Compounds useful as inhibitors of ATR kinase

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof wherein:

R 1 is a 5-6 membered monocyclic aryl or heteroaryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein said monocyclic aryl or heteroaryl ring is optionally fused to another ring to form a 8-10 membered bicyclic aryl or heteroaryl ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1 is optionally substituted with 1-5 J 1 groups;

C 2 , C 3 and C 5 are carbon;

R 2 is -Q or -Q-Q 1 ;

Q is a 3-7 membered monocyclic saturated or unsaturated non-aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q is independently and optionally substituted with 1-4 J Q groups; Q is substituted with zero to two occurrences of J;

Q is optionally fused to Q 1 to form a fused bicyclic ring Q-Q 1 ; or Q and Q 1 are optionally joined together at a carbon atom to form a spirocyclic bicyclic ring Q-Q 1 ; or Q and Q 1 , taken together, form a bridged bicyclic ring Q-Q 1 wherein said bridge is 1-3 atoms long; Q-Q 1 can be optionally substituted with 1-2 J groups; wherein J can be bonded to either Q or Q 1 ;

Q 1 is a 3-8 membered monocyclic saturated or unsaturated ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 1 is independently and optionally substituted with 1-4 J Q1 groups;

J is halo, oxo, —CN, —NO 2 , V 1 —R″, or —(V) m —R*;

R″ is H or a 3-8 membered saturated or unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered saturated or unsaturated bicyclic ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R″ is optionally substituted with 1-5 J′;

L is —C(O)NH—or —C(O)N(C 1-6 alkyl)-;

n is 0 or 1;

each J Q and J Q1 is independently halo, oxo, —CN, —NO 2 , V—R, or —(V) m -Q 2 ;

J 1 is halo, —CN, —NO 2 , V—R, or —(V 2 ) m -Q 3 ;

V is a C 1-10 aliphatic chain wherein 0-3 methylene units are optionally and independently replaced with oxygen, nitrogen, sulfur, C(O), S(O), or S(O) 2 ; V is optionally substituted with 1-6 occurrences of J V ;

V 1 is a C 1-10 aliphatic chain wherein 0-3 methylene units are optionally replaced with —NR′—, —O—, —S—, C(O), S(O), or S(O) 2 ; V 1 is optionally substituted with 1-6 occurrences of J V1 ;

m is 0 or 1;

V 2 is a C 1-10 aliphatic chain wherein 0-3 methylene units are optionally and independently replaced with oxygen, nitrogen, sulfur, C(O), S(O), or S(O) 2 ; V is optionally substituted with 1-6 occurrences of J V2 ;

m is 0 or 1;

Q 2 is a 3-8 membered saturated or unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered saturated or unsaturated bicyclic ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 2 is optionally substituted with 1-5 J Q2 ;

Q 3 is a 3-8 membered saturated or unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered saturated or unsaturated bicyclic ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 3 is optionally substituted with 1-5 J Q3 ;

each J V , J V1 , and J V2 is independently halogen, CN, NH 2 , NO 2 , C 1-4 aliphatic, NH(C 1-4 aliphatic) N(C 1-4 aliphatic) 2 , OH, O(C 1-4 aliphatic), CO 2 H, CO 2 (C 1-4 aliphatic), C(O)NH 2 , C(O)NH(C 1-4 aliphatic), C(O)N(C 1-4 aliphatic) 2 ,NHCO(C 1-4 aliphatic), N(C 1-4 aliphatic)CO(C 1-4 aliphatic), SO 2 (C 1-4 aliphatic), NHSO 2 (C 1-4 aliphatic), or N(C 1-4 aliphatic)SO 2 (C 1-4 aliphatic), wherein said C 1-4 aliphatic is optionally substituted with halo;

each J Q2 and J Q3 is independently halo, oxo, CN, NO 2 , X—R, or —(X) p -Q 4 ,

p is 0 or 1;

X is C 1-10 aliphatic; wherein 1-3 methylene units of said C 1-6 aliphatic are optionally replaced with —NR, —O—, —S—, C(O), S(O) 2 , or S(O); wherein X is optionally and independently substituted with 1-4 occurrences of NH 2 , NH(C 1-4 aliphatic), N(C 1-4 aliphatic) 2 , halogen, C 1-4 aliphatic, OH, O(C 1-4 aliphatic), NO 2 , CN, CO 2 H, CO 2 (C 1-4 aliphatic), C(O)NH 2 , C(O)NH(C 1-4 aliphatic), C(O)N(C 1-4 aliphatic) 2 , SO(C 1-4 aliphatic), SO 2 (C 1-4 aliphatic), SO 2 NH(C 1-4 aliphatic), SO 2 NH(C 1-4 aliphatic), NHC(O)(C 1-4 aliphatic), N(C 1-4 aliphatic)C(O)(C 1-4 aliphatic), wherein said C 1-4 aliphatic is optionally substituted with 1-3 occurrences of halo;

Q 4 is a 3-8 membered saturated or unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered saturated or unsaturated bicyclic ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 4 is optionally substituted with 1-5 J Q4 ;

J Q4 is halo, CN, or C 1-4 alkyl wherein up to 2 methylene units are optionally replaced with O, N, S, C(O), S(O), or S(O) 2 ;

each R*, R′, and R is independently H or C 1-4 alkyl wherein said C 1-4 alkyl is optionally substituted with 1-4 halo.

2. The compound of claim 1 , wherein

R 1 is a 5-6 membered monocyclic aryl or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein said monocyclic aryl or heteroaryl ring is optionally fused to another ring to form a 8-10 membered bicyclic aryl or heteroaryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1 is optionally substituted with 1-5 J 1 groups;

Q is a 3-7 membered monocyclic saturated or partially unsaturated non-aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Q can be optionally fused to Q 1 ; each Q is independently and optionally substituted with 1-4 J Q groups; Q is substituted with one to two occurrences of J;

Q 1 is a 5-8 membered monocyclic saturated or unsaturated ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 1 is independently and optionally substituted with 1-4 J Q1 groups;

J is fluoro oxo, —CN, —NO 2 , V 1 —R″, or —(V) m —R*;

L is —C(O)NH—;

each J Q and J Q1 is independently halo, —CN, —NO 2 , V—R, or —(V) m -Q 2 ;

each J Q2 and J Q3 is independently halogen, NO 2 , CN, or C 1-6 aliphatic wherein up to 1 methylene unit is optionally replaced with N(R) 2 , OR, SR, COR, CO 2 R, CON(R) 2 , SOR, SO 2 R, SO 2 N(R) 2 , OCOR, NRCOR, NRCOOR, NRSOR, NRSO 2 R, NRSO 2 N(R) 2 , OCON(R) 2 , or NRCON(R) 2 ; wherein said C 1-6 aliphatic is optionally substituted with 1-4 substituents selected from NH 2 , NH(C 1-4 aliphatic), N(C 1-4 aliphatic) 2 , halogen, C 1-4 aliphatic, OH, O(C 1-4 aliphatic), NO 2 , CN, CO 2 H, CO 2 (C 1-4 aliphatic), O(haloC 1-4 aliphatic), or haloC 1-4 aliphatic;

each J V is independently NH 2 , NH(C 1-4 aliphatic), N(C 1-4 aliphatic) 2 , halogen, C 1-4 aliphatic, OH, O(C 1-4 aliphatic), NO 2 , CN, CO 2 H, CO 2 (C 1-4 aliphatic), O(haloC 1-4 aliphatic), or haloC 1-4 aliphatic.

3. The compound of claim 2 , wherein

J is oxo or (V 1 )—R″;

V 1 is C 1-6 aliphatic chain wherein up to three methylene unit of the aliphatic chain may be optionally replaced with —NR′—, —O—, —S—, —C(O)—, —S(O)—, or —S(O) 2 —; wherein the first or second methylene group away from the point of attachment is replaced with CO, SO, SO 2 , S, or O;

R′ is H or C 1-4 alkyl;

R″ is H or a 5-6 membered monocyclic ring containing 0-2 heteroatoms selected from O, N, or S; wherein said R″ is optionally substituted with 1-3 occurrences of halo, C 1-3 alkyl, CN, OH, O(C 1-3 alkyl), NH 2 , NH(C 1-3 alkyl), N(C 1-3 alkyl) 2 , or acetyl.

4. The compound of claim 2 , wherein R 1 is

5. The compound of claim 2 , wherein Q is C 3-7 cycloalkyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, homopiperidinyl, morpholinyl, or thiomorpholinyl.

6. The compound of claim 2 , wherein Q is

7. The compound of claim 2 , wherein J is C 1-6 aliphatic chain wherein up to 2 methylene units of C 1-6 aliphatic optionally replaced with heteroatom selected from O, N, or S.

8. A compound of formula Ia:

or a pharmaceutically acceptable salt thereof wherein:

R 1 is a 5-6 membered monocyclic aryl or heteroaryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein said monocyclic aryl or heteroaryl ring is optionally fused to another ring to form a 8-10 membered bicyclic aryl or heteroaryl ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R 1 is optionally substituted with 1-5 J 1 groups;

R 2 is -Q or -Q-Q 1 ;

Q is a 3-7 membered monocyclic saturated or unsaturated non-aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Q is optionally substituted with 1-4 J Q groups; Q is optionally substituted with 1-2 J groups;

Q 1 is a 3-8 membered monocyclic saturated or unsaturated ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 1 is independently and optionally substituted with 1-4 J Q1 groups;

Q is optionally fused to Q 1 to form a fused bicyclic ring Q-Q 1 ; or Q and Q 1 are optionally joined together at a carbon atom to form a spirocyclic bicyclic ring Q-Q 1 ; or Q and Q 1 , taken together, form a bridged bicyclic ring Q-Q 1 wherein said bridge is 1-3 atoms long; Q-Q 1 can be optionally substituted with 1-2 J groups; wherein J can be bonded to either Q or Q 1 ;

each J Q and J Q1 is independently halo, oxo, —CN, —NO 2 , V—R, or —(V) m -Q 2 ;

J is halo, oxo, —CN, —NO 2 , V 1 —R″, or —(V) m —R*;

L is —C(O)NH— or —C(O)N(C 1-6 alkyl)—;

n is 0 or 1;

J 1 is halo, —CN, —NO 2 , V—R, or —(V 2 ) m -Q 3 ;

V is a C 1-10 aliphatic chain wherein 0-3 methylene units are optionally replaced with —NR—, —O—, —S—, C(O), S(O), or S(O) 2 ; V is optionally substituted with 1-6 occurrences of J V ;

V 1 is a C 1-10 aliphatic chain wherein 0-3 methylene units are optionally replaced with —NR′—, —O—, —S—, C(O), S(O), or S(O) 2 ; V 1 is optionally substituted with 1-6 occurrences of J V1 ;

V 2 is a C 1-10 aliphatic chain wherein 0-3 methylene units are optionally and independently replaced with —NR—, —O—, —S—, C(O), S(O), or S(O) 2 ; V 2 is optionally substituted with 1-6 occurrences of J V2 ;

m is 0 or 1;

Q 2 is a 3-8 membered saturated or unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered saturated or unsaturated bicyclic ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 2 is optionally substituted with 1-5 J Q2 ;

Q 3 is a 3-8 membered saturated or unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered saturated or unsaturated bicyclic ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each Q 3 is optionally substituted with 1-5 J Q3 ;

R″ is a 3-8 membered saturated or unsaturated monocyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered saturated or unsaturated bicyclic ring having 0-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R″ is optionally substituted with 1-5 J′;

each J V , J V1 and J V2 is independently halogen, CN, NH 2 , NO 2 , C 1-4 aliphatic, NH(C 1-4 aliphatic), N(C 1-4 aliphatic) 2 , OH, O(C 1-4 aliphatic), CO 2 H, CO 2 (C 1-4 aliphatic), C(O)NH 2 , C(O)NH(C 1-4 aliphatic), C(O)N(C 1-4 aliphatic) 2 , NHCO(C 1-4 aliphatic), N(C 1-4 aliphatic)CO(C 1-4 aliphatic), SO 2 (C 1-4 aliphatic), NHSO 2 (C 1-4 aliphatic), or N(C 1-4 aliphatic)SO 2 (C 1-4 aliphatic), wherein said C 1-4 -aliphatic is optionally substituted with halo;

each J Q2 , J Q3 , and J′ is independently halo, oxo, CN, NO 2 , X—R, or —(X) p -Q 4 ,

p is 0 or 1;

X is a C 1-10 aliphatic; wherein 1-3 methylene units of said C 1-6 aliphatic are optionally replaced with —NR, —O—, —S—, C(O), S(O) 2 , or S(O); wherein X is optionally and independently substituted with 1-4 occurrences of NH 2 , NH(C 1-4 aliphatic), N(C 1-4 aliphatic) 2 , halogen, C 1-4 aliphatic, OH, O(C 1-4 aliphatic), NO 2 , CN, CO 2 H, CO 2 (C 1-4 aliphatic), C(O)NH 2 , C(O)NH(C 1-4 aliphatic), C(O)N(C 1-4 aliphatic) 2 , SO(C 1-4aliphatic), SO 2 (C 1-4 aliphatic), SO 2 NH(C 1-4 aliphatic), SO 2 N(C 1-4 aliphatic) 2 , NHC(O)(C 1-4 aliphatic), or N(C 1-4 aliphatic)C(O)(C 1-4 aliphatic), wherein said C 1-4 aliphatic is optionally substituted with 1-3 occurrences of halo;

Q 4 is a 3-6 membered monocyclic ring containing 0-2 heteroatoms selected from O, N, or S; each Q 4 is optionally substituted with J Q4 ;

J Q4 is halo, CN, or C 1-4 alkyl wherein up to 2 methylene units are optionally replaced with O, N, S, C(O), S(O), or S(O) 2 ;

each R*, R′, and R is independently H or C 1-4 alkyl wherein said C 1-4 alkyl is optionally substituted with 1-4 halo.

9. The compound of claim 8 , wherein each J Q and J Q1 is independently halo, oxo, —CN, —NO 2 , or V—R.

10. The compound of claim 8 , wherein Q or Q 1 is substituted with 1-2 occurrences of J.

11. The compound of claim 10 , wherein Q or Q 1 is substituted with zero occurrences of J Q and J Q1 and Q is substituted with 1 occurrence of J.

12. The compound of claim 10 , wherein

each J is independently oxo, (V 1 )—R″ or —(V) m —R*;

each V and V 1 is independently a C 1-6 aliphatic chain wherein up to three methylene unit of the aliphatic chain may be optionally replaced with —NR′—, —O—, —S—, —C(O)—, —S(O)—, or —S(O) 2 —; wherein the first or second methylene group away from the point of attachment is replaced with —C(O)—, —S(O)—, —S(O) 2 —, —S—, or —O—;

each J V and J V1 is independently halo or C 1-4 alkyl;

R′ is H or C 1-4 alkyl;

R* is H or C 1-4 alkyl;

R″ is a 3-7 membered monocyclic ring containing 0-2 heteroatoms selected from O, N, or S; wherein said R″ is optionally substituted with 1-3 occurrences of J′;

J′ is oxo, halo, C 1-3 alkyl, haloC 1-3 alkyl, CN, OH, O(C 1-3 alkyl), NH 2 , NH(C 1-3 alkyl), N(C 1-3 alkyl) 2 , or acetyl.

13. The compound of claim 8 , wherein Q contains sulfur, nitrogen, or oxygen as a ring member.

14. The compound of claim 13 , wherein Q contains nitrogen as a ring member.

15. The compound of claim 14 , wherein

said nitrogen of Q is substituted with one occurrence of J Q ;

J Q is phenyl, pyridyl, pyrimidyl, thiazolyl, C 1-6 aliphatic, or benzyl; wherein J Q is optionally substituted with 1-3 occurrences of J Q2 ;

J Q2 is halo, haloC 1-6 aliphatic, CN, NO 2 , or C 1-6 aliphatic, wherein 1-3 methylene units of said C 1-6 aliphatic are optionally replaced with —NH—, —O—, —S—, C(O), S(O) 2 , or S(O).

16. The compound of claim 8 , wherein n is 1.

17. The compound of claim 16 , wherein R 1 is a bicyclic ring.

18. The compound of claim 17 , wherein said ring is a 8-9 membered heteroaryl containing 1-4 heteroatoms selected from O, N, or S.

19. The compound of claim 18 , wherein said heteroatom is nitrogen.

20. The compound according to claim 18 , wherein said ring is selected from benzimidazolyl, benzoxazolyl, indazolyl, benzothiazolyl, indolyl, benzotriazolyl, pyrrolopyridyl, imidazopyridyl, or triazolopyridyl.

21. The compound of claim 16 , wherein R 1 is a monocyclic 5-6-membered ring.

22. The compound of claim 21 , wherein R 1 is pyrazolyl, phenyl, pyridyl, or pyrazinyl.

23. The compound of claim 8 , wherein n is 0.

24. The compound of claim 23 , wherein R 1 is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 8-10 membered bicyclic heteroaryl ring having 1-6 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R 1 is optionally substituted with 1-5 J 1 groups.

25. The compound of claim 24 , wherein R 1 is a 6-membered monocyclic ring selected from pyrimidyl or pyridyl.

26. The compound of claim 24 , wherein R 1 is a monocyclic 5-membered heteroaryl ring containing 1-3 heteroatoms selected from oxygen, nitrogen, or sulfur; or R 1 is a 5-membered heteroaryl ring containing 1-2 heteroatoms selected from oxygen, nitrogen, or sulfur fused to a 6-membered aryl or heteroaryl ring containing 0-4 nitrogen atoms.

27. The compound of claim 23 , wherein said ring heteroatom (shown as G) is located next to the carbon atom bonded to C 3 as shown below in formula II:

28. The compound of claim 27 , wherein R 1 is a 5-membered ring optionally fused to another ring or a monocyclic 5-membered ring containing 1-3 heteroatoms selected from oxygen, nitrogen, or sulfur.

29. The compound of claim 28 , wherein R 1 is a 5-membered ring and is selected from the following:

wherein each R 1 is optionally substituted with 1-2 occurrences of J 1 .

30. The compound of claim 29 , wherein R 1 is selected from the following:

31. The compound of claim 30 , wherein R 1 is,

32. The compound of claim 31 , wherein R 1 is

33. The compound of claim 32 , wherein J 1 is C 1-4 alkyl, cyclohexyl, phenyl, thienyl, furanyl, or NH-phenyl.

34. The compound of claim 33 , wherein J 1 is phenyl.

35. The compound of claim 34 , wherein the phenyl of J 1 is optionally substituted with 1-3 occurrences of J Q3 ; wherein J Q3 is selected from halo, CN, NO 2 , X—R, or —(X) p -Q 4 ; p is 0-1; X is a C 1-10 aliphatic wherein 1-3 methylene units of said C 1-6 aliphatic are optionally replaced with —NR, —O—, —S—, C(O), S(O) 2 , or S(O); R is H; and Q 4 is a 3-6 membered monocyclic ring containing 0-2 heteroatoms selected from O or N, wherein X is optionally substituted with 1-3 occurrences of halo or CN.

36. The compound of claim 35 , wherein J Q3 is a C 1-10 aliphatic chain wherein 1-2 methylene units of X are replaced with —O— or —NR—.

37. The compound of claim 35 , wherein Q 4 is an optionally substituted 3-6 membered cycloalkyl ring.

38. The compound of claim 35 , wherein J Q3 is halo, OH, NH 2 , CH 2 NH 2 , CH(CH 3 )NH 2 , CH(CH 3 )NHCH 3 , C(CH 3 ) 2 NH 2 , CH 2 CH 2 NH 2 , CH 2 NHCH 3 , CH 2 N(CH 3 ) 2 , CH(CH 3 )NH 2 , CH 2 NHC(CH 3 ) 2 , CH 2 NHCH 2 CHF 2 , CH 2 NHCH 2 CH(CH 3 )OH, CH 2 NHCH 2 C(CH 3 ) 2 OH, CH 2 NHCH 2 CH(OH)-cyclopropyl, CH 2 NHCH 2 CH 2 N(CH 3 ) 2 , CH 2 NHCH(CH 2 CH 3 ) 3 , CH 2 NHCH 3 , CH 2 NHCH 2 CH 3 , CH 2 NHCH 2 CH 2 CH 3 , CH 2 NH-cyclopropyl, CH 2 NHCH 2 CH 2 OH, CH 2 NHCH 2 CH 2 OCH 3 , CH 2 NHCH 2 CH 2 OCH 2 CH 2 OH, azetidinyl or pyrrolidinyl.

39. The compound of claim 23 , wherein R 1 is selected from benzimidazolyl, imidazopyridyl, triazolopyridyl, benzofuranyl, or benzothiazolyl.

40. The compound of claim 39 , wherein R 1 is selected from:

wherein each R 1 is optionally substituted with 1-2 occurrences of J 1 ;

A is C or N, provided that at least two occurrence of A are carbon; and

X 1 is O, N, or S.

41. The compound of claim 40 , wherein R 1 is

wherein each R 1 is optionally substituted with 1-2 occurrences of J 1 ; A is carbon or nitrogen; and X 1 is selected from O, N, or S.

42. The compound of claim 41 , wherein R 1 is benzimidazolyl.

43. The compound of claim 8 , wherein R 2 is Q.

44. The compound of claim 43 , wherein Q is C 3-7 cycloalkyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, homopiperidinyl, morpholinyl, or thiomorpholinyl.

45. The compound of claim 8 , wherein Q is bonded through a carbon atom.

46. The compound of claim 45 , wherein Q is

47. The compound of claim 45 , wherein Q or Q-Q 1 is selected from the following:

C 3-8 cycloaliphatic ring,

 wherein said C 1-4 aliphatic bonded to the pyridone is optionally substituted with halo, haloC 1-3 alkyl, CN, OH, O(C 1-3 alkyl), NH 2 , NH(C 1-3 alkyl), N(C 1-3 alkyl) 2 , or acetyl.

48. The compound of claim 47 , wherein Q is optionally substituted

49. The compound of claim 45 , wherein Q is

50. The compound of claim 8 , wherein Q is bonded through a nitrogen atom.

51. The compound of claim 50 , wherein Q is optionally substituted azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, homopiperidinyl, morpholinyl, or thiomorpholinyl, wherein said Q is optionally fused to Q 1 to form a fused bicyclic ring Q-Q 1 ; or Q and Q 1 are optionally joined together at a carbon atom to form a spirocyclic bicyclic ring Q-Q 1 ; or Q and Q 1 , taken together, form a bridged bicyclic ring Q-Q 1 wherein said bridge is 1-3 atoms long; Q-Q 1 can be optionally substituted with 1-2 J groups; wherein J can be bonded to either Q or Q 1 .

52. The compound of claim 51 , wherein Q is an optionally substituted group selected from the following:

53. The compound of claim 52 , wherein J is bonded in the position of Q as shown below:

wherein Q is optionally substituted with 1-4 occurrences of J Q .

54. The compound of claim 51 , wherein Q and Q 1 together combine to form a bicyclic ring selected from the group consisting of

wherein each Q or Q 1 is optionally and independently substituted with 1-2 occurrences of J Q or J Q1 respectively and optionally with 1 occurrence of J.

55. The compound of claim 54 , wherein J is bonded in the position of Q or Q 1 as shown below:

wherein Q is optionally substituted with 1-4 occurrences of J Q or J Q1 respectively.

56. The compound of claim 23 , wherein J is C 1-6 aliphatic chain wherein up to 2 methylene units of C 1-6 aliphatic optionally replaced with heteroatom selected from O, N, or S.

57. The compound of claim 8 , wherein J is oxo, V 1 —R″, or —(V) m —R*; wherein

each V and V 1 is independently a C 1-6 alkylidene chain wherein 0-3 methylene units are replaced with O, N, S, CO, SO, or SO 2 ;

R* is H or C 1-6 alkyl;

m is 0 or 1; and

R″ is a 3-7 membered saturated or unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

58. The compound of claim 57 , wherein R 2 is piperazine or tetrahydropyridinyl; m is 0; J is oxo, V 1 —R″, or —(V)—R*, wherein R″ is thiazolyl, pyridyl, pyrimidyl, phenyl; and R* is optionally substituted with halo, O(C 1-4 alkyl), haloC 1-4 alkyl, or CN.

59. The compound of claim 57 , wherein

V is O, O(C 1-6 alkyl), (C 1-4 alkyl)O, C(O)O, C(O)O(C 1-6 alkyl), C(O)O(C 1-6 alkyl)O(C 1-6 alkyl), C(O)(C 1-6 alkyl), C(O)(C 1-6 alkyl)N, C(O)(C 1-6 alkyl)NH(C 1-6 alkyl), C(O)(C 1-6 alkyl)C(O)O, C(O)(C 1-6 alkyl)O, C(O)(C 1-6 alkyl)O(C 1-6 alkyl), C(O)(C 1-6 alkyl)NH(C 1-6 alkyl), C(O)(C 1-6 alkyl)O(C 1-4 alkyl)O(C 1-6 alkyl), C(O)NH, C(O)NH(C 1-6 alkyl), C(O)N(C 1-6 alkyl), NH, N(C 1-6 alkyl), N(C 1-6 alkyl) 2 , NHC(O), NHC(O)C 1-6 alkyl, NHC(O)(C 1-6 alkyl)O, NHC(O)(C 1-6 alkyl)O(C 1-6 alkyl), NHC(O)(C 1-6 alkyl)O(C 1-6 alkyl)O(C 1-6 alkyl), NHC(O)(C 1-6 alkyl)NH(C 1-6 alkyl), C(O)N(C 1-6 alkyl)-, C(O)N(C 1-6 alkyl) 2 , SO 2 , S(O) 2 (C 1-6 alkyl)-, S(O) 2 (C 1-6 alkyl)NH, S(O) 2 NH(C 1-6 alkyl)-, S(O) 2 N(C 1-6 alkyl) 2 , NHSO 2 , or NHSO 2 N(C 1-6 alkyl) 2 ;

R* is H or C 1-6 alkyl; and

R″ is C 3 -C 8 cycloaliphatic, imidazolyl, thienyl, thiazolyl, furanyl, pyrazolyl, triazolyl, pyrrolyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, morpholinyl, thiomorpholinyl, or tetrahydropyranyl.

60. The compound of claim 59 , wherein

V is O, OCH 2 , CH 2 O, C(O), C(O)CH 2 , C(O)CH 2 CH 2 NH, C(O)CH 2 CH 2 NHCH 2 , C(O)CH 2 CH 2 C(O)O, C(O)CH 2 O, C(O)CH 2 OCH 2 , C(O)CH 2 N(CH 3 )CH 2 , C(O)CH 2 OCH 2 CH 2 OCH 2 , C(O)CH(CH 3 )CH 2 , C(O)CH(CH 2 CH 3 )CH 2 CH 2 , C(O)O, C(O)OCH 2 , C(O)OCH 2 CH 2 , C(O)OCH 2 CH 2 OCH 2 , C(O)OCH 2 C≡C—CH 2 , C(O)NH, C(O)NHCH 2 , C(O)N(CH 3 )—, C(O)N(CH 3 )CH 2 —, NH, N(C 1-6 aliphatic), N(CH 3 )CH 2 , NHC(O), NHC(O)CH 2 , NHC(O)CH 2 O, NHC(O)CH 2 OCH 2 , NHC(O)CH 2 OCH 2 CH 2 OCH 2 , NHC(O)CH 2 N(CH 3 )CH 2 , NHC(O)C(CH 3 ) 2 CH 2 , NHC(O)CH(CH 2 CH 3 )CH 2 CH 2 , SO 2 , S(O) 2 CH 2 , S(O) 2 CH 2 CH 2 , S(O) 2 CH 2 CH 2 NH, S(O) 2 CH 2 CH 2 CH 2 NH, S(O) 2 CH 2 CH 2 CH 2 , S(O) 2 CH(CH 3 )CH 2 , S(O) 2 N(CH 3 )CH 2 , NHSO 2 , or NHSO 2 N(CH 3 )CH 2 ;

R is H or C 1-6 alkyl; and

Q 2 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, imidazolyl, thienyl, thiazolyl, furanyl, pyrazolyl, triazolyl, tetrazolyl, pyrrolyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl, homopiperazinyl, morpholinyl, thiomorpholinyl, or tetrahydropyranyl; wherein said Q 2 is optionally substituted with C 1-6 alkyl, CN, halo, haloC 1-4 alkyl, NH(C 1-4 alkyl), N(C 1-4 alkyl) 2 , or O(C 1-6 alkyl).

61. The compound of claim 23 , wherein J is selected from C 1-6 aliphatic, oxo, —OH, —O(C 1-6 aliphatic), CN, —C(O)(C 1-6 aliphatic), —C(O)(phenyl), —C(O)(benzyl), —C(O)CH 2 O(phenyl), —C(O)CH 2 O(C 1-6 aliphatic), —C(O)CH 2 O(benzyl), —C(O)(pyridyl), —C(O)(pyrrolidinyl), —C(O)(piperidinyl), —C(O)(piperazinyl), —C(O)(homopiperazinyl), —C(O)(morpholinyl), —C(O)(tetrahydropyranyl), —C(O)O(C 1-6 aliphatic), —C(O)O(phenyl), —C(O)O(benzyl), —C(O)NH 2 , —C(O)NH(C 1-6 aliphatic), —C(O)N(C 1-6 aliphatic) 2 , —C(O)NH(phenyl), —C(O)NH(benzyl), —S(O) 2 (C 1-6 aliphatic), —S(O) 2 (phenyl), —S(O) 2 (benzyl), —S(O) 2 (pyridyl), —S(O) 2 (furanyl), —S(O) 2 (imidazolyl), —S(O) 2 (thienyl), —S(O) 2 NH(C 1-6 aliphatic), —S(O) 2 N(C 1-6 aliphatic) 2 , —S(O) 2 NH(phenyl), —S(O) 2 NH(benzyl), —NHC(O)(C 1-6 aliphatic), —NHC(O)(pyridyl), NHS(O) 2 N(C 1-6 aliphatic) 2 , NH 2 , NH(C 1-6 aliphatic), N(C 1-6 aliphatic) 2 ; wherein said phenyl, benzyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, or C 1-6 aliphatic is optionally substituted with halo, C 1-3 alkyl, CN, OH, O(C 1-3 alkyl), NH 2 , NH(C 1-3 alkyl), N(C 1-3 alkyl) 2 , acetyl, SO 2 (C 1-3 alkyl).

62. The compound of claim 61 , wherein J is selected from, oxo, —OH, —NHC(O)(C 1-4 alkyl), —C(O)(C 1-4 alkyl), —C(O)NH 2 , —C(O)NH(C 1-4 alkyl), —C(O)NH(C 1-4 alkyl) 2 , —S(O) 2 (C 1-4 alkyl), —S(O) 2 NH(C 1-4 alkyl), or —S(O) 2 N(C 1-4 alkyl) 2 .

63. The compound of claim 23 , wherein J is selected from —C(O)CH 2 (phenyl), NH 2 , NH(C 1-3 alkyl), N(C 1-3 alkyl) 2 , —NHS(O) 2 (phenyl), —NHC(O)(phenyl), —NHC(O)(pyridyl), —C(O)CH 2 O(phenyl), —C(O)CH 2 O(C 1 -3 alkyl), —NHC(O)CH 2 O(C 1-3 alkyl), —NHC(O)CH 2 O(phenyl), —C(O)CH 2 N(C 1-3 alkyl) 2 , —NHC(O)CH 2 N(C 1-3 alkyl) 2 , —C(O)CH 2 O(C 1-3 alkyl)O(C 1 -3 alkyl), —NHC(O)CH 2 O(C 1-3 alkyl)O(C 1-3 alkyl), —C(O)O(C 1-3 alkyl)O(C 1 -3 alkyl), phenyl, pyridyl, thiazolyl, CF 3 , pyrimidiyl, wherein said phenyl, pyridyl, or pyrimidyl group is optionally substituted with halo, O(C 1-6 aliphatic), CN, CF 3 , C(O)(furanyl).

64. The compound of claim 1 selected from the following:

I-1 

I-2 

I-3 

I-4 

I-5 

I-6 

I-7 

I-8 

I-9 

I-10

I-11

I-12

I-13

I-14

I-15

I-16

I-17

I-18

I-19

I-20

I-21

I-22

I-23

I-24

I-25

65. The compound of claim 1 selected from the following:

I-26

I-27

I-28

66. The compound of claim 1 selected from the following:

I-29 

I-30 

I-31 

I-32 

I-33 

I-34 

I-35 

I-36 

I-37 

I-38 

I-39 

I-40 

I-41 

I-42 

I-43 

I-44 

I-45 

I-46 

I-47 

I-48 

I-49 

I-50 

I-51 

I-52 

I-53 

I-54 

I-55 

I-56 

I-57 

I-58 

I-59 

I-60 

I-61 

I-62 

I-63 

I-64 

I-65 

I-66 

I-67 

I-68 

I-69 

I-70 

I-71 

I-72 

I-73 

I-74 

I-75 

I-76 

I-77 

I-78 

I-79 

I-80 

I-81 

I-82 

I-83 

I-84 

I-85 

I-86 

I-87 

I-88 

I-89 

I-90 

I-91 

I-92 

I-93 

I-94 

I-95 

I-96 

I-97 

I-98 

I-99 

I-100

I-101

I-102

I-103

I-104

I-105

I-106

I-107

I-108

I-109

I-110

I-111

I-112

I-113

I-114

I-115

I-116

I-117

I-118

I-119

I-120

I-121

I-122

I-123

I-124

I-125

I-126

I-127

I-128

I-129

I-130

I-131

I-132

I-133

I-134

I-135

I-136

I-137

I-138

I-139

I-140

I-141

I-142

I-143

I-144

I-145

I-146

I-147

I-148

I-149

I-150

I-151

I-152

I-153

I-154

I-155

I-156

I-157

I-158

I-159

I-160

I-161

I-162

I-163

I-164

I-165

I-166

I-167

I-168

I-169

I-170

I-171

I-172

I-173

67. The compound of claim 1 selected from the following:

I-174

I-175

I-176

I-177

I-178

I-179

I-180

I-181

I-182

I-183

I-184

I-185

I-186

I-187

I-188

I-189

I-190

I-191

I-192

I-193

I-194

I-195

I-196

I-197

I-198

I-199

I-200

I-201

I-202

I-203

I-204

I-205

I-206

I-207

I-208

I-209

I-210

I-211

I-212

I-213

I-214

I-215

I-216

I-217

I-218

I-219

I-220

I-221

I-222

I-223

I-224

I-225

I-226

I-227

I-228

I-229

I-230

I-231

I-232

I-233

I-234

I-235

I-236

I-237

I-238

I-239

I-240

I-241

I-242

I-243

I-244

I-245

I-246

I-247

I-248

I-249

I-250

I-251

I-252

I-253

I-254

I-255

I-256

I-257

I-258

I-259

I-260

I-261

I-262

I-263

I-264

I-265

I-266

I-267

I-268

I-269

I-270

I-271

I-272

I-273

I-274

I-275

I-276

I-277

I-278

I-279

I-280

I-281

68. The compound of claim 1 selected from the following:

I-282

I-283

I-284

I-285

I-286

I-287

I-288

I-289

I-290

I-291

I-292

I-293

I-294

I-295

I-296

I-297

I-298

I-299

I-300

I-301

I-302

I-303

I-304

I-305

I-306

I-307

I-308

I-309

I-310

I-311

I-312

I-313

I-314

I-315

I-316

I-317

I-318

I-319

I-320

I-321

I-322

I-323

I-324

I-325

I-326

I-327

I-328

I-329

I-330

I-331

I-332

I-333

I-334

I-335

I-336

I-337

I-338

I-339

I-340

I-341

I-342

I-343

I-344

I-345

I-346

I-347

69. The compound of claim 1 selected from the following:

I-348

I-349

I-350

I-351

I-352

I-353

I-354

I-355

I-356

I-357

I-358

I-359

I-360

I-361

I-362

I-363

I-364

I-365

I-366

I-367

I-368

I-369

I-370

I-371

I-372

I-373

I-374

I-375

I-376

I-377

70. A composition comprising a compound of formula I wherein the variables are as defined in claim 1 .

71. The compound of claim 31 , wherein R 1 is