Substituted pyrrolo[2,3-d]pyrimidines as inhibitors of protein kinases

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is H;

R 2 is H;

Z 1 and Z 2 , together with the carbon atom to which they are attached, form ring Q;

Z 3 is H; or

Z 1 , Z 2 , and Z 3 , together with the carbon atom to which they are attached, form a 6-14 membered saturated, partially saturated, or unsaturated bicyclic ring having 0-3 heteroatoms;

if the bond between Z 1 and C is a double bond, then Z 3 is absent;

Q is a 3-8 membered saturated or partially saturated monocyclic ring having 0-3 heteroatoms selected from nitrogen, oxygen, or sulfur, wherein said Q is optionally and independently fused to Q 1 or Q 2 ; or to both Q 1 and Q 2 ; wherein said Q is optionally substituted with 0-4 J Q groups;

Q 1 is a 3-8 membered saturated, partially saturated, or unsaturated monocyclic ring having 0-3 heteroatoms selected from nitrogen, oxygen, or sulfur, wherein said Q 1 group is optionally substituted with 0-4 J Q groups;

Q 2 is a 3-8 membered saturated, partially saturated, or unsaturated monocyclic ring having 0-3 heteroatoms selected from nitrogen, oxygen, or sulfur wherein said Q 2 group is optionally substituted with 0-4 J Q groups;

R is H, optionally substituted C 1-6 aliphatic, C 3-10 cycloaliphatic, C 6-10 aryl, 5-14 membered heteroaryl, or 5-14 membered heterocyclyl; or two R groups, on the same substituent or different substituents, together with the atom(s) to which each R group is bound, form an optionally substituted 3-14 membered saturated, partially unsaturated, or fully unsaturated monocyclic, bicyclic, or tricyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur wherein each R is optionally substituted with 0-10 J R groups;

each J Q substituent on an unsaturated carbon atom is independently selected from hydrogen, —OCF 3 , C 1-6 haloalkyl, N(R) 2 , OR, halogen, Y, —(V) n —CN, —(V) n —NO 2 , —(V) n —OH, —(V) n —(C 1-6 aliphatic), —(C 3-10 cycloaliphatic)-C(O)R, —(C 3-10 cycloaliphatic)-(C 3-12 heterocyclyl); —(V) n —(C 3-12 heterocyclyl), —(V) n —(C 6-10 aryl), —(V) n -(5-10 membered heteroaryl), —(V) n —(C 3-10 cycloaliphatic); wherein each J Q is optionally substituted with up to 10 J R groups;

each J Q substituent on a saturated carbon atom is selected from those listed above for an unsaturated carbon and also the following: ═O, ═NN(R a ) 2 , ═NNHC(O)R a , ═NNHCO 2 (C 1-4 alkyl), ═NNHSO 2 (C 1-4 alkyl), and ═NR a wherein each J Q is optionally substituted with up to 10 J R groups;

each J Q substituent on an unsaturated carbon atom is independently selected from hydrogen, Y, —(V) n —CN, —(V) n —NO 2 , —(V) n —OH, —(V) n —(C 1-6 aliphatic), —(C 3-10 cycloaliphatic)-C(O)R, —(C 3-10 cycloaliphatic)-(C 3-12 heterocyclyl); —(V) n —(C 3-12 heterocyclyl), —(V) n —(C 6-10 aryl), —(V) n -(5-10 membered heteroaryl), —(V) n —(C 3-10 cycloaliphatic); wherein each J Q is optionally substituted with up to 10 J R groups;

J R is selected from halogen, —N(R b ) 2 , SR b , OR b , oxo, C 1-4 haloalkoxy, C 1-4 haloalkyl, L, -(L) n -(C 1-6 alkyl), -(L) n -(C 3-12 heterocyclyl), -(L) n -(C 6-10 aryl), -(L) n -(5-10 membered heteroaryl), -(L) n -(C 3-10 cycloalipahtic), -(L) n -NO 2 , -(L) n -CN, -(L) n -OH, —CO 2 R b , —COR b , —OC(O)R b , —NHC(O)R b ;

L is C 1-10 alkyl wherein up to three methylene units are replaced by —NR b —, —O—, —S—, —CO 2 —, —OC(O)—, —C(O)CO—, —C(O)—, —C(O)NR b —, —C(═N—CN), —NR b CO—, —NR b C(O)O—, —SO 2 NR b —, —NR b SO 2 —, —NR b C(O)NR—, —OC(O)NR b —, —NR b SO 2 NR b —, —SO—, or —SO 2 —;

V is C 1-10 aliphatic wherein up to three methylene units are replaced by G V , wherein G V is selected from —NR—, —O—, —S—, —CO 2 —, —OC(O)—, —C(O)CO—, —C(O)—, —C(O)NR—, —C(═N—CN), —NRCO—, —NRC(O)O—, —SO 2 NR—, —NRSO 2 —, —NRC(O)NR—, —OC(O)NR—, —NRSO 2 NR—, —SO—, or —SO 2 —;

Y is C 1-10 aliphatic, wherein up to three methylene units are replaced by G Y wherein G Y is selected from —NR—, —O—, —S—, —CO 2 —, —OC(O)—, —C(O)CO—, —C(O)—, —C(O)NR—, —C(═N—CN), —NRCO—, —NRC(O)O—, —SO 2 NR—, —NRSO 2 —, —NRC(O)NR—, —OC(O)NR—, —NRSO 2 NR—, —SO—, or —SO 2 —;

R a is hydrogen or C 1-6 aliphatic group optionally substituted with 0-3 J R groups;

R b is hydrogen or an unsubstituted C 1-6 aliphatic group;

n is 0 or 1.

2. The compound according to claim 1 , wherein Z 1 and Z 2 , together with the carbon atom to which they are attached, form a compound as shown in Formula IV:

wherein

Z 11 is selected from C, N, O, or S;

Z 12 is selected from C, N, O, or S;

Q is a 3-8 membered saturated or partially saturated monocyclic ring, optionally fused to Q 1 or Q 2 ;

Q 1 and Q 2 are each independently a 3-8 membered saturated, unsaturated, or partially saturated monocyclic rings;

Q, Q 1 and Q 2 each independently contain up to three heteroatoms selected from O, N, or S;

m is 0-4; and is independently selected for Q, Q 1 and Q 2 ; and

Z 3 is H; or if the bond between C and Z 11 is a double bond, then Z 3 is absent.

3. The compound according to claim 1 , wherein Q or Q-Q 1 is selected from:

wherein

both R 7 and J Q are each independently selected from hydrogen, Y, —(V) n —CN, —(V) n —NO 2 , —(V) n —OH, —(V) n —(C 1-6 aliphatic), —(V) n —(C 3-12 heterocyclyl), —(V) n —(C 6-10 aryl), —(V) n -(5-10 membered heteroaryl), —(V) n —(C 3-10 cycloaliphatic) and —(C 3-10 cycloaliphatic)-(C 3-12 heterocyclyl);

each, m is independently 0-2; and

each R 7 and J Q is optionally and independently substituted with 0-10 J R groups.

4. The compound according to claim 1 having formula VII:

5. A compound selected from:

1

2

3

9

10

11

13

15

16

17

19

20

21

26

27

6. The composition of claim 5 , additionally comprising a therapeutic agent selected from a chemotherapeutic or anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory or immunosuppressive agent, a neurotrophic factor, an agent for treating cardiovascular disease, an agent for treating diabetes, or an agent for treating immunodeficiency disorders.