Uracil derivatives as AXL and c-MET kinase inhibitors
The present application provides compounds of Formula I or salt forms thereof, wherein R a , R b , R c , R d , D, W, R 1a , R 1b , R 1c , Y, R 3 , X, E and G are as defined herein, compositions, methods of treatment and uses thereof.
1. A compound which is 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 having the structure
or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising a compound which is 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 having the structure
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
3. The pharmaceutical composition according to claim 2 , wherein the composition comprises from about 0.1 mg to about 1,000 mg of 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, or a pharmaceutically acceptable salt thereof.
4. The pharmaceutical composition according to claim 3 , wherein the composition comprises from about 1 mg to about 1,000 mg of 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, or a pharmaceutically acceptable salt thereof.
5. The pharmaceutical composition according to claim 4 , wherein the composition comprises from about 1 mg to about 500 mg of 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, or a pharmaceutically acceptable salt thereof.
6. The pharmaceutical composition according to claim 5 , wherein the composition comprises from about 1 mg to about 100 mg of 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, or a pharmaceutically acceptable salt thereof.
7. The pharmaceutical composition according to claim 2 , wherein the composition comprises from about 1% to about 95% (w/w) of 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, or a pharmaceutically acceptable salt thereof.
8. The pharmaceutical composition according to claim 7 , wherein the composition comprises from about 10% to about 80% (w/w) of 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, or a pharmaceutically acceptable salt thereof.
9. The pharmaceutical composition according to claim 8 , wherein the composition comprises from about 20% to about 70% (w/w) of 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, or a pharmaceutically acceptable salt thereof.
10. The pharmaceutical composition according to claim 9 , wherein the composition comprises from about 30% to about 60% (w/w) of 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, or a pharmaceutically acceptable salt thereof.
11. The pharmaceutical composition according to claim 10 , wherein the composition comprises from about 40% to about 50% (w/w) of 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, or a pharmaceutically acceptable salt thereof.