Inhibtors of RAF kinases
Provided herein are inhibitors of receptor tyrosine kinase effector, RAF, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
1. A compound, or pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of:
N-(3-[2-[(3R)-3-hydroxybut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-(3-[2-[(3S)-3-hydroxybut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-[3-[2-(3-hydroxy-3-methylbut-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-2-(trifluoromethyl)pyridine-4-carboxamide;
N-[3-[2-(3-hydroxyprop-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-2-(trifluoromethyl)pyridine-4-carboxamide;
(3S)—N-[3-[2-(2-aminopyrimidin-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;
N-(3-{2-[(3S)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-(3-{2-[(3R)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-(3-{2-[3-(dimethylamino)prop-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-{4-methyl-3-[2-(morpholin-4-yl)-6-[3-(pyrrolidin-1-yl)prop-1-yn-1-yl]pyridin-4-yl]phenyl}-2-(trifluoromethyl)pyridine-4-carboxamide;
N-(4-methyl-3-{2-[3-(methylamino)prop-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}phenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-(3-{2-[(3S)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-(4-methyl-3-{2-[(3R)-3-(methylamino)but-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}phenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-[3-[2-(3-hydroxyprop-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-2-(trifluoromethyl)pyridine-4-carboxamide;
N-(3-{2-[(3S)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide;
N-{4-methyl-3-[2-(morpholin-4-yl)-6-[(3S)-4,4,4-trifluoro-3-hydroxybut-1-yn-1-yl)pyridin-4-yl]phenyl}-2-(trifluoromethyl)pyridine-4-carboxamide;
N-{4-methyl-3-[2-(morpholin-4-yl)-6-[(3R)-4,4,4-trifluoro-3-hydroxybut-1-yn-1-yl]pyridin-4-yl]phenyl}-2-(trifluoromethyl)pyridine-4-carboxamide;
N-{3-[2-(3-amino-3-methylbut-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl}-2-(trifluoromethyl)pyridine-4-carboxamide; and
N-(3-{2-[(3S)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide.
2. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: N-[3-[2-(3-hydroxy-3-methylbut-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-2-(trifluoromethyl)pyridine-4-carboxamide.
3. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: N-{3-[2-(3-amino-3-methylbut-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl}-2-(trifluoromethyl)pyridine-4-carboxamide.
4. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: N-(3-{2-[(3S)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide.
5. The compound, or pharmaceutically acceptable salt or solvate thereof, of claim 1 having the structure of: N-(3-{2-[(3S)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide.
6. A pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in claim 1 and a pharmaceutically acceptable excipient.
7. The pharmaceutical composition of claim 6 , wherein the compound is N-[3-[2-(3-hydroxy-3-methylbut-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-2-(trifluoromethyl)pyridine-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof.
8. The pharmaceutical composition of claim 6 , wherein the compound is N-{3-[2-(3-amino-3-methylbut-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl}-2-(trifluoromethyl)pyridine-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof.
9. The pharmaceutical composition of claim 6 , wherein the compound is N-(3-{2-[(3S)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof.
10. The pharmaceutical composition of claim 6 , wherein the compound is N-(3-{2-[(3S)-3-aminobut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-2-(trifluoromethyl)pyridine-4-carboxamide, or pharmaceutically acceptable salt or solvate thereof.