Spirocyclic compounds
Disclosed herein are spirocyclic compounds, together with pharmaceutical compositions and methods of ameliorating and/or treating a cancer described herein with one or more of the compounds described herein.
1. A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from the group consisting of C 3-4 cycloalkyl, halophenyl, C 1-4 alkoxyphenyl, C 1-4 alkoxyhalophenyl, C 1-4 dialkoxyphenyl, halopyridinyl, C 1-4 alkoxypyridinyl, C 1-4 alkylpyridinyl, C 3-5 cycloalkoxypyridinyl, methylbenzoxazolyl and tetrahydropyranyl;
R 2 and R 3 are each independently methyl, hydrogen or deuterium;
Y 1 and Y 2 are each independently CH or N;
Y 3 is C, CH or N; and
Y 9 and Y 10 are each independently CH or N;
Z 1 is C 1-3 alkyl optionally substituted with hydroxy;
wherein is a single bond when Y 3 is N or CH and is a double bond when Y 3 is C; and
wherein the compound of Formula (I) is not
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, of the Formula (IA):
wherein:
R 1 is selected from the group consisting of halophenyl, halopyridinyl, C 1-4 alkoxypyridinyl, C 1-4 alkylpyridinyl, methylbenzoxazolyl and tetrahydropyranyl; and
R 2 and R 3 are each independently hydrogen or deuterium.
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is halophenyl or halopyridinyl.
4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 1 is fluorophenyl or fluoropyridinyl.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-4 alkoxypyridinyl or C 1-4 alkylpyridinyl.
6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 1 is isopropoxypyridinyl, methoxypyridinyl or methylpyridinyl.
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methylbenzoxazolyl or tetrahydropyranyl.
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of C 3-4 cycloalkyl, C 1-4 alkoxyphenyl, C 1-4 alkoxyhalophenyl, C 1-4 dialkoxyphenyl, and C 3-5 cycloalkoxypyridinyl.
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein is a double bond.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein is a single bond.
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 1 is CH.
12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 1 is N.
13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 2 is CH.
14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 2 is N.
15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 3 is C.
16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 3 is CH.
17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 3 is N.
18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 9 is N or CH.
19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y 10 is N or CH.
20. The compound of claim 1 , selected from the group consisting of
or a pharmaceutically acceptable salt of the foregoing.
21. The compound of claim 2 , selected from the group consisting of
or a pharmaceutically acceptable salt of the foregoing.
22. The compound of claim 1 , selected from the group consisting of
(S)-7-(2-(4-(5-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)thiazol-2-yl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-2-(3-(6-isopropoxypyridin-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2,7-diazaspiro[4.4]nonan-1-one;
(S)-7-(2-(4-(5-(1-methyl-1H-1,2,4-triazol-3-yl)thiazol-2-yl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-2-(3-(2-methylbenzo[d]oxazol-5-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2,7-diazaspiro[4.4]nonan-1-one;
(S)-2-(3-(6-isopropoxypyridin-3-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-7-(2-(4-(5-(1-methyl-1H-1,2,4-triazol-3-yl)thiazol-2-yl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl-1,1-d2)-2,7-diazaspiro[4.4]nonan-1-one; and
(S)-7-(2-(4-(5-(1-methyl-1H-1,2,4-triazol-3-yl)thiazol-2-yl)-3,6-dihydropyridin-1(2H)-yl)-2-oxoethyl)-2-(3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2,7-diazaspiro[4.4]nonan-1-one;
or a pharmaceutically acceptable salt of the foregoing.
23. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, excipient, or combination thereof.