HETEROARYL COMPOUNDS AND USES THEREOF

1 . A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

Ring A is a saturated 4-8 membered monocyclic or bridged heterocyclic ring having one —N(R 1 )—, a saturated 7-11 membered spirofused heterocyclic ring having one —N(R 1 )—, or a saturated 8-10 membered bicyclic heterocyclic ring having one —N(R 1 )—, wherein Ring A is substituted with 0-3 R v groups;

R 1 is -L-Y, wherein:

L is an optionally substituted bivalent C 2-8 unsaturated, straight or branched, hydrocarbon chain, wherein one, two, or three methylene units of L are optionally and independently replaced by cyclopropylene, —N(R)—, —N(R)C(O)—, —C(O)N(R)—, —N(R)SO 2 —, —SO 2 N(R)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO 2 —, —C(═S)—, —C(═NR)—, —N═N—, or —C(═N 2 )—; and

Y is hydrogen, halogen, —CN, C 1-6 aliphatic optionally substituted with oxo, halogen, or CN, or a 3-10 membered monocyclic or bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein said ring is substituted with 1-4 groups independently selected from -Q-Z, oxo, —NO 2 , halogen, —CN, and C 1-6 aliphatic, wherein:

Q is a covalent bond or a bivalent C 1-6 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —N(R)—, —S—, —O—, —C(O)—, —SO—, or —SO 2 —; and

Z is hydrogen or C 1-6 aliphatic optionally substituted with oxo, halogen, or CN;

Ring B is a saturated 5-7-membered heterocyclo ring having 1-2 nitrogen atoms, wherein Ring B is substituted with 0-5 R x groups;

W is —N(R 2 )CH 2 — or —NH—;

R 2 is selected from hydrogen, C 1-6 aliphatic or —C(O)R;

R 3 and R 4 are each independently selected from hydrogen or halogen;

each R group is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R y is hydrogen, halogen, —CF 3 , or C 1-4 aliphatic;

each R x is independently oxo, halogen, —OR, —N(R) 2 , —S(O) x R, —N(R)(CH 2 ) q N(R) 2 , —N(R)(CH 2 ) q OR, —O(CH 2 ) q OR, —O(CH 2 ) q N(R) 2 , an optionally substituted C 2-6 saturated, straight or branched, hydrocarbon chain wherein one or two methylene units are independently replaced by —O—, —N(R)— or —S(O) x —, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each R v is independently selected from halogen or C 1-6 aliphatic;

q is 1 or 2; and

each x is 0, 1 or 2.

2 . The compound according to claim 1 , wherein Ring A is a saturated 4-8 membered monocyclic or bridged heterocyclic ring having one —N(R 1 )—.

3 . The compound according to claim 1 , wherein Ring A is a saturated 7-11 membered spirofused heterocyclic ring having one —N(R 1 )—.

4 . The compound according to claim 2 , wherein the compound is of formula II-a, II-b, II-c, II-d, II-e, II-f, II-g, II-h, II-i, II-j, II-k or II-l:

or a pharmaceutically acceptable salt thereof.

5 . The compound according to claim 4 , wherein the compound is of formula II-b-i, II-b-ii, II-c-i, II-c-ii, II-e-i, II-e-ii, II-f-i, II-f-ii, II-g-i, II-g-ii, II-h-i or II-h-ii:

or a pharmaceutically acceptable salt thereof.

6 . The compound according to claim 1 , wherein Ring B is a 5-membered heterocyclo ring.

7 . The compound according to claim 6 , wherein Ring B is pyrrolidino ring.

8 . The compound according to claim 1 , wherein Ring B is a 6-membered heterocyclo ring.

9 . The compound according to claim 8 , wherein Ring B is a piperidino ring.

10 . The compound according to claim 1 , wherein the compound is of formula III-a, III-b, III-c, III-d, III-e, III-f, III-g or III-h:

or a pharmaceutically acceptable salt thereof.

11 . The compound according to claim 10 , wherein Ring A is selected from

12 . The compound according to claim 3 , wherein Ring A is substituted with 0-3 R v groups and is selected from azaspiro[2.4]heptane, azaspiro[3.3]heptane, azaspiro[2.5]octane, azaspiro[3.4]octane, azaspiro[3.5]nonane, azaspiro[4.4]nonane, azaspiro[4.5]decane, azaspiro[3.7]undecane, azaspiro[4.6]undecane, azaspiro[5.5]undecane.

13 . The compound according to claim 12 , wherein Ring A is substituted with 0-3 R v groups and is selected from:

14 . The compound according to claim 1 , wherein R y is halogen.

15 . The compound according to claim 14 , wherein R y is fluoro.

16 . The compound according to claim 1 , wherein R 2 is hydrogen.

17 . The compound according to claim 1 , wherein R 1 is -L-Y, wherein:

L is an optionally substituted bivalent C 2-8 straight or branched, hydrocarbon chain wherein L has at least one double bond and one or two methylene units of L are optionally and independently replaced by —N(R)C(O)—, —C(O)NR—, —N(R)SO 2 —, —SO 2 N(R)—, —S—, —S(O)—, —SO 2 —, —OC(O)—, —C(O)O—, cyclopropylene, —O—, —N(R)—, or —C(O)—.

18 . The compound according to claim 17 , wherein:

L is an optionally substituted bivalent C 2-8 straight or branched, hydrocarbon chain wherein L has at least one double bond and at least one methylene unit of L is replaced by —C(O)—, —N(R)C(O)—, —C(O)NR—, —N(R)SO 2 —, —SO 2 N(R)—, —S—, —S(O)—, —SO 2 —, —OC(O)—, or —C(O)O—, and one additional methylene unit of L is optionally replaced by cyclopropylene, —O—, —N(R)—, or —C(O)—; and

Y is hydrogen, halogen, —CN or C 1-6 aliphatic optionally substituted with oxo, halogen, NO 2 , or CN.

19 . The compound according to claim 18 , wherein L is an optionally substituted bivalent C 2-8 straight or branched, hydrocarbon chain wherein L has at least one double bond and one methylene unit of L is replaced by —C(O)—, and one additional methylene unit of L is optionally replaced by cyclopropylene, —O—, —N(R)—, or —C(O)—.

20 . The compound according to claim 18 , wherein L is an optionally substituted bivalent C 2-8 straight or branched, hydrocarbon chain wherein L has at least one double bond and one methylene unit of L is replaced by —SO 2 —

21 . The compound according to claim 18 , wherein L is substituted with —OH, —CN or halogen.

22 . The compound according to claim 1 , wherein L is —C(O)CH═CH—, —C(O)CH═C(F)—, —C(O)CH═C(CN)—, —CH(OH)CH═CH—, —CH(OH)C(F)═CH—, —CH(OH)C(CN)═CH—, —CH(OH)CH═C(F)—, or —CH(OH)CH═C(CN)—.

23 . The compound according to claim 1 , wherein R 1 is -L-Y, wherein:

L is an optionally substituted bivalent C 2-8 straight or branched, hydrocarbon chain wherein L has at least one triple bond and one or two additional methylene units of L are optionally and independently replaced by —C(O)—, —O—, N(R)—, —N(R)C(O)—, —C(O)NR—, —N(R)SO 2 —, —SO 2 N(R)—, —S—, —S(O)—, —SO 2 —, —OC(O)—, or —C(O)O—.

24 . The compound according to claim 23 , wherein Y is hydrogen or C 1-6 aliphatic optionally substituted with oxo, halogen, NO 2 , or CN.

25 . The compound according to claim 24 , wherein L is —C(O)C≡C—.

26 . The compound according to claim 1 , wherein R 1 is selected from:

27 . The compound according to claim 1 , wherein W is —NH—.

28 . The compound according to claim 1 , wherein R v is halogen.

29 . The compound according to claim 28 , wherein R v is fluoro.

30 . The compound according to claim 1 , wherein R x is an optionally substituted C 1-6 aliphatic.

31 . The compound according to claim 30 , wherein R x is —CH 3 , —CH(CH 3 ) 2 , —C(CH 3 ) 3 , or —CH 2 C(CH3) 3 .

32 . The compound according to claim 30 , wherein the C 1-6 aliphatic is substituted with oxo.

33 . The compound according to claim 32 , wherein R x is —C(O)CH 3 or —CH 2 C(O)NH 2 .

34 . The compound according to claim 30 , wherein R x is selected from

—CH 2 CH 2 F, —CH 2 CH 2 OH and —CH 2 CH 2 OCH 3 ,

wherein each R  is selected from hydrogen and C 1-6 aliphatic optionally substituted with halogen.

35 . The compound according to claim 1 , wherein R x is an optionally substituted 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

36 . The compound according to claim 35 , wherein R x is selected from

wherein each R † is selected from hydrogen and C 1-6 aliphatic optionally substituted with halogen.

37 . The compound according to claim 1 , wherein R x is an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring.

38 . The compound according to claim 37 , wherein R x is selected from

39 . The compound according to claim 1 , wherein R x is optionally substituted phenyl.

40 . The compound according to claim 39 , wherein R x is

41 . A method of inhibiting a B cell receptor, comprising contacting a cell with a compound according to claim 1 .

42 . A method of treating or lessening the severity of a B cell-mediated disorder, comprising administering to a patient in need thereof a compound according to claim 1 .

43 . A method of inhibiting a T cell receptor, comprising contacting a cell with a compound according to claim 1 .

44 . A method of treating or lessening the severity of a T cell-mediated disorder, comprising administering to a patient in need thereof a compound according to claim 1 .