Substituted pyrrolidines as SYK inhibitors

1. A compound of Formula I:

wherein:

X 1 is CH or N;

X 2 is CR 1a , NR 1b or S;

X 3 is C or N;

wherein,

X 1 , X 2 and X 3 are arranged in such a way to for a heteroaromatic ring system, and

R 1a is hydrogen, halo, haloalkyl, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkoxy, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 6-12 aryl, C 2-12 heteroaryl, or —N(R 20 )(R 22 ),

wherein the C 1-6 alkyl, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 6-12 aryl, or C 2-12 heteroaryl moieties may be optionally substituted with one, two, or three substituents independently selected from fluoro, CH 2 F, CHF 2 , CF 3 , C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkoxy, C 3-12 cycloalkyl, and —N(R 20 )(R 22 ),

R 1b is hydrogen, haloalkyl, C 1-6 alkyl, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 6-12 aryl, or C 2-12 heteroaryl,

wherein the C 1-6 alkyl, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 6-12 aryl, or C 2-12 heteroaryl moieties may be optionally substituted with one, two, or three substituents independently selected from fluoro, CH 2 F, CHF 2 CF 3 , and C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkoxy, C 3-12 cycloalkyl, and —N(R 20 )(R 22 ),

provided that either (a) or (b) applies:

a) when X 3 is N then X 2 is CR 1a , or

b) when X 2 is S then X 1 is CH and X 3 is C;

Y is O or NH;

R 2 is hydrogen, C 1-6 alkyl, C 3-12 cycloalkyl, C 2-12 heterocyclyl, C 1-6 alkoxy, or —N(R 20 )(R 22 );

wherein the C 1-6 alkyl, C 3-12 cycloalkyl, C 2-12 heterocyclyl, or C 1-6 alkoxy moieties may be optionally substituted with one, two, or three substituents independently selected from fluoro, CH 2 F, CHF 2 , CF 3 , C 1-6 alkyl, and C 1-6 alkoxy;

each R 3 and R 4 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, and C 2-6 alkenyl,

wherein the C 1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, and C 2-6 alkenyl moieties may be optionally substituted with one, two, or three substituents independently selected from halogen, C 1-6 alkyl, C 3-6 cycloalkyl, C 6-12 aryl, C 2-8 heterocyclyl, C 2-12 heteroaryl, —OR 20 , or —N(R 20 )(R 22 );

R 5 is C 6-12 aryl, C 3-12 cycloalkyl, C 2-8 heterocyclyl having one, two, three, or four heteroatoms independently selected from O, N, and S, or C 2-12 heteroaryl having one, two, three, or four heteroatoms independently selected from O, N, and S;

wherein the C 6-12 aryl, C 3-12 cycloalkyl, C 2-8 heterocyclyl, and C 2-12 heteroaryl moiety may be optionally substituted with one, two, or three substituents independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkynyl, C 1-6 alkoxy, halo, —NO 2 , CH 2 F, CF 3 , CHF 2 , —OCF 3 , C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, C 2-12 heteroaryl, —S(O) 2 R 20 ,—S(O) 2 —N(R 20 )(R 22 ), —N(R 20 )(R 22 ), —N(R 20 )—S(O) 2 —R 20 , —N(R 20 )—C(O)—R 22 , —C(O)—R 20 , —C(O)—OR 20 , —C(O)—N(R 20 )(R 22 ), —CN, oxo, and —O—R 20 ;

wherein the C 1-6 alkyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, or C 2-12 heteroaryl moiety may be optionally further substituted with one, two, or three substituents independently selected from the group consisting of halo, —NO 2 , CH 2 F, —CF 3 , CHF 2 , —OCF 3 , C 1-6 alkyl, C 3-6 cycloalkyl, C 6-12 aryl, C 2-8 heterocyclyl, C 2-6 heteroaryl, —N(R 20 )(R 22 ), —C(O)—R 20 , —C(O)—OR 20 , —C(O)—N(R 20 )(R 22 ), —CN, —S(O) 2 R 20 , —S(O) 2 —N(R 20 )(R 22 ), —S(O) 2 —R 20 —N(R 20 )(R 22 ), oxo, and —O—R 20 ;

wherein the C 1-6 alkyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 2-6 heteroaryl may be further optionally substituted with one, two, or three substituents independently selected from the group consisting of C 1-6 alkyl, C 3-6 cycloalkyl, C 6-12 aryl, C 2-6 heteroaryl, C 2-8 heterocyclyl, halo, —NO 2 , CH 2 F, CHF 2 , —CF 3 , —OCF 3 , —N(R 20 )(R 22 ), —C(O)—R 20 , —C(O)—OR 20 , —C(O)—N(R 20 )(R 22 ), —CN, —S(O) 2 —R 20 , S(O) 2 —N(R 20 )(R 22 ), —S(O) 2 —R 20 —N(R 20 )(R 22 ), oxo, and —O—R 20 ; and

each R 20 and R 22 is independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, or C 2-12 heteroaryl;

wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 2-12 heteroaryl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of hydroxy, halo, C 1-6 alkyl, acylamino, oxo, —NO 2 , —S(O) 2 R 26 , —CN, C 1-6 alkoxy, C 3-6 cycloalkoxy, CH 2 F, —CF 3 , CHF 2 , —OCF 3 , —OCH 2 CF 3 , —C(O)—NH 2 , C 6-12 aryl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, and C 2-6 heteroaryl; and

wherein R 26 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, C 2-6 heteroaryl, acylamino, NH 2 , CH 2 F, —CF 3 , or CHF 2 ;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

2. The compound of claim 1 represented by Formula II

wherein:

Y is O;

R 1a is hydrogen, cyano, chloro, methyl, ethyl, propyl, or butyl;

R 2 is hydrogen or methyl;

R 3 is methyl, ethyl, propyl, or butyl;

R 4 is hydrogen; and

R 5 is phenyl or pyrazoiyl,

wherein the phenyl and pyrazolyl moieties may be optionally substituted with one or two substituents independently selected from the group consisting of fluoro, . . . piperazinyl, and morpholino;

wherein the piperazinyl moiety may be optionally substituted with one substituent selected from the group consisting of C 2-5 heterocyclyl, —S(O) 2 -alkyl, —S(O) 2 —C 3-6 cycloalkyl, —S(O) 2 —C 2-8 heterocyclyl, and —C(O)—C 1-6 alkyl; or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

3. The compound of claim 2 ,

wherein:

Y is O;

R 1a is hydrogen, methyl, cyano, bromo or chloro;

R 2 is hydrogen or methyl;

R 3 is methyl;

R 4 is hydrogen;

R 5 is:

R 27 is H, C 1-4 alkyl, —CH 2 F, CHF 2 , or CF 3 ;

and (i) R 28 , R 29 and R 30 are each independently hydrogen, fluoro, cyano, or —OC 1-3 alkyl;

or (ii) R 28 and R 29 are each independently hydrogen or —OC 1-3 alkyl, and R 30 is morpholino or piperazinyl, wherein the piperazinyl moiety may be optionally substituted with one substituent selected from the group consisting of —S(O) 2 H, —S(O) 2 —C 1-3 alkyl, —S(O) 2 —C 3-6 cycloalkyl, —S(O) 2 —C 2-8 heterocyclyl, C 1-4 alkyl, —C(O)—C 1-4 alkyl, C 3-6 cycloalkyl, and C 2-5 heterocyclyl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

4. The compound of claim 2 ,

wherein:

Y is O;

R 1a is hydrogen, methyl or chloro;

R 2 is hydrogen or methyl;

R 3 is methyl;

R 4 is hydrogen;

R 5 is:

and (i) R 28 , R 29 and R 30 are each independently hydrogen or methoxy;

or (ii) R 28 and R 29 are hydrogen, and R 30 is morpholino;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

5. The compound of claim 1 represented by Formula IIa,

wherein:

R 1a is hydrogen, methyl or cyano;

R 2 is hydrogen or methyl;

R 3 is hydrogen or methoxy; and

R 1d is hydrogen, C 1-4 alkyl, —C(O)—C 1-4 alkyl, —S(O) 2 H, —S(O) 2 —C 1-3 alkyl, —S(O) 2 —C 3-6 cycloalkyl, —S(O) 2 —C 2-8 heterocyclyl, C 3-6 cycloalkyl, or C 2-6 heterocyclyl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

6. The compound of claim 1 represented by Formula III:

wherein:

Y is O;

R 1a is hydrogen, halo, haloalkyl, cyano, C 1-6 alkyl, or C 3-6 cycloalkyl;

R 2 is hydrogen;

R 3 is C 1-6 alkyl;

R 4 is hydrogen; and

R 5 is phenyl, pyridinyl, pyrazolyl, indazolyl, thieno[3,2-c]pyrazolyl, pyimidinyl, imidazolyl, or indolin-2-onyl;

wherein the phenyl, . . . and indolin-2-onyl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, —S(O) 2 R 20 , —S(O) 2 —NR 20 R 22 , —NO 2 , —N(R 20 )(R 22 ), —C(O)—OR 20 , —CN, oxo, and —O—R 20 ;

wherein the alkyl, alkoxy, alkynyl, cycloalkyl, or heterocyclyl moieties are further optionally substituted with zero, one, two or three substituents independently selected from the group consisting, of halo, C 1-6 alkyl, C 3-6 cycloalkyl, C 6-12 aryl, C 2-8 heterocyclyl, C 2-6 heteroaryl, —NO 2 , —S(O) 2 R 20 , —N(R 20 )(R 22 ), —C(O)—R 20 , —C(O)—OR 20 , —C(O)—N(R 20 )(R 22 ), —CN, and —O—R 20 ; and

R 20 and R 22 are each independently hydrogen, . . . or C 2-6 heteroaryl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

7. The compound of claim 6 ,

wherein:

Y is O;

R 1a is hydrogen, cyano, chloro, methyl, ethyl, propyl, butyl, or C 3-6 cycloalkyl;

R 2 is hydrogen;

R 3 is methyl;

R 4 is hydrogen; and

R 5 is phenyl, pyridinyl or pyrazolyl;

wherein the phenyl, pyridinyl and pyrazolyl moieties may be optionally substituted with one, two or three substituents independently selected from the group consisting of methyl, ethyl, propyl, butyl, cyano, methoxy, ethoxy, propoxy, morpholinyl, piperazinyl, oxetanyl, C 1-4 fluoroalkyl, cyclopropyl and cyclobutyl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

8. The compound of claim 6 ,

wherein:

Y is O;

R 1a is hydrogen, methyl, chloro or cyclopropyl;

R 2 is hydrogen or methyl;

R 3 is methyl;

R 4 is hydrogen;

R 5 is:

R 27 is

(i) R 28 , R 29 and R 30 are each independently hydrogen or —OC 1-3 alkyl;

or (ii) R 28 and R 29 are each independently hydrogen or —OC 1-3 alkyl, and R 30 is morpholino or piperazinyl;

wherein the piperazinyl moiety may be optionally substituted with one substituent selected from the group consisting of —S(O) 2 H, —S(O) 2 —C 1-3 alkyl, —S(O) 2 —C 3-6 cycloalkyl, —S(O) 2 —C 2-8 heterocyclyl, C 1-4 alkyl, —C(O)—C 1-4 alkyl, C 3-6 cycloalkyl, and C 2-6 heterocyclyl;

(iii) R 31 , R 32 and R 33 are each independently hydrogen, C 1-3 alkyl, or —OC 1-3 alkyl;

or (iv) R 31 and R 32 are each independently hydrogen or —OC 1-3 alkyl, and R 33 is morpholino or piperazinyl;

wherein the piperazinyl moiety may be optionally substituted with one substituent selected from the group consisting of —S(O) 2 H, —S(O) 2 —C 1-3 alkyl, —S(O) 2 —C 3-6 cycloalkyl, —S(O) 2 —C 2-8 heterocyclyl, C 1-4 alkyl, —C(O)—C 1-4 alkyl, C 3-6 cycloalkyl, and C 2-6 heterocyclyl; and

R Y is hydrogen, C 1-4 alkyl, or —OC 1-3 alkyl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

9. The compound of claim 1 represented by Formula IIIa,

wherein:

R 1a is hydrogen, cyano, methyl, chloro, or cyclopropyl;

R 2 is hydrogen or methyl;

X 5 is —CH— or nitrogen;

R 1e is hydrogen or methoxy; and

R 1f is hydrogen, —S(O) 2 H, —S(O) 2 —C 1-3 alkyl, C 1-4 alkyl, C 3-6 cycloalkyl, or C 2-6 heterocyclyl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

10. The compound of claim 1 represented by Formula IV,

wherein:

Y is O;

R 1b is hydrogen, C 1-4 alkyl, or C 3-6 cycloalkyl;

wherein the C 1-4 alkyl and C 3-6 cycloalkyl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of fluoro and C 1-6 alkyl;

R 2 is hydrogen or methyl;

R 3 is methyl, ethyl, propyl, or butyl;

R 4 is hydrogen; and

R 5 is selected from the group consisting of phenyl, pyridinyl, pyrazolyl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridinyl, benzomorpholinyl, thiazolyl, indolinyl, 1,3,4-thiadiazolyl, pyrimidinyl, imidazolyl, pyrazinyl, pyridazinyl, pyrrolo[2,3-b]pyridin-2(3H)-onyl, pyrido[2,3-b][1,4]oxazin-2(3H)-onyl, pyrido[3,2-b][1,4]oxazin-3(4H)-onyl, 3,4-dihydropyrido[3,2-b][1,4]oxazinyl, benzimidazolyl, and 2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazinyl;

wherein the R 5 moiety may be optionally substituted with one, two, or three substituents independently selected from the group consisting of C 1-6 alkyl, . . . difluoropropyl, . . . and cyclobutyl;

wherein the C 1-6 alkyl moiety may be optionally substituted with one hydroxy;

wherein the R 5 phenyl moiety may be optionally substituted with one substituent selected from the group consisting of morpholino and a group of the formula:

wherein the R 5 pyridazinyl moiety may be optionally substituted with one substituent selected from the group consisting of morpholino and a group of the formula:

wherein the R 5 pyridinyl moiety may be optionally substituted with one substituent selected from the group consisting of a) piperazinyl, optionally substituted with one substituent selected from the group consisting of —C(O)—C 1-3 alkyl, . . . and —S(O) 2 —C 2-8 heterocyclyl, and b) piperidinyl, optionally substituted with one substituent selected from the group consisting of C 2-5 heterocyclyl and 6-oxa-3-azabicyclo[3.1.1]heptanyl;

wherein the R 5 pyrazolyl moiety may be optionally substituted with one, two or three substituents independently selected from the group consisting of a) C 2-5 heterocyclyl, b) C 1-6 alkyl, optionally substituted with one or two substituents independently selected from the group consisting of OH, . . . and —C(O)N(C 1-3 alkyl) 2 , and c) pyridinyl; and

wherein the R 5 thiazolyl moiety may be optionally substituted with one substituent selected from the group consisting of a) morpholino, b) C 2-5 heterocyclyl, and c) C 1-6 alkyl, optionally substituted with one or two substituents independently selected from the group consisting of OH, . . . and —C(O)N(C 1-3 alkyl) 2 ;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

11. The compound of claim 1 represented by Formula V,

wherein:

Y is O;

R 2 is hydrogen or methyl;

R 3 is hydrogen, C 1-6 alkyl, or C 2-3 alkenyl;

R 4 is hydrogen;

R 5 is selected from the group consisting of phenyl, pyridinyl, pyrazolyl, pyrazinyl, pyridazinyl, thiazolyl, benzothiazolyl, benzomorpholinyl, thieno[3,2-c]pyrazolyl, indazolyl, indolin-2-onyl, quinazolin-4(3H)-onyl, pyrrolo[2,3-b]pyridin-2(3H)-onyl, pyrrolo[3,2-c]pyridin-2(3H)-onyl, 3,4-dihydroquinolin-2(1H)onyl, pyrazolo[3,4-b]pyridinyl, 2,3-dihydrobenzofuranyl, 3,4-dihydroquinolin-2(1H)-onyl and 3,4-dihydropyrido[3,2-b][1,4]oxazinyl;

wherein the R 5 moiety may be optionally substituted with one, two, or three substituents independently selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, and C 2-8 heterocyclyl;

wherein the C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, and C 2-8 heterocyclyl moieties may be independently and optionally substituted with one substituent selected from the group consisting of halo, C 3-8 cycloalkyl, C 2-8 heterocyclyl, —C(O)O—R 20 , —C(O)R 20 , —NO 2 , —N(R 20 )(R 22 ), —S(O) 2 R 20 , —S(O) 2 —N(R 20 )(R 22 ) —C(O)—N(R 20 )(R 22 ), oxo, —CN, and —O—R 20 ; and

wherein each R 20 and R 22 is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 2-6 heteroaryl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

12. The compound of claim 1 represented by Formula VI,

wherein;

Y is O;

R 1b is hydrogen, halo, C 1-6 alkyl, C 3-6 cycloalkyl, or C 2-8 heterocyclyl;

wherein the C 1-6 alkyl, C 3-6 cycloalkyl and C 2-8 heterocyclyl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of fluoro and C 1-6 alkyl;

R 3 is hydrogen, C 1-6 alkyl, C 2-3 alkenyl, or C 3-6 cycloalkyl;

wherein the C 1-6 alkyl and C 3-6 cycloalkyl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halo and C 1-6 alkyl;

R 4 is hydrogen; and

R 5 is phenyl, pyridinyl, pyrazolyl, thiazolyl, indazolyl, cyclohexenyl, thienopyrazolyl, or pyrazolopyridinyl;

wherein the R 5 moiety may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 2-8 heterocyclyl, —C(O)O—R 20 , —C(O)R 20 , —NO 2 , —N(R 20 )(R 22 ), —S(O) 2 R 20 , —S(O) 2 —N(R 20 )(R 22 ), —C(O)—N(R 20 )(R 22 ), —CN, oxo, and —O—R 20 ;

wherein the C 3-6 cycloalkyl and C 2-8 heterocyclyl moieties may be independently and optionally substituted with one substituent selected from the group consisting of C 3-8 cycloalkyl, C 2-8 heterocyclyl, —C(O)O—R 20 , —C(O)R 20 , —NO 2 , —N(R 20 )(R 22 ), —S(O) 2 R 20 , —S(O) 2 —N(R 20 )(R 22 ), —C(O)—N(R 20 )(R 22 ), —CN, oxo, and —O—R 20 ;

wherein each R 20 and R 22 is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 2-6 heteroaryl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

13. The compound of claim 1 wherein R 5 is phenyl, pyridinyl, pyrazolyl, indazolyl, benzothiazolyl, dihydrobenzoxazinyl, benzodioxolyl, thiazolyl, pyrazolopyridinyl, cyclohexenyl, tetrahydrobenzoxazepanyl, and thienopyrazolyl;

wherein the phenyl, pyridinyl, pyrazolyl, indazolyl, benzothiozolyl, dihydrobenzoxazinyl, benzodioxolyl, thiazolyl, pyrazolopyridinyl, cyclohexenyl, tetrahydrobenzoxazepanyl, and thienopyrazolyl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkynyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, C 2-6 heteroaryl, —S(O) 2 R 20 , —S(O) 2 —N(R 20 )(R 22 ), —N(R 20 )(R 22 ), —NO 2 , —N(R 20 )—S(O) 2 R 20 , —N(R 20 )—C(O)—R 22 , —C(O)—R 20 , —C(O)—OR 20 , —C(O)—N(R 20 )(R 22 ), —CN, oxo, and —O—R 20 ;

wherein the C 1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 2-6 heteroaryl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, C 1-6 alkyl, C 3-6 cycloalkyl, C 6-12 aryl, C 2-8 heterocyclyl, C 2-6 heteroaryl, —S(O) 2 —R 20 , —S(O) 2 —N(R 20 )(R 22 ), —NO 2 , —N(R 20 )(R 22 ), —C(O)—R 20 , —C(O)—OR 20 , —C(O)—N(R 20 )(R 22 ), —CN, oxo, and —O—R 20 ;

wherein each R 20 and R 22 is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 2-6 heteroaryl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

14. The compound of claim 1 , wherein R 5 is phenyl, pyridinyl, pyrazolyl, indazolyl, benzothiazolyl, dihydrobenzoxazinyl, benzodioxolyl, thiazolyl, pyrazolopyridinyl, cyclohexenyl, tetrahydrobenzoxazepanyl, and thienopyrazolyl;

wherein the phenyl, pyridinyl, pyrazolyl, indazolyl, benzothiazolyl, dihydrobenzoxazinyl, benzodioxolyl, thiazolyl, pyrazolopyridinyl, cyclohexenyl, tetrahydrobenzoxazepanyl, and thienopyrazolyl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, CH 2 F, —CF 3 , CHF 2 , C 1-6 alkyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, —S(O) 2 R 20 , —S(O) 2 —NR 20 R 22 , —N(R 20 )(R 22 ), —C(O)—OR 20 , —CN, oxo, and —O—R 20 ;

wherein the C 1-6 alkyl, C 3-8 cycloalkyl, and C 2-8 heterocyclyl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, CH 2 F, —CF 3 , CHF 2 , C 1-6 alkyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, —N(R 20 )(R 22 ), —C(O)—R 20 , —C(O)—OR 20 , —C(O)—N(R 20 )(R 22 ), —CN, —O—R 20 , —S(O) 2 R 20 , —S(O) 2 —NR 20 R 22 , and oxo;

wherein each R 20 and R 22 is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 2-6 heteroaryl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

15. The compound of claim 1 , wherein:

Y is O;

R 1a is hydrogen, halo, haloalkyl, cyano, C 1-6 alkyl, C 3-6 cycloalkyl, —CH 2 —C 3-6 cycloalkyl, or C 2-5 heterocyclyl;

R 2 is hydrogen or C 1-6 alkyl, wherein the C 1-6 alkyl group is substituted by 0, 1, 2, or 3 fluorine atoms or 0 or 1 C 1-6 alkoxy substituents;

R 3 is H, C 1-6 alkyl or C 2-3 alkenyl, wherein the C 1-6 alkyl group is substituted by 0, 1, 2, or 3 fluorine atoms or 0 or 1 substituents selected from hydroxy or C 1-6 alkoxy;

R 4 is hydrogen; and

R 5 is selected from the group consisting of phenyl, pyrazolyl, pyridinyl, pyrazolo[1,5-a]pyridinyl, benzo[d][1,3]dioxolyl, benzomorpholinyl, thiazolyl, cyclohex-1-enyl, pyridin-2(1H)-onyl, dihydrobenzo[f][1,4]oxazepin-5(2H)-onyl, benzothiazolyl, thieno[3,2-c]pyrazolyl, indazolyl, pyrimidinyl, imidazolyl, indolinyl, pyrazinyl, pyridazinyl, pyrido[3,2-b][1,4]oxazinyl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridinyl, quinazolin-4(3H)-onyl, pyrrolo[2,3-b]pyridin-2(3H)-onyl, pyrrolo[3,2-c]pyridin-2(3H)-onyl, 3,4-dihydroquinolin-2(1H)-onyl, indolin-2-onyl, pyrazolo[3,4-b]pyridinyl, 2,3-dihydrobenzofuranyl, 2H-benzo[b][1,4]oxazin-3(4H)-onyl, 3,4-dihydroquinolin-2(1H)-onyl, pyrido[3,2-b][1,4]oxazin-3(4H)-onyl, benzimidazolyl, imidazo[1,2-a]pyridinyl, isoindolin-1-onyl, benzomorpholin-3-onyl, benzomorpholin-2-onyl, benzimidazolin-2-onyl, 2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazinyl, pyrido[2,3-b][1,4]oxazin-2(3H)-onyl, spiro[azetidin-3,3′-indolin]-2′-onyl, benzo[d][1,3]oxazin-2(4H)-onyl, spiro[indolin-3,4′piperidin]-2-onyl, 3,4-dihydrospiro[benzo[b][1,4]oxazin-2,1′-cyclopropan]yl, indolyl, benzoxazolin-2-onyl, pyrrolo[3,2-b]pyridin-2(3H)-onyl, thiophenyl, 3,4-dihydropyrido[3,2-b][1,4]oxazinyl, 1,3,4-thiadiazolyl, indolinyl, isothiazolyl, 1,2,3-triazolyl and thieno[2,3-c]pyridinyl;

wherein each of the R 5 moieties may be independently, optionally substituted with one, two or three substituents independently selected from the group consisting of halo, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkynyl, C 3-8 cycloalkyl, C 2-8 heterocyclyl, —S(O) 2 R 20 , —S(O) 2 —NR 20 R 22 , —NO 2 , —N(R 20 )(R 22 ), —C(O)—OR 20 , —CN, oxo, and —O—R 20 ;

wherein the C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 3-8 cycloalkyl, and C 2-8 heterocyclyl moieties may be optionally substituted with one, two, or three substituents independently selected from the group consisting of halo, CN, C 1-6 alkyl, C 3-6 cycloalkyl, C 6-12 aryl, C 2-8 heterocyclyl, C 2-6 heteroaryl, —S(O) 2 R 20 , —NO 2 , —N(R 20 )(R 22 ), —C(O)—R 20 , —C(O)—OR 20 , —C(O)—N(R 20 )(R 22 ), —CN, oxo, and —O—R 20 ; and

wherein each R 20 and R 22 is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 2-8 heterocyclyl, C 6-12 aryl, and C 2-6 heteroaryl;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

16. The compound of claim 1 , selected from the group consisting of:

(R)-4-((R)-1((6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(3,4-dimethoxyphenyl)-3-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-methyl-6-(4-morpholinophenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-chloro-6-(3,4dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(3,4-dimethoxyphenyl)-2-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(1-(tert-butyl)-1H-pyrazol-4yl)-3-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1((6-(3,4-dimethoxyphenyl)-3-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(1-(tert-butyl)-1H-pyrazol-4-yl)-3-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)4-((R)-1-((3-methyl-6-(4-morpholinophenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-chloro-6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(3,4-dimethoxyphenyl)-2-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-methyl-6-(4-morpholinophenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-methylpyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-chloro-6-(3,4dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-chloro-6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-2-methylpyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-2-methylprazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-bromo-6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-bromo-6-(3,4-dimethoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yloxy)ethyl)pyrrolidin-2-one;

4-(4-(4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazin-6-yl)phenyl)piperazine-1-carboxylate;

(R)-4-((R)-1-((6-(4-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(4-(4-acetylpiperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(4-(4-(methylsulfonyl)piperazin1-yl)phenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

tert-butyl 4-(2-methoxy-4-(4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazin-6-yl)phenyl)piperazine-1-carboxylate;

(R)-4-((R)-1-((6-(3-methoxy-4-(piperazin-1-yl)phenyl)prazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(4-(4-acetylpiperazin-1-yl)-3-methoxyphenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(3-methoxy-4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

tert-butyl 4-(4(3-methyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazin-6-yl)phenyl)piperazine-1-carboxylate;

(R)-4-((R)-1-((3-methyl-6-(4-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(4-(4-acetylpiperazin-1-yl)phenyl)-3methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-methyl-6-(4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

tert-butyl 4-(2-methoxy-4-(3-methyl-4((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazin-6-yl)phenyl)piperazine-1-carboxylate;

(R)-4-((R)-1-((6-(3-methoxy-4-(piperazin-1-yl)phenyl)-3-methylprazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6(4(4-acetylpiperazin-1-yl)-3-methoxyphenyl)-3-methylprazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(3-methoxy-4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-3-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(3-methoxy-4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-3-methylpyrazolo[1,5-a]pyrazin-4-yl)oxy)ethyl)pyrrolidin-2-one;

6-chloro-4-((R)-1-((R)-1-((R)-1-(4-methoxyphenyl)ethyl)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile;

6-(3,4-dimethoxyphenyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile;

6-(4-(4-acetylpiperazin-1-yl)phenyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile;

6-(4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile;

6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-]pyrazine-3-carbonitrile;

(R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-3-ethyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((S)-1-(6-(3,4-dimethoxyphenyl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-cyclopropyl-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4((R)-1-(3-methyl-6-(3,4,5-trimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((6-(3,4-dimethoxyphenyl)-3methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)methyl)pyrrolidin-2-one;

(R)-4-((R)-2-cyclopropyl-1-(6-(3,4-dimethoxyphenyl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-methyl-6-(4-morpholinophenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-3-isopropyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

4-(3-methyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)benzonitrile;

(4R)-4-((1R)-1-(6-(3,4-dimethoxyphenyl)-2,3-dimethyl-3a,7a-dihydro-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-3-(2,2,2-trifluoroethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3,4dimethoxyphenyl)-3-(oxetan-3-yl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-(2,2-difluoroethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-3-(fluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3-fluoro-4-methoxyphenyl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

2-methoxy-5-(3-methyl-4-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidzo[4,5-c]pyridin-6-yl)benzonitrile2-methoxy-5-(3-methyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)benzonitrile;

(R)-4-((R)-1-(3methyl-6-phenyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-methyl-6-(3morpholinophenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(2-tert-butylthiazol-4-yl)-3methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(3-methyl-6-(pyrazolo[1,5-a]pyridin-3-yl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4((R)-1-(3-methyl-6-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(2-tert-butylthiazol-5-yl)-3methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-cyclohexenyl-3-methyl-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

-4-(3-methyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)pyridin-2(1H)-one;

7-(3-methyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one;

(R)-4-((R)-1-(3methyl-6-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1((6-(benzo[d]thiazol-5-yl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-methyl-6-(2-methylbenzo[d]thiazol-5-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-methyl -6-methyl-1H-indazol-5-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-methyl-6-(1-methyl-1H-indazol-6-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(1,3-dimethyl-1H-indazol-5-yl)-3-H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-methyl-6-(4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(3,4-dimethoxyphenyl)3-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)propyl)pyrrolidin-2-one;

(R)-4-((S)-1-((6-(3,4-dimethoxyphenyl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)-2,2,2-trifluoroethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-methyl-6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(4-(4-acetylpiperazin-1-yl)phenyl)-3methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-7-((R)-1-((3-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)-5-azaspiro[2,4]heptan-4-one;

N,N-dimethyl-4-(3-methyl-4-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-3H-imidazo[4,5-c]pyridin-6-yl)benzenesulfonamide;

(R)-4-((R)-1-((3-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-2-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((3-cyclopropyl-6-(3,4-dimethoxyphenyl)-2-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one; and

(R)-4-((R)-1-((6-(3,4-dimethoxyphenyl)-3-isopropyl-2-methyl-3-H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(tert-butyl)-1H-pyrazol-4-yl)-1-methyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4((R)-1-((1-methyl-5-(6-(trifluoromethyl)pyridin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(6-methoxypyridin-2-yl)-1-methyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(5,6-dimethoxypyridin-2-yl)-1,2-dimethyl-1H-benzo[d]-imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(5,6-dimethoxypyridin-2-yl)-1-methyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(3,4-dimethoxyphenyl)-1-methyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(6-aminopyridin-2-yl)-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(5-(4-morpholinopiperidin-1yl)pyridin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(1-cyclopropyl-5-(5-(4-(oxetan-3-yl)piperidin-1-yl)pyridin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(4R)-4-((1R)-1-((5-(5-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)pyridin-2yl)-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-(oxetan-3-yl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(1-(tert-butyl)-1H-pyrazol-4-yl)-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1cyclopropyl-5-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(3-fluoro-4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

5-(1-cyclopropyl-7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)-1H-benzo[d]imidazol-5-yl)-2-(4-(oxetan-3-yl)piperazin-1-yl)benzonitrile;

(R)-4-((R)-1-((1-cyclopropyl-5-(5-(4-(oxetan-3-yl)piperazin-1yl)pyridin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)4-((R)-1-((1cyclopropyl-5-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(6-(4-(oxetan-3-yl)piperazin-1-yl)pyridazin-3-yl)-1-H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(3,3-dimethylindolin-6-yl)1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(pyrimidin-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-phenyl-1H-henzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(pyrazin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(pyridin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-methyl-1,2,3,4-tetrahydroquinoxalin-6-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-methyl-1-H-indazol-5-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(4-(difluoromethoxy)-3-methoxyphenyl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(thiazol-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(2-(2-hydroxypropan-2-yl)thiazol-5-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(2-methylthiazol-4yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-(tetrahydro-2H-pyran-4-yl)-1H pyrazol-5-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(4,5-dimethylthiazol-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(4-(tert-butyl)thiazol-2-yl)-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(2-(tetrahydro-2H-pyran-4-yl)thiazol-5-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1,5-dimethyl-1H-pyrazol-3-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1,2-dimethyl-1H-imidazol-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(5-methyl-1,3,4-thiadiazol-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1((5-(1-(tert-butyl)-1H-pyrazol-3yl)-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(2-methyl-1H-imidazol-5-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(5-methylthiazol-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((1-cyclopropyl-5-(1-methyl-1H-pyrazol-3-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one; and

(R)-4-((R)-1-((1-cyclopropyl-5-(2-methyl-2H-1,2,3,-triazol-4-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(1-cyclobutyl-1H-pyrazol-4-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((-5-(1-isopropyl-1H-pyrazol-4-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(1-(tert-butyl)-1H-pyrazol-4-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(1-ethyl-1H-pyrazol-3-yl)benzol[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(1-(tert-butyl)-1H-pyrazol-4-yl)-2-methylbenzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(1-isopropyl-1H-pyrazol-3-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(5-morpholinopyridin-2-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

tert-butyl 4-(6-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)pyridin-3-yl)piperazine-1-carboxylate;

(R)-4-((R)-1-((5-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(5-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)pyridin-2-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(5,6-dimethoxypyridin-2-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(4-morpholinophenyl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(3,4-dimethoxyphenyl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((5-(3,4-dimethoxyphenyl)-2-methylbenzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

tert-butyl 4-(4-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)phenyl)piperazine-1-carboxylate;

(R)-4-((R)-1-([4,5′-bibenzo[d]thiazol]-7′-yloxy)ethyl)pyrrolidin-2-one,

(S)-4-((S)-1-((5-(2-(tert-butyl)thiazol-5-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one; and

(R)-4-((R)-1-((5-(1methyl-1H-thieno[3,2-c]pyrazol-5-yl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-(6-(benzo[d]thiazol-4-yl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

(R)-4-((R)-1-((6-(benzo[d]thiazol-5-yl)-3-methyl-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one; and

(R)-4-((R)-1-((3-methyl-6-(2-methylbenzo[d]thiazol-5-yl)-3H-imidazo[4,5-c]pyridin-4-yl)oxy)ethyl)pyrrolidin-2-one;

or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof.

17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or ester thereof, and at least one pharmaceutically acceptable carrier or excipient.

18. A method for modulating spleen tyrosine kinase activity in a patient with a disorder, disease or condition, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, ester, stereoisomer, mixture of stereoisomers or tautomer thereof, wherein said disorder, disease or condition is selected from the group consisting of an inflammatory disorder, an allergic disorder, an autoimmune disease and cancer.

19. The method of claim 18 , wherein said disorder, disease or condition is acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma, myelodysplastic syndrome, myeloproliferative disease, chronic myeloid leukemia, multiple myeloma, non-Hodgkin's lymphoma, mantle cell lymphoma, follicular lymphoma, Waldestrom's macroglobulinemia, T-cell lymphoma, B-cell lymphoma, diffuse large B-cell lymphoma, pancreatic cancer, bladder cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, hepatocellular cancer, lung cancer, ovarian cancer, cervical cancer, gastric cancer, esophageal cancer, head and neck cancer, melanoma, neuroendocrine cancer, central nervous system cancer, brain cancer, bone cancer, soft tissue sarcoma, non-small cell lung cancer, small-cell lung cancer, colon cancer, systemic lupus erythematosus, myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiple sclerosis, Sjoegren's syndrome, autoimmune hemolytic anemia, asthma, rheumatoid arthritis, multiple sclerosis, or lupus, psoriasis, ulcerative colitis, Crohn's disease, irritable bowel syndrome, dennatomyositis, or multiple sclerosis.

20. The method of claim 18 , wherein said disorder, disease or condition is lymphoma, multiple myeloma or leukemia.