Imidazo[2,1-f][1,2,4]triazine compounds as pi3k-y inhibitors
This application relates to compounds of Formula (I): or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
1. A compound of Formula (I):
or a pharmaceutically acceptable salt or a tautomer thereof,
wherein:
L is
wherein the single wavy line indicates the point of attachment to R 10 and the double wavy line indicates the point of attachment to the 6-membered ring;
X 1 is N;
X 2 is N;
X 3 is CR 3 ;
X 4 is CR 4 ;
X 5 is CR 5 ;
X 6 is CR 6 ;
R 3 is H;
R 4 is CH 3 , CH 2 D, CHD 2 , or CD 3 ;
R 5 is H;
R 6 is H;
R 7 is H;
R 8 is H, CH 3 , or CF 3 ;
R 9 is H;
R 10 is C 1-6 alkyl, optionally substituted with 1 or 2 independently selected R b substituents;
R 11 is H, C 1-6 alkyl, or C 3-10 cycloalkyl, wherein the C 3-10 cycloalkyl is optionally substituted with 1 or 2 independently selected R q substituents;
each R b is independently OH;
each R q is independently D, halo, CN, C 1-6 alkyl, C 1-6 haloalkyl, C(O)R 12 , C(O)NHR 12 , C(O)OH, C(O)OR 12 , NH 2 , N(R 12 ) 2 , NHC(O)R 12 , NHS(O) 2 R 12 , OH, OC 1-6 alkyl, OC 1-6 haloalkyl, OC(O)R 12 , SC 1-4 alkyl, S(O) 2 R 12 , S(O) 2 NHR 12 , C 3-6 cycloalkyl, 4- to 6-membered heterocycloalkyl, phenyl, or 5- to 6-membered heteroaryl, wherein the C 1-6 alkyl, 4- to 6-membered heterocycloalkyl, phenyl, and 5- to 6-membered heteroaryl of R q are each optionally and independently substituted with one or more substituents independently selected from the group consisting of CN, C(O)OH, NH 2 , OH, OC 1-6 alkyl, C 3-6 cycloalkyl, and 4- to 6-membered heterocycloalkyl; and
each R 12 is independently C 1-6 alkyl.
2. The compound of claim 1 , wherein R 11 is H.
3. The compound of claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt or a tautomer thereof.
4. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound of claim 1 , or a pharmaceutically acceptable salt or a tautomer thereof.
5. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound of claim 3 , or a pharmaceutically acceptable salt or a tautomer thereof.
6. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt or a tautomer thereof.
7. The compound of claim 6 , wherein the compound is:
or a pharmaceutically acceptable salt or a tautomer thereof.
8. The compound of claim 6 , wherein the compound is:
or a pharmaceutically acceptable salt or a tautomer thereof.
9. The compound of claim 6 , wherein the compound is:
or a pharmaceutically acceptable salt or a tautomer thereof.
10. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound of claim 6 , or a pharmaceutically acceptable salt or a tautomer thereof.
11. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound of claim 7 , or a pharmaceutically acceptable salt or a tautomer thereof.
12. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound of claim 8 , or a pharmaceutically acceptable salt or a tautomer thereof.
13. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier and a compound of claim 9 , or a pharmaceutically acceptable salt or a tautomer thereof.