US 2014/0275077 A1Published application

Uracil derivatives as axl and c-met kinase inhibitors

AssigneeCephalon, Inc.

InventorsReddeppa Reddy Dandu, Robert L. Hudkins, Kurt A. Josef, Catherine P. Prouty, Rabindranath Tripathy

Life of this patent

Estimating the term…

Abstract

The present application provides compounds of Formula I or salt forms thereof, wherein Ra, Rb, Rc, Rd, D, W, R1a, R1b, R1c, Y, R3, X, E and G are as defined herein, compositions, methods of treatment and uses thereof.

Claims21

Dependent claims

A compound of Formula I or a salt form thereof,

wherein:
E and G are independently chosen from H, C1-6alkyl optionally substituted by 1-6 R19, C2-6alkenyl optionally substituted by 1-6 R19, C2-6alkynyl optionally substituted by 1-6 R19, C6-11aryl optionally substituted by 1-6 R19, C3-11cycloalkyl optionally substituted by 1-6 R19, 3-15 membered heterocyclyl optionally substituted by 1-6 R19, 5-15 membered heteroaryl optionally substituted by 1-6 R19, —C(═O)R20, —C(═O)OR20, —C(═O)NR22R23, —S(═O)2R20, and —S(═O)2NR22R23;
X is N or C—R4;
Y is N or C—R1d;
R3 is H or C1-6alkyl;
D is —O—, —S—, —SO—, —SO2—, —C(═O)—, —CHOH—, —CH2—, —NH— or —NC1-6alkyl-;
W is CH or N;
Ra, Rb, Rc, Rd, R1a, R1b, R1c, R1d, and R4 are independently chosen from H, C1-6alkyl optionally substituted by 1-6 R119, C2-6alkenyl optionally substituted by 1-6 R119, C2-6alkynyl optionally substituted by 1-6 R119, C6-11aryl optionally substituted by 1-6 R119, C3-11 cycloalkyl optionally substituted by 1-6 R119, 3-15 membered heterocyclyl optionally substituted by 1-6 R119, 5-15 membered heteroaryl optionally substituted by 1-6 R119, halogen, —CN, —C(═O)R110, —C(═O)OR110, —C(═O)NR112R113, —NC, —NO2, —NR112R113, NR114C(═O)R110, —NR114C(═O)OR11, NR114C(═O)NR112R113, NR114S(═O)2R111, —NR114S(═O)2NR112R113, —OR110, —OCN, —OC(═O)R110, —OC(═O)NR112R113, —OC(═O)OR110, —S(═O)nR110, and —S(═O)2NR112R113;
or any of Ra and Rb, Ra and Rd, and Rb and Rc can, together with the atoms linking them, form a C6-11aryl optionally substituted by 1-6 R119, C3-11cycloalkyl optionally substituted by 1-6 R119, 3-15 membered heterocyclyl optionally substituted by 1-6 R119 or a 5-15 membered heteroaryl optionally substituted by 1-6 R119;
R19 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R39, C2-6alkenyl optionally substituted by 1-6 R39, C2-6alkynyl optionally substituted by 1-6 R39, C6-11aryl optionally substituted by 1-6 R39, C3-11cycloalkyl optionally substituted by 1-6 R39, 3-15 membered heterocyclyl optionally substituted by 1-6 R39, 5-15 membered heteroaryl optionally substituted by 1-6 R39, halogen, —CN, —C(═O)R30, —C(═O)OR30, —C(═O)NR32R33, —NO2, —NR32R33, —NR34C(═O)R30, —NR34C(═O)OR31, —NR34C(═O)NR32R33, NR34S(═O)2R31, NR34S(═O)2NR32R33, —OR30, ═O, —OC(═O)R30, —OC(═O)NR32R33, —OC(═O)OR30, —S(═O)nR30, and —S(═O)2NR32R33;
R20, R30, R31, and R34 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R49, C2-6alkenyl optionally substituted by 1-6 R49, C2-6alkynyl optionally substituted by 1-6 R49, C6-11aryl optionally substituted by 1-6 R49, C3-11cycloalkyl optionally substituted by 1-6 R49, 3-15 membered heterocyclyl optionally substituted by 1-6 R49, and 5-15 membered heteroaryl optionally substituted by 1-6 R49;
R22, R23, R32 and R33 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R59, C2-6alkenyl optionally substituted by 1-6 R59C2-6alkynyl optionally substituted by 1-6 R59, C6-11aryl optionally substituted by 1-6 R59, C3-11cycloalkyl optionally substituted by 1-6 R59, 3-15 membered heterocyclyl optionally substituted by 1-6 R59, and 5-15 membered heteroaryl optionally substituted by 1-6 R59;
or any R22 and R23 and/or R32 and R33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocyclyl optionally substituted by 1-6 R69 or a 5-15 membered heteroaryl optionally substituted by 1-6 R69;
R39, R49, R59 and R69 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R79, C2-6alkenyl optionally substituted by 1-6 R79, C2-6alkynyl optionally substituted by 1-6 R79, C6-11aryl optionally substituted by 1-6 R79, C3-11cycloalkyl optionally substituted by 1-6 R79, 3-15 membered heterocyclyl optionally substituted by 1-6 R79, 5-15 membered heteroaryl optionally substituted by 1-6 R79, halogen, —CN, —C(═O)R70, —C(═O)OR70, —C(═O)NR72R73, —NO2, —NR72R73, —NR74C(═O)R70, —NR74C(═O)OR71, —NR74C(═O)NR72R73, —NR74S(═O)2R71, —NR74S(═O)2NR72R73, —OR70, ═O, —OC(═O)R70, —OC(═O)NR72R73, —S(═O)nR70, and —S(═O)2NR72R73;
R70, R71, R72, R73, and R74 at each occurrence is independently chosen from H, C1-6alkyl and C1-6-haloalkyl;
R79 at each occurrence is independently chosen from C1-6alkyl, C1-6-haloalkyl, benzyl, halogen, —CN, —C(═O)(C1-6alkyl), —C(═O)O(C1-6alkyl), —C(═O)N(C1-6alkyl)2, —C(═O)OH, —C(═O)NH2, —C(═O)NHC1-6alkyl, —NO2, —NH2, —NHC1-6alkyl, —N(C1-6alkyl)2, —NHC(═O)C1-6alkyl, —NHS(═O)2C1-6alkyl, —OH, —OC1-6alkyl, ═O, —OC(═O)C1-6alkyl, —OS(═O)2C1-6alkyl, —S(═O)2C1-6alkyl, and —S(═O)2N(C1-6alkyl)2;
R110, R111, and R114 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R129, C2-6alkenyl optionally substituted by 1-6 R129, C2-6alkynyl optionally substituted by 1-6 R129, C6-11aryl optionally substituted by 1-6 R129, C3-11 cycloalkyl optionally substituted by 1-6 R129, 3-15 membered heterocyclyl optionally substituted by 1-6 R129, and 5-15 membered heteroaryl optionally substituted by 1-6 R129;
R112 and R113 at each occurrence is independently chosen from H, C1-6 alkyl optionally substituted by 1-6 R139, C2-6alkenyl optionally substituted by 1-6 R139, C2-6alkynyl optionally substituted by 1-6 R139, C6-11aryl optionally substituted by 1-6 R139, C3-11cycloalkyl optionally substituted by 1-6 R139, 3-15 membered heterocyclyl optionally substituted by 1-6 R139, and 5-15 membered heteroaryl optionally substituted by 1-6 R139;
or any R112 and R113 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocyclyl optionally substituted by 1-6 R149or a 5-15 membered heteroaryl optionally substituted by 1-6 R149;
R119 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R159, C2-6alkenyl optionally substituted by 1-6 R159, C2-6alkynyl optionally substituted by 1-6 R159, C6-11aryl optionally substituted by 1-6 R159, C3-11cycloalkyl optionally substituted by 1-6 R159, 3-15 membered heterocyclyl optionally substituted by 1-6 R159, 5-15 membered heteroaryl optionally substituted by 1-6 R159, halogen, —CN, —C(═O)R150, —C(═O)OR150, —C(═O)NR152R153, —NC, —NO2, —NR152R153, NR154C(═O)R150, —NR154C(═O)OR, —NR154C(═O)NR152R153, —NR154S(═O)2R151, —NR154S(═O)2NR152R153, —OR150, ═O, —OC(═O)R150, —OC(═O)NR152R153, —S(═O)R150, and —S(═O)2NR152R153;
R150, R151, R152, R153 and R154 at each occurrence is independently chosen from H, C1-6alkyl, benzyl, and C1-6-haloalkyl;
R129, R139, R149, and R159 at each occurrence is independently chosen from C1-6alkyl, C1-6-haloalkyl, benzyl, halogen, —CN, —C(═O)(C1-6alkyl), —C(═O)O(C1-6alkyl), —C(═O)N(C1-6alkyl)2, —C(═O)OH, —C(═O)NH2, —C(═O)NHC1-6alkyl, —NO2, —NH2, —NHC1-6alkyl, —N(C1-6alkyl)2, —NHC(═O)C1-6alkyl, —NHS(═O)2C1-6alkyl, —OH, —OC1-6alkyl, ═O, —OC(═O)C1-6alkyl, —OS(═O)2C1-6alkyl, —S(═O)2C1-6alkyl, and —S(═O)2N(C1-6alkyl)2;
and
n at each occurrence is independently chosen from 0, 1, and 2.

21 more elements

A compound that is chosen from:

1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylicacid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]amide;
3-(4-Fluorophenyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluorophenyl)-1-(2-methoxyethyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-(2-Ethoxyethyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-Cyclopropylmethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-(3-methoxypropyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-isobutyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-Allyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-(2-Benzyloxyethyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-2,4-dioxo-1-propyl-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-(2-isopropoxyethyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-(3-Benzyloxypropyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro phenyl]-amide;
1-(3,3-Difluoro-allyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-(3-methyl-but-2-enyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-(2-morpholin-4-yl-ethyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro phenyl]-amide;
3-(4-Fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-amide;
1-(2-Benzyloxyethyl)-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-amide;
1-(2-Dimethylaminoethyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-(3-Benzyloxypropyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-amide;
1-(3-Benzyloxypropyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-2-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-amide;
3-(4-Fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-amide;
3-Cyclohexyl-1-ethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-2,4-dioxo-1-(2-pyrrolidin-1-yl-ethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro phenyl]-amide;
3-(4-Fluorophenyl)-2,4-dioxo-1-(2-piperidin-1-yl-ethyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-phenyl]-amide;
1-Cyclobutyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-2,4-dioxo-1-(tetrahydropyran-4-yl)-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro phenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [5-(6,7-dimethoxyquinolin-4-yloxy)-pyridin-2-yl]-amide was synthesized starting with 5-(6,7-dimethoxyquinolin-4-yloxy)-pyridin-2-ylamine;
1-Ethyl-3-(4-fluorophenyl)-6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-diethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [5-(6,7-dimethoxyquinolin-4-yloxy)-pyridin-2-yl]-amide;
1-Cyclopropylmethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [5-(6,7-dimethoxyquinolin-4-yloxy)pyridin-2-yl]-amide;
3-(4-Fluorophenyl)-2,4-dioxo-1-pentyl-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-diethoxyquinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(5,7-dimethoxyquinolin-4-yloxy)phenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(5,7-dimethoxyquinolin-4-yloxy)-phenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(7-benzyloxy-6-methoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(7-benzyloxy-6-methoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxyquinolin-4-yloxy)phenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid {3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)quinolin-4-yloxy]phenyl}-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid {3-fluoro-4-[6-methoxy-7-(2-methoxyethoxy)quinolin-4-yloxy]-phenyl}-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid {3-fluoro-4-[6-methoxy-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-yloxy]phenyl}-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [3-fluoro-4-(7-hydroxy-6-methoxyquinolin-4-yloxy)-phenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid {3-fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]phenyl}-amide;
3-(4-Fluorophenyl)-1-(2-hydroxyethyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-(3-hydroxypropyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-(3-hydroxypropyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluoro-phenyl]-amide;
3-(4-Fluorophenyl)-1-(3-hydroxypropyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-amide;
3-(4-Fluorophenyl)-1-(2-hydroxyethyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)phenyl]-amide;
1-((S)-2,3-Dihydroxypropyl)-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-(4-hydroxybutyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6-cyano-7-methoxy-quinolin-4-yloxy)-phenyl]-amide;
3-(4-fluoro-phenyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid {4-[(6,7-dimethoxy-quinolin-4-yl)-hydroxy-methyl]-3-fluoro-phenyl}-amide;
3-(4-fluoro-phenyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-ylmethyl)-3-fluoro-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [3-cyclopropyl-4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [3-cyclopropyl-4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-prop-2-ynyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-(2-imidazol-1-yl-ethyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-(2-pyrazol-1-yl-ethyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-phenethyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-[2-(1,3-Dioxolan-2-yl-ethyl)]-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-Diethylcarbamoylmethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-(2-morpholin-4-yl-2-oxo-ethyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-[2-(2-oxo-pyrrolidin-1-yl)-ethyl]-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-(2-Fluoro-ethyl)-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
[5-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-3-fluoro-phenylcarbamoyl]-3-(4-fluoro-phenyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetic acid tert-butyl ester;
[5-[4-(6,7-Dimethoxyquinolin-4-yloxy)-3-fluorophenylcarbamoyl]-3-(4-fluorophenyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-acetic acid;
3-(4-Fluoro-phenyl)-1-oxazol-2-ylmethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-(tetrahydro-furan-2-ylmethyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-(tetrahydro-pyran-4-ylmethyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-(2-methyl-thiazol-4-ylmethyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-Cyclopentyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-Benzyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-[2-(2-fluoro-phenyl)-ethyl]-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-[2-(4-fluoro-phenyl)-ethyl]-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-(2-Cyclohexyl-ethyl)-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-(3-phenyl-propyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-(2-oxo-2-pyrrolidin-1-yl-ethyl)-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-Dimethylcarbamoylmethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]-amide;
1-(1-Dimethylcarbamoyl-2-oxo-propyl)-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluoro-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluoro-phenyl]-amide;
1-Allyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3,5-difluoro-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3,5-difluoro-phenyl]-amide;
3-Ethyl-1-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1,3-Dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]-amide;
1,3-Diethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1,3-Diisopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1,3-Bis-cyclopropylmethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1,3-Diallyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1,3-Bis-(3-methyl-but-2-enyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
2,4-Dioxo-1,3-di-prop-2-ynyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
2,4-Dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-Ethyl-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-Isopropyl-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1-propyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinoline-4-carbonyl)-3-fluoro-phenyl]-amide;
4-(4-Fluoro-phenyl)-2-isopropyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-(4-Fluorophenyl)-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
2-Ethyl-4-(4-fluoro-phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-(4-Fluorophenyl)-2-isopropyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-9-yloxy)-3-fluorophenyl]-amide;
4-(4-Fluoro-phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-(4-Fluorophenyl)-2-(2-hydroxyethyl)-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
2-Ethyl-4-(4-fluorophenyl)-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carboxylic acid [4-(6,7-diethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-(4-Fluoro-phenyl)-2-isopropyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [5-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-2-yl]-amide;
4-(4-Fluorophenyl)-2-isopropyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [3-fluoro-4-(7-methoxyquinolin-4-yloxy)-phenyl]-amide;
4-(4-Fluorophenyl)-3,5-dioxo-2-(2-oxo-propyl)-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
4-(4-Fluoro-phenyl)-3,5-dioxo-2-prop-2-ynyl-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
2-Methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
2-Methyl-3,5-dioxo-4-prop-2-ynyl-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-uinolin-4-yloxy)-3-fluoro-phenyl]-amide;
2-Methyl-4-(5-methyl-isoxazol-3-ylmethyl)-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
2-Methyl-3,5-dioxo-4-pent-2-ynyl-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-uinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-(4-Hydroxy-but-2-ynyl)-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-(1,5-Dimethyl-1H-pyrazol-3-ylmethyl)-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
2-Methyl-3,5-dioxo-4-(2-pyrazol-1-yl-ethyl)-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
2-Methyl-4-(1-methyl-1H-[1,2,4]triazol-3-ylmethyl)-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-Cyanomethyl-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-Ethyl-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-Allyl-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-Cyclopropylmethyl-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
2-Methyl-3,5-dioxo-4-(tetrahydro-pyran-4-ylmethyl)-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-Isobutyl-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-Cyclobutylmethyl-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
4-(2,2-Dimethylpropyl)-2-methyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluorophenyl]-amide;
±2-Methyl-4-(2-methyl-butyl)-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-([1,3]dioxolo[4,5-g]quinolin-8-yloxy)-3-fluoro-phenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-9-yloxy)-3-fluoro-phenyl]-amide;
2-Cyclopropylmethyl-4-(4-fluorophenyl)-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-ylamino)-phenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxyquinolin-4-ylamino)-phenyl]-amide;
4-(4-Fluoro-phenyl)-2-isopropyl-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-ylamino)-phenyl]-amide;
1-ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-ylsulfanyl)-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-ylsulfanyl)-phenyl]-amide;
3-(4-Fluorophenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid {4-[(6,7-dimethoxy-quinolin-4-yl)-methyl-amino]-phenyl}-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid {4-[(6,7-dimethoxy-quinolin-4-yl)-methylamino]-phenyl}-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinazolin-4-yloxy)-phenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinazolin-4-yloxy)-phenyl]-amide;
1-Ethyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-methoxyphenyl]-amide;
1-Methyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-methoxy-phenyl]-amide;
1-Isopropyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-methoxy-phenyl]-amide;
1-Methyl-3-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2,3-difluoro-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2,3-difluoro-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-methyl-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-methyl-phenyl]-amide;
3-(4-Fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-methoxy-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-methoxy-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [3-chloro-4-(6,7-dimethoxy-quinolin-4-yloxy)-3-methoxy-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-dimethylamino-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-dimethylamino-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-isopropyl-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-isopropyl-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2,3-dimethyl-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2,3-dimethyl-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-trifluoromethyl-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-trifluoromethyl-phenyl]-amide;
1-Ethyl-3-(4-fluoro-phenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3,5-dimethyl-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3,5-dimethyl-phenyl]-amide;
3-(4-Fluoro-phenyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-methyl-phenyl]-amide;
2-Ethyl-4-(4-fluoro-phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxylic acid [5-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-2-yl]-amide;
2-Ethyl-4-(4-fluoro-phenyl)-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-3-isopropyl-phenyl]-amide;
or
4-(4-Fluoro-phenyl)-2-isopropyl-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-2-methoxy-phenyl]-amide;
or
a pharmaceutically acceptable salt thereof.

165 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/276,138Filed 13 May 2014
Priority: 14 Nov 2011
Published: 18 Sep 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61K 31/4725
Non-condensed isoquinolines, e.g. papaverine: containing further heterocyclic rings
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/513
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine

Family

Application61/559,312Us provisional application · filed 14 Nov 2011
Application14/276,138Continuation
US 9,029,538 B2Related patent
US 2014/0275077 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula I or a salt form thereof,

wherein:
E and G are independently chosen from H, C1-6alkyl optionally substituted by 1-6 R19, C2-6alkenyl optionally substituted by 1-6 R19, C2-6alkynyl optionally substituted by 1-6 R19, C6-11aryl optionally substituted by 1-6 R19, C3-11cycloalkyl optionally substituted by 1-6 R19, 3-15 membered heterocyclyl optionally substituted by 1-6 R19, 5-15 membered heteroaryl optionally substituted by 1-6 R19, —C(═O)R20, —C(═O)OR20, —C(═O)NR22R23, —S(═O)2R20, and —S(═O)2NR22R23;
X is N or C—R4;
Y is N or C—R1d;
R3 is H or C1-6alkyl;
D is —O—, —S—, —SO—, —SO2—, —C(═O)—, —CHOH—, —CH2—, —NH— or —NC1-6alkyl-;
W is CH or N;
Ra, Rb, Rc, Rd, R1a, R1b, R1c, R1d, and R4 are independently chosen from H, C1-6alkyl optionally substituted by 1-6 R119, C2-6alkenyl optionally substituted by 1-6 R119, C2-6alkynyl optionally substituted by 1-6 R119, C6-11aryl optionally substituted by 1-6 R119, C3-11 cycloalkyl optionally substituted by 1-6 R119, 3-15 membered heterocyclyl optionally substituted by 1-6 R119, 5-15 membered heteroaryl optionally substituted by 1-6 R119, halogen, —CN, —C(═O)R110, —C(═O)OR110, —C(═O)NR112R113, —NC, —NO2, —NR112R113, NR114C(═O)R110, —NR114C(═O)OR11, NR114C(═O)NR112R113, NR114S(═O)2R111, —NR114S(═O)2NR112R113, —OR110, —OCN, —OC(═O)R110, —OC(═O)NR112R113, —OC(═O)OR110, —S(═O)nR110, and —S(═O)2NR112R113;
or any of Ra and Rb, Ra and Rd, and Rb and Rc can, together with the atoms linking them, form a C6-11aryl optionally substituted by 1-6 R119, C3-11cycloalkyl optionally substituted by 1-6 R119, 3-15 membered heterocyclyl optionally substituted by 1-6 R119 or a 5-15 membered heteroaryl optionally substituted by 1-6 R119;
R19 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R39, C2-6alkenyl optionally substituted by 1-6 R39, C2-6alkynyl optionally substituted by 1-6 R39, C6-11aryl optionally substituted by 1-6 R39, C3-11cycloalkyl optionally substituted by 1-6 R39, 3-15 membered heterocyclyl optionally substituted by 1-6 R39, 5-15 membered heteroaryl optionally substituted by 1-6 R39, halogen, —CN, —C(═O)R30, —C(═O)OR30, —C(═O)NR32R33, —NO2, —NR32R33, —NR34C(═O)R30, —NR34C(═O)OR31, —NR34C(═O)NR32R33, NR34S(═O)2R31, NR34S(═O)2NR32R33, —OR30, ═O, —OC(═O)R30, —OC(═O)NR32R33, —OC(═O)OR30, —S(═O)nR30, and —S(═O)2NR32R33;
R20, R30, R31, and R34 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R49, C2-6alkenyl optionally substituted by 1-6 R49, C2-6alkynyl optionally substituted by 1-6 R49, C6-11aryl optionally substituted by 1-6 R49, C3-11cycloalkyl optionally substituted by 1-6 R49, 3-15 membered heterocyclyl optionally substituted by 1-6 R49, and 5-15 membered heteroaryl optionally substituted by 1-6 R49;
R22, R23, R32 and R33 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R59, C2-6alkenyl optionally substituted by 1-6 R59C2-6alkynyl optionally substituted by 1-6 R59, C6-11aryl optionally substituted by 1-6 R59, C3-11cycloalkyl optionally substituted by 1-6 R59, 3-15 membered heterocyclyl optionally substituted by 1-6 R59, and 5-15 membered heteroaryl optionally substituted by 1-6 R59;
or any R22 and R23 and/or R32 and R33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocyclyl optionally substituted by 1-6 R69 or a 5-15 membered heteroaryl optionally substituted by 1-6 R69;
R39, R49, R59 and R69 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R79, C2-6alkenyl optionally substituted by 1-6 R79, C2-6alkynyl optionally substituted by 1-6 R79, C6-11aryl optionally substituted by 1-6 R79, C3-11cycloalkyl optionally substituted by 1-6 R79, 3-15 membered heterocyclyl optionally substituted by 1-6 R79, 5-15 membered heteroaryl optionally substituted by 1-6 R79, halogen, —CN, —C(═O)R70, —C(═O)OR70, —C(═O)NR72R73, —NO2, —NR72R73, —NR74C(═O)R70, —NR74C(═O)OR71, —NR74C(═O)NR72R73, —NR74S(═O)2R71, —NR74S(═O)2NR72R73, —OR70, ═O, —OC(═O)R70, —OC(═O)NR72R73, —S(═O)nR70, and —S(═O)2NR72R73;
R70, R71, R72, R73, and R74 at each occurrence is independently chosen from H, C1-6alkyl and C1-6-haloalkyl;
R79 at each occurrence is independently chosen from C1-6alkyl, C1-6-haloalkyl, benzyl, halogen, —CN, —C(═O)(C1-6alkyl), —C(═O)O(C1-6alkyl), —C(═O)N(C1-6alkyl)2, —C(═O)OH, —C(═O)NH2, —C(═O)NHC1-6alkyl, —NO2, —NH2, —NHC1-6alkyl, —N(C1-6alkyl)2, —NHC(═O)C1-6alkyl, —NHS(═O)2C1-6alkyl, —OH, —OC1-6alkyl, ═O, —OC(═O)C1-6alkyl, —OS(═O)2C1-6alkyl, —S(═O)2C1-6alkyl, and —S(═O)2N(C1-6alkyl)2;
R110, R111, and R114 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R129, C2-6alkenyl optionally substituted by 1-6 R129, C2-6alkynyl optionally substituted by 1-6 R129, C6-11aryl optionally substituted by 1-6 R129, C3-11 cycloalkyl optionally substituted by 1-6 R129, 3-15 membered heterocyclyl optionally substituted by 1-6 R129, and 5-15 membered heteroaryl optionally substituted by 1-6 R129;
R112 and R113 at each occurrence is independently chosen from H, C1-6 alkyl optionally substituted by 1-6 R139, C2-6alkenyl optionally substituted by 1-6 R139, C2-6alkynyl optionally substituted by 1-6 R139, C6-11aryl optionally substituted by 1-6 R139, C3-11cycloalkyl optionally substituted by 1-6 R139, 3-15 membered heterocyclyl optionally substituted by 1-6 R139, and 5-15 membered heteroaryl optionally substituted by 1-6 R139;
or any R112 and R113 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocyclyl optionally substituted by 1-6 R149or a 5-15 membered heteroaryl optionally substituted by 1-6 R149;
R119 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R159, C2-6alkenyl optionally substituted by 1-6 R159, C2-6alkynyl optionally substituted by 1-6 R159, C6-11aryl optionally substituted by 1-6 R159, C3-11cycloalkyl optionally substituted by 1-6 R159, 3-15 membered heterocyclyl optionally substituted by 1-6 R159, 5-15 membered heteroaryl optionally substituted by 1-6 R159, halogen, —CN, —C(═O)R150, —C(═O)OR150, —C(═O)NR152R153, —NC, —NO2, —NR152R153, NR154C(═O)R150, —NR154C(═O)OR, —NR154C(═O)NR152R153, —NR154S(═O)2R151, —NR154S(═O)2NR152R153, —OR150, ═O, —OC(═O)R150, —OC(═O)NR152R153, —S(═O)R150, and —S(═O)2NR152R153;
R150, R151, R152, R153 and R154 at each occurrence is independently chosen from H, C1-6alkyl, benzyl, and C1-6-haloalkyl;
R129, R139, R149, and R159 at each occurrence is independently chosen from C1-6alkyl, C1-6-haloalkyl, benzyl, halogen, —CN, —C(═O)(C1-6alkyl), —C(═O)O(C1-6alkyl), —C(═O)N(C1-6alkyl)2, —C(═O)OH, —C(═O)NH2, —C(═O)NHC1-6alkyl, —NO2, —NH2, —NHC1-6alkyl, —N(C1-6alkyl)2, —NHC(═O)C1-6alkyl, —NHS(═O)2C1-6alkyl, —OH, —OC1-6alkyl, ═O, —OC(═O)C1-6alkyl, —OS(═O)2C1-6alkyl, —S(═O)2C1-6alkyl, and —S(═O)2N(C1-6alkyl)2;
and
n at each occurrence is independently chosen from 0, 1, and 2.

21 more elements

Facts

Application

14/276,138Filed 13 May 2014

Priority

14 Nov 2011

Published

18 Sep 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61K 31/4725
Non-condensed isoquinolines, e.g. papaverine: containing further heterocyclic rings
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/513
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine