolin- 4-yloxy]-3-fluoro-phenyl}-N'- phenethyl-oxalamide ##STR00583## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-methyl-N'- phenethyl-oxalamide ##STR00584## 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 ##STR00585## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-2-(3-phenyl-pyrrolidin-1- yl)-acetamide ##STR00586## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-2-(2-phenyl-morpholin-4- yl)-acetamide ##STR00587## N-(2-Dimethylamino-2- phenyl-ethyl)-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00588## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-oxo-2-phenyl-ethyl)- oxalamide ##STR00589## N-Benzyl-N'-{3-fluoro-4-[6- methoxy-7-(1-methyl- piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00590## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(2-fluoro-phenyl)-ethyl]- oxalamide ##STR00591## N-[2-(3-Chloro-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00592## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(2-methoxy-phenyl)-ethyl]- oxalamide ##STR00593## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-pyridin-3-yl-ethyl)- oxalamide ##STR00594## N-Benzyl-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00595## N-[2-(2,5-Dimethoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-{piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00596## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(2-trifluoromethyl-phenyl)- ethyl]-oxalamide ##STR00597## N-[2-(2-Ethoxy-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00598## N-[2-(2,4-Dimethyl-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00599## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1S-phenyl-2-p-tolyl-ethyl)- oxalamide ##STR00600## N-[2-(4-Chloro-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00601## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamic acid ##STR00602## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(3-fluoro-phenyl)-ethyl]- oxalamide ##STR00603## N-[2-(2-Chloro-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00604## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(3-methoxy-phenyl)-ethyl]- oxalamide ##STR00605## N-(1,2-Diphenyl-ethyl)-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00606## N-[2-(2,4-Dichloro-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00607## N-[2-(3,4-Dimethoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00608## N-[2-(4-Ethyl-phenyl)-ethyl]- N'-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00609## N-[2-(4-Ethoxy-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00610## N-[2-(4-Ethoxy-3-methoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00611## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(4-phenoxy-phenyl)-ethyl]- oxalamide ##STR00612## N-[2-(3-Ethoxy-4-methoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00613## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-pyridin-2-yl-ethyl)- oxalamide ##STR00614## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-pyridin-4-yl-ethyl)- oxalamide ##STR00615## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(4-fluoro-phenyl)-ethyl]- oxalamide ##STR00616## N-[2-(2-Bromo-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00617## N-[2-(2-Chloro-6-fluoro- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00618## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2R-phenyl-propyl)-oxalamide ##STR00619## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- indan-1-yl-oxalamide ##STR00620## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-isobutyl- oxalamide ##STR00621## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-{3-methyl- butyl)-oxalamide ##STR00622## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-(2R- phenyl-propyl)-oxalamide ##STR00623## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-(2-phenyl- propyl)-oxalamide ##STR00624## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-indan-2-yl- oxalamide ##STR00625## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1R-phenyl-ethyl)-oxalamide ##STR00626## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1S-phenyl-ethyl)-oxalamide ##STR00627## N-[2-(3-Bromo-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00628## N-[2-(2,6-Dichloro-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00629## N-[2-(2,4-Dichloro-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00630## N-(2-Benzo[1,3]dioxol-5-yl- ethyl)-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00631## N-[2-(3-Bromo-4-methoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00632## N-[2-(3,5-Dimethoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00633## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-o-tolyl-ethyl)-oxalamide ##STR00634## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-m-tolyl-ethyl)-oxalamide ##STR00635## N-[2-(3-Ethoxy-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00636## N-[2-(3,4-Dimethyl-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00637## N-[2-(2,5-Dimethyl-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00638## N-[2-(3-Chloro-4-propoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00639## N-[2-(4-Butoxy-3-chloro- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00640## N-[2-(4-tert-Butyl-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00641## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(4-sulfamoyl-phenyl)- ethyl]-oxalamide ##STR00642## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(4-hydroxy-3-methoxy- phenyl)-ethyl]-oxalamide ##STR00643## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(3-hydroxy-4-methoxy- phenyl)-ethyl]-oxalamide ##STR00644## N-(2,4-Dichloro-benzyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00645## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (4-fluoro-2-trifluoromethyl- benzyl)-oxalamide ##STR00646## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1-p-tolyl-ethyl)-oxalamide ##STR00647## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (3-fluoro-4-trifluoromethyl- benzyl)-oxalamide ##STR00648## N-(3-Chloro-4-fluoro-benzyl)- N'-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00649## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [1-(3-methoxy-phenyl)-ethyl]- oxalamide ##STR00650## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1-naphthalen-2-yl-ethyl)- oxalamide ##STR00651## N-(4-Chloro-3- trifluoromethyl-benzyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00652## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1-p-tolyl-ethyl)-oxalamide ##STR00653## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (6-trifluoromethyl-pyridin-3- ylmethyl)-oxalamide ##STR00654## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-methyl-benzyl)-oxalamide ##STR00655## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (3-methyl-benzyl)-oxalamide ##STR00656## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (4-fluoro-3-trifluoromethyl- benzyl)-oxalamide ##STR00657## N-(3,5-Dichloro-benzyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00658## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1R,2,3,4-tetrahydro- naphthalen-1-yl)-oxalamide ##STR00659## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1S,2,3,4-tetrahydro- naphthalen-1-yl)-oxalamide ##STR00660## N-Cyclopentyl-N'-{3-fluoro- 4-[6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00661## N-[1-(4-Bromo-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00662## N-(2-Fluoro-benzyl)-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00663## N-[2-(3,4-Dichloro-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00664## N-(4-Fluoro-benzyl)-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00665## N-(2,3-Difluoro-benzyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00666## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-phenoxy-ethyl)-oxalamide ##STR00667## N-(2,2-Diphenyl-ethyl)-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00668## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [2-(4-methoxy-phenyl)-ethyl]- oxalamide ##STR00669## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-phenyl-propyl)-oxalamide ##STR00670## N-[2-(4-Bromo-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00671## 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 ##STR00672## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (3-fluoro-5-trifluoromethyl- benzyl)-oxalamide ##STR00673## N-(3,5-Difluoro-benzyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00674## N-(2-Chloro-5- trifluoromethyl-benzyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00675## N-[4-(6,7-Dimethoxy- quinolin-4-yloxy)-3-fluoro- phenyl]-N'-(2-dimethylamino- 2-phenyl-ethyl)-oxalamide ##STR00676## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (4-methoxy-benzyl)- oxalamide ##STR00677## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (4-trifluoromethyl-benzyl)- oxalamide ##STR00678## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (3-methoxy-benzyl)- oxalamide ##STR00679## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (3-trifluoromethyl-benzyl)- oxalamide ##STR00680## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (3-trifluoromethoxy-benzyl)- oxalamide ##STR00681## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-methoxy-benzyl)- oxalamide ##STR00682## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-trifluoromethyl-benzyl)- oxalamide ##STR00683## N-(3-Chloro-benzyl)-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00684## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-trifluoromethoxy-benzyl)- oxalamide ##STR00685## N-(2-Chloro-benzyl)-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00686## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (4-trifluoromethoxy-benzyl)- oxalamide ##STR00687## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-(4- methoxy-benzyl)-oxalamide ##STR00688## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-(4- trifluoromethyl-benzyl)- oxalamide ##STR00689## N-{4-[7-(Azetidin-3- ylmethoxy)-6-methoxy- quinolin-4-yloxy]-3-fluoro- phenyl}-N'-phenethyl- oxalamide ##STR00690## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-azetidin-3- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-phenethyl- oxalamide ##STR00691## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-hydroxy-2-phenyl-ethyl)- oxalamide ##STR00692## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1R-phenyl-propyl)- oxalamide ##STR00693## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (1R-phenyl-propyl)- oxalamide ##STR00694## N-(3,4-Difluoro-benzyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00695## N-(2,6-Difluoro-benzyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00696## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-[2-(4- fluoro-phenyl)-ethyl]- oxalamide ##STR00697## N-{3-Fluoro-4-[6-methoxy-7- (1-methyl-piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N'-phenyl- oxalamide ##STR00698## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (3-fluoro-phenyl)-oxalamide ##STR00699## N-(4-Chloro-3-fluoro- phenyl)-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00700## N-(3,4-Dimethoxy-phenyl)- N'-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00701## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (3-methyl-butyl)-oxalamide ##STR00702## N-(3,3-Dimethyl-butyl)-N'- {3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00703## N-(4-Chloro-benzyl)-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00704## N-(3,5-Dimethoxy-benzyl)- N'-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00705## N-(4-Butyl-benzyl)-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00706## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-p-tolyl-ethyl)-oxalamide ##STR00707## N-(3,5-Bis-trifluoromethyl- benzyl)-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00708## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- pyrazin-2-ylmethyl-oxalamide ##STR00709## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- pyridin-2-ylmethyl-oxalamide ##STR00710## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-fluoro-3-trifluoromethyl- benzyl)-oxalamide ##STR00711## N-[2-(2-Bromo-6-methoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00712## N-[2-(3,4-Dimethoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N-methyl- oxalamide ##STR00713## N-[2-(5-Bromo-2-methoxy- phenyl)-ethyl]-N'-{3-fluoro-4- [6-methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00714## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-fluoro-5-trifluoromethyl- benzyl)-oxalamide ##STR00715## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- [1-(4-fluoro-phenyl)-ethyl]- oxalamide ##STR00716## 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 ##STR00717## N-[2-(4-Amino-phenyl)- ethyl]-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00718## 2-(4-Benzyl-piperidin-1-yl)- N-{3-fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-acetamide ##STR00719## N-Ethyl-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00720## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- isopropyl-oxalamide ##STR00721## N-Butyl-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-oxalamide ##STR00722## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-methoxy-ethyl)-oxalamide ##STR00723## N-Cyclopropylmethyl-N'-{3- fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}- oxalamide ##STR00724## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-N'- (2-morpholin-4-yl-ethyl)- oxalamide ##STR00725## N-{3-Fluoro-4-[6-methoxy-7- (piperidin-4-ylmethoxy)- quinolin-4-yloxy]-phenyl}-2- oxo-2-pyrrolidin-1-yl- acetamide ##STR00726## N-Ethyl-N'-{3-fluoro-4-[6- methoxy-7-(piperidin-4- ylmethoxy)-quinolin-4- yloxy]-phenyl}-N-methyl- oxalamide ##STR00727## 11. A pharmaceutical composition comprising a compound according to claim 1 or 10, and a pharmaceutically acceptable carrier.