Tri-cyclic pyrazolopyridine kinase inhibitors

1. A compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein:

X is N or CH;

R 1 is selected from an optionally substituted pyridine, pyrimidine, pyrazine, pyridazine, thiazole, pyrazole, or thiadiazole ring, wherein each of said rings is optionally substituted with 1, 2, or 3 independent occurrences of R 1a ;

R 1a is chloro, fluoro, C 1-6 aliphatic, C 3-6 cycloaliphatic, —C(O)R 1b , —C(O)N(R 1b ) 2 , —C(O)O(R 1b ), —S(O)R 1b , —S(O) 2 N(R 1b ) 2 , —N(R 1b ) 2 , —N(R 1b )C(O)R 1b , —N(R 1b )S(O) 2 R 1b , —OR 1b —SR 1b , or a 5-6 membered heteroaryl or heterocyclyl having up to 3 atoms selected from nitrogen, oxygen, or sulfur, wherein each of said aliphatic or cycloaliphatic is optionally substituted with 1, 2, 3, or 4, occurrences of J R ;

each J R is independently fluoro, oxo, —C(O)R 1b , —C(O)N(R 1b ) 2 , —C(O)O(R 1b ), —N(R 1b ) 2 , —N(R 1b )C(O)R 1b , —OR 1b , —SR 1b , phenyl, or a 5-6 membered heteroaryl or heterocyclyl having up to 4 atoms selected from nitrogen, oxygen, or sulfur, wherein said phenyl, heteroaryl, or heterocyclyl or J R is optionally substituted with 1 or 2 R 1c groups;

each R 1b is independently selected from hydrogen, C 1-4 aliphatic, C 3-6 cycloaliphatic, phenyl, benzyl, wherein each of said aliphatic, cycloaliphatic, phenyl, or benzyl of J R1 is optionally substituted with up to three R 1c groups;

each R 1c is independently selected from chloro, fluoro, oxo, C 1-2 alkyl, C 1-2 alkyl substituted with 1-3 fluorine atoms, C 3-6 cycloalkyl, —OH, —OC 1-2 alkyl, or —OC 1-2 alkyl substituted with 1-3 fluorine atoms;

R 2 is hydrogen, fluoro, chloro, C 1-6 aliphatic, —OC 1-6 aliphatic, C 3-6 cycloaliphatic, —OC 3-6 cycloaliphatic, cyano, —NH 2 , —NHC 1-6 aliphatic, —NHC 3-6 cycloaliphatic, —NHS(O) 2 C 1-6 aliphatic, —NHS(O) 2 C 3-6 cycloaliphatic, —NHS(O) 2 phenyl, —NHS(O) 2 benzyl, —NHS(O) 2 heteroaryl, —S(O) 2 C 1-6 aliphatic, —S(O) 2 C 3-6 cycloaliphatic, —S(O) 2 phenyl, —S(O) 2 benzyl, —S(O) 2 heteroaryl, —S(O) 2 NHC 1-6 aliphatic, —S(O) 2 NHC 3-6 cycloaliphatic, —S(O) 2 NHphenyl, —S(O) 2 NHbenzyl, or —S(O) 2 NHheteroaryl, wherein said heteroaryl of R 2 is a 5- or 6-membered ring having 1, 2, or 3 atoms selected from N, O, or S, and wherein said aliphatic, cycloaliphatic, phenyl, benzyl, or heteroaryl of R 2 is optionally substituted with 1, 2, or 3 R 2a groups;

each R 2a is selected from chloro, fluoro, oxo, C 1-2 alkyl, C 1-2 alkyl substituted with 1-3 fluorine atoms, C 3-6 cycloalkyl, —OH, —OC 1-2 alkyl, or —OC 1-2 alkyl substituted with 1-3 fluorine atoms; and

R 3 is hydrogen, fluoro, chloro, C 1-3 aliphatic, cyclopropyl, —OC 1-3 aliphatic, NH 2 , or NHC 1-3 aliphatic, wherein said aliphatic of R 3 is optionally substituted with up to 3 occurrences of fluoro.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is N.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein each of R 2 and R 3 is a C 1-3 aliphatic or —OC 1-3 alkyl optionally substituted with up to three R 2a groups.

5. The compound according to claim 1 , wherein R 2 is —OC 1-3 alkyl.

6. The compound according to claim 1 , wherein R 2 is —CF 3 .

7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein

8. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein said compound is selected from:

9. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

10. The composition according to claim 9 , additionally comprising a therapeutic agent selected from an agent for treating multiple sclerosis, an anti-inflammatory agent, an immunomodulatory agent, or an immunosuppressive agent.

11. A method of inhibiting PI3K-gamma kinase activity in a biological sample comprising contacting said biological sample with a compound according to claim 1 or a composition according to claim 9 .