KIF18A inhibitors
Compounds of formula (I): as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.
1. A compound, selected from the group consisting of:
Ex. #
Chemical Structure
Name
1
N-(2-((1- Hydroxy- 2- methyl- propan- 2- yl)amino)- 6- methyl- pyrimidin- 4-yl)-4- (methyl- sulfonyl)- 2-(6- azaspiro [2.5]octan- 6-yl) benzamide
1-7
N-(2-((1- hydroxy- 2-methy- lpropan- 2-yl)amino)- 6-methyl- pyrimidin- 4- yl)-4-(N- (3-methyl- oxetan-3-yl) sulfamoyl)- 2-(6- azaspiro[2.5] octan-6- yl)benzamide
2-8
N-(2-(4,4- Difluoro- piperidin- 1-yl)-6- methyl- pyrimidin- 4-yl)-4-((1- methyl- cyclo- propane)- 1-sulfon- amido)- 2-(6- azaspiro [2.5] octan-6- yl)benzamide
3
(R)-4-((2- Hydroxy- ethyl) sulfon- amido)-N- (6- methyl-2- (2-methyl- morpholino) pyrimidin-4- yl)-2-(6- azaspiro[2.5] octan-6- yl)benzamide
4
N-(2-(4,4- Difluoro- piperidin- 1-yl)-6- methyl- pyrimidin- 4-yl)-4-((2- hydroxy- ethyl) sulfon- amido)- 2-(6- azaspiro [2.5] octan-6-yl) benzamide
5-1
(R)-N-(2- (4,4- Difluoro- piperidin- 1-yl)-6- methyl- pyrimidin- 4-yl)-4-((2- hydroxy-1- methyl- ethyl) sulfon- amido)- 2-(6- azaspiro [2.5] octan-6- yl)benzamide
5-2
(S)-N-(2- (4,4- Difluoro- piperidin-1- yl)-6- methyl- pyrimidin- 4-yl)-4-((2- hydroxy-1- methyl- ethyl) sulfon- amido)- 2-(6- azaspiro[2.5] octan-6-yl)- benzamide
6-35
N-(2-(4,4- Difluoro- piperidin- 1-yl)-6- methyl- pyrimidin- 4-yl)-4- (ethylsulfo- namido)- 2-(6- azaspiro [2.5] octan-6-yl) benzamide
7
N-(2-(3,3- Difluoro- azetidin- 1-yl)-6- methyl- pyrimidin- 4-yl)-4- ((2- hydroxy- ethyl) sulfon- amido)- 2-(6- azaspiro [2.5] octan-6-yl) benzamide
15
N-(2-(4,4- Difluoro- cyclohexyl)- 6-methyl- pyrimidin- 4-yl)-4-((2- hydroxy- ethyl) sulfon- amido)- 2-(6- azaspiro [2.5] octan-6-yl) benzamide
21
4-(Azetidin- 3- ylsulfonyl)- N-(2- (4,4-difluoro- piperidin- 1-yl)-6- methyl- pyrimidin- 4-yl)-2-(6- azaspiro [2.5] octan- 6-yl) benzamide;
or any pharmaceutically-acceptable salt thereof.
2. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
8. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
10. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
11. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , having the formula:
or the pharmaceutically acceptable salt thereof.
13. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
14. A pharmaceutical composition comprising an effective amount of the compound of claim 2 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
15. A pharmaceutical composition comprising an effective amount of the compound of claim 3 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
16. A pharmaceutical composition comprising an effective amount of the compound of claim 4 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
17. A pharmaceutical composition comprising an effective amount of the compound of claim 5 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
18. A pharmaceutical composition comprising an effective amount of the compound of claim 6 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
19. A pharmaceutical composition comprising an effective amount of the compound of claim 7 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
20. A pharmaceutical composition comprising an effective amount of the compound of claim 8 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
21. A pharmaceutical composition comprising an effective amount of the compound of claim 9 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
22. A pharmaceutical composition comprising an effective amount of the compound of claim 10 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
23. A pharmaceutical composition comprising an effective amount of the compound of claim 11 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
24. A pharmaceutical composition comprising an effective amount of the compound of claim 12 , or the pharmaceutically acceptable salt thereof, and a pharmaceutically-acceptable diluent or carrier.
25. A method of inhibiting KIF18A in a cell, comprising contacting the cell with the compound of claim 1 , or the pharmaceutically acceptable salt thereof, or the composition according to claim 13 .