Pyrazolopyridine kinase inhibitors

1. A compound represented by a structural formula selected from the group consisting of:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is —H, halogen or C1-C10 haloalkyl;

Q is —N—, —O—, or —S—;

ring B is a 6-membered monocyclic heteroaromatic ring optionally fused to an aromatic or non-aromatic ring; and ring B is optionally substituted with one Y and independently further optionally and independently substituted with one or more J c ;

Y is —Y1-Q1;

Y1 is absent, or C1-10 aliphatic, wherein up to three methylene units of Y1 are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p ; and Y1 is optionally and independently substituted with one or more J d ;

Q1 is absent, or a C3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and Q1 is optionally and independently substituted with one or more J b ; wherein Y1 and Q1 are not both absent;

R 3 is absent, —H, or C1-C6 alkyl optionally and independently substituted with one or more J a ;

R 4 is a C1-10 aliphatic, wherein up to three methylene units of R 4 are optionally and independently replaced by G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and R 4 is optionally and independently substituted with one or more J a ;

ring C is a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur optionally and independently substituted with one Z or independently further optionally and independently substituted with one or more J b ;

Z is —Y2-Q2;

Y2 is absent, or C1-10 aliphatic, wherein up to three methylene units of Y2 are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and Y2 is optionally and independently substituted with one or more J d ;

Q2 is absent, C3-8 membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and Q2 is optionally and independently substituted with one or more J c ; wherein Y2 and Q2 are not both absent;

each R′ is independently —H, or C1-C6 alkyl optionally and independently substituted with one or more J a ;

each J a is independently halogen, —OR, —N(R) 2 , —C(O)OR, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)OR, —CN, —NO 2 , or oxo;

each J b is independently halogen, —OR, —N(R) 2 , —C(O)OR, —C(O)N(R) 2 , —NRC(O)R, —NRC(O)OR, —CN, —NO 2 , oxo, or C1-C6 alkyl optionally and independently substituted with J a ;

each J c is independently halogen, —OR′, —N(R′) 2 , —C(O)OR′, —C(O)N(R′) 2 , —NR′C(O)R′, —NR′C(O)OR′, —CN, —NO 2 , or C1-C10 aliphatic optionally and independently substituted with one or more J a , or C3-C8 cycloaliphatic optionally and independently substituted with one or more J b ;

each J d is independently halogen, —CN, or —NO 2 ;

each J e is independently halogen, —CN, —NO 2 , oxo, C1-10 aliphatic, wherein up to three methylene units are optionally and independently replaced with G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p — and the aliphatic group is optionally and independently substituted with one or more J d , or J e is C3-8 cycloaliphatic optionally and independently substituted with one ore more J b ;

each R is independently —H or C1-C6 alkyl;

each q is independently 0 or 1; and

each t is independently 0, 1, or more.

2. The compound of claim 1 wherein:

ring B is pyridyl, pyrazinyl, pyrimidinyl, isoquinolyl, quinazolinyl, pyridopyridyl, pyridopyradazinyl, pyrrolopyridiyl, pyrazolopyridiyl, pyrolopyrimidinyl, or pyrrolopyrazinyl, wherein ring B is optionally substituted with one Y and independently further and optionally and independently substituted with one or more J c .

3. The compound of claim 2 wherein:

ring B is pyridyl, pyrazinyl, pyrimidinyl, isoquinolyl, pyrrolopyridiyl, pyrazolopyridiyl, pyrolopyrimidinyl, or pyrrolopyrazinyl, wherein ring B is optionally substituted with one Y and independently further and optionally and independently substituted with one or more J c .

4. The compound of claim 3 wherein:

ring B is pyridyl optionally substituted with one Y and independently further and optionally and independently substituted with one or more J c .

5. The compound of claim 3 wherein:

ring B is pyrazinyl optionally substituted with one Y and independently further and optionally and independently substituted with one or more J c .

6. The compound of claim 4 wherein:

ring C is selected from the group consisting of cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, cyclohexenyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl, imidazolyl, pyrazolyl, oxazalolyl, oxadiazolyl, thiazolyl, thiadiazolyl, piperidinyl, piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, azepanyl, diazepanyl, triazepanyl, azocanyl, diazocanyl, triazocanyl, indolyl, indazolyl, benzimidazolyl, quinolyl, quinoxalyl, indolinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, oxazocanyl, oxazepanyl, azabicyclopentyl, azabicyclohexyl, azabicycloheptyl, azabicyclooctyl, azabicyclononyl, azabicyclodecyl, diazabicyclohexyl, diazabicycloheptyl, azetidinyl, isoindolinyl, isoindolyl, dihydroindazolyl, dihydrobenzimidazolyl, morpholinyl, tetrahydropyridyl, dihydropyridyl, tetrahydropyrazinyl, dihydropyrazinyl, tetrahydropyrimidinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydropyrazolyl, dihydroimidazolyl, octahydropyrrolopyrazyl, octahydropyrrolopyridyl, octahydropyridopyrazyl, octahydropyridopyridyl, diazabicyclooctyl, diazabicyclononyl, diazabicyclodecyl, thiazepanyl, and thiazocanyl wherein each ring is independently optionally and independently substituted with one Z and independently further and optionally substituted with one or more J b .

7. The compound of claim 4 wherein

ring C is selected from the group consisting of cyclohexyl, diazabicyclooctyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl, imidazolyl, pyrazolyl, oxazalolyl, oxadiazolyl, thiazolyl, azetidinyl, morpholinyl, azepanyl, diazabicycloheptyl, diazabicyclooctyl, indolyl, tetrahydropyridyl, dihydropyridyl, octahydropyrrolopyrazyl, octahydropyrrolopyridyl, octahydropyridopyrazyl, octahydropyridopyridyl, thiadiazolyl, piperidinyl, piperazinyl, pyrrolidinyl, diazepanyl, and oxazepanyl wherein each ring is independently optionally and independently substituted with one Z and independently further and optionally substituted with one or more J b .

8. The compound of claim 4 wherein

ring C is selected from the group consisting of cyclohexyl, 3,8-diazabicyclo[3.2.1.]octane, phenyl, pyridyl, piperidinyl, piperazinyl, diazepanyl, pyrrolidinyl, pyrrolyl, pyrrazolyl, azetidinyl, morpholinyl, azepanyl, 2,5 diazabicycloheptyl, diazabicyclooctyl, indolyl, tetrahydropyridyl, octahydro-1H-pyrrolo[2,3-b]pyrazyl, octahydropyrrolo[1,2-a]pyrazyl, and oxazepanyl wherein each ring is independently optionally and independently substituted with one Z and independently further and optionally substituted with one or more J b .

9. The compound of claim 4 wherein

ring C is selected from the group consisting of cyclohexyl, phenyl, piperidinyl, piperazinyl, diazapanyl, pyrrolidinyl, azetidinyl, and azepanyl, wherein each ring is independently optionally and independently substituted with one Z and independently further and optionally substituted with one or more J b .

10. The compound of claim 5 wherein ring C is represented a structural formula selected from the group consisting of:

q is 0 or 1; and

t is 0, 1 or more.

11. The compound of claim 5 wherein ring C is represented by a structural formula selected from the group consisting of:

q is 0 or 1; and

t is 0, or 1-4.

12. The compound of claim 11 wherein ring C is represented by a structural formula represented by:

q is 0 or 1; and

t is 0, or 1-4.

13. The compound of claim 4 wherein ring C is represented by a structural formula selected from the group consisting of:

q is 0 or 1; and

t is 0, or 1-4.

14. The compound of claim 13 wherein ring C is represented by a structural formula represented by:

q is 0 or 1; and

t is 0, or 1-4.

15. The compound of claim 13 wherein ring C is represented by a structural formula represented by:

q is 0 or 1; and

t is 0, or 1-4.

16. The compound of claim 15 wherein:

R 4 is a C1-10 aliphatic, wherein up to three methylene units of R 4 are optionally and independently replaced by G′ wherein G′ is —O—, —C(O)—, —N(R′)—, or —S(O) p —; and R 4 is optionally and independently substituted with one or more J a .

17. The compound of claim 16 wherein:

R 4 is a C2-10 aliphatic, wherein up to three methylene units of R 4 are optionally and independently replaced by G′ wherein G′ is —O—, or —N(R′)—; and R 4 is optionally and independently substituted with one or more J a .

18. The compound of claim 1 , wherein the compound represented by a structural formula selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

19. A composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

20. A method of treating a protein kinase c theta mediated condition in a subject, wherein the condition is selected from the group consisting of psoriasis or transplant rejection, comprising administering to the subject an effective amount of a compound or pharmaceutically acceptable salt thereof or composition of any one of claims 1 - 4 , 6 , 13 and 15 - 19 .