Fused pyrrole derivatives as PI3K inhibitors

1. A compound of Formula IIa or IIIa:

or a pharmaceutically acceptable salt thereof; wherein:

Cy is heterocycloalkyl, aryl or heteroaryl, each of which is optionally substituted with 1, 2, 3, 4, or 5 independently selected R C groups;

each R C is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from hydroxy, C 1-6 alkoxy, and C 1-6 haloalkoxy;

Ar is a moiety of formula:

R 1 is C 1-6 alkyl;

R 2 , R 3 , R 4 , and R 5 are each independently selected from H, halo, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy;

R 6 is H, CN, halo, or C 1-6 alkyl;

each R a , R c , and R d is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 1-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino; and

each R b is independently selected from C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino;

or any R c and R d together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy is aryl, optionally substituted with 1, 2, 3, 4, or 5 independently selected R C groups.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy is a phenyl ring, which is optionally substituted with 1, 2, 3, 4, or 5 independently selected R C groups.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R C is independently halo.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl.

6. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Cy is aryl, optionally substituted with 1, 2, 3, 4, or 5 independently selected R C groups;

each R C is independently selected from halo;

Ar is a moiety of formula:

R 1 is C 1-6 alkyl;

R 2 , R 3 , R 4 , and R 5 are each independently selected from H, halo, CN, C 1-6 alkyl, and C 1-6 haloalkyl;

and R 6 is selected from H, halo, CN, and C 1-6 alkyl.

7. The compound of claim 1 , having Formula IIa:

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , having Formula IIIa:

or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 , selected from:

N-{1-[6-chloro-1-(3-fluorophenyl)-1H-indol-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[4-chloro-1-(3-fluorophenyl)-1H-indol-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-chloro-1-(3-fluorophenyl)-1H-indol-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3,4-dichloro-1-(3-fluorophenyl)-1H-indol-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-bromo-1-(3-fluorophenyl)-1H-indol-2-yl]ethyl}-9H-purin-6-amine;

N-{1-[3-chloro-1-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]ethyl}-9H-purin-6-amine;

N-(1-(1-(3-fluorophenyl)-1H-pyrrolo[2,3-b)]pyridin-2-yl)ethyl)-9H-purin-6-amine;

N-{1-[1-(3-fluorophenyl)-3-methyl- 1H-indol-2-yl]ethyl}-9H-purin-6-amine;

2-(1-(9H-purin-6-ylamino)ethyl)-1-(3-fluorophenyl)-1H-indole-3-carbonitrile; and

N-(1-(3-fluoro-1-(3-fluorophenyl)-1H-pyrrolo[2,3-b)]pyridin-2-yl)ethyl)-9H-purin-6-amine;

or a pharmaceutically acceptable salt of any of the aforementioned.

10. A composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

11. A method of inhibiting an activity of a PI3δ kinase, comprising contacting the kinase with a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

12. The compound of claim 6 , having Formula IIa:

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 6 , having Formula IIIa:

or a pharmaceutically acceptable salt thereof.

14. A method of treating rheumatoid arthritis in a patient, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said treating refers to inhibiting or ameliorating.

15. A method of treating acute myeloblastic leukemia in a patient, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said treating refers to inhibiting or ameliorating.

16. A method of treating B cell lymphoma in a patient, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said treating refers to inhibiting or ameliorating.

17. A method of treating chronic myeloid leukemia in a patient, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said treating refers to inhibiting or ameliorating.

18. A method of treating diffuse large B cell lymphoma in a patient, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said treating refers to inhibiting or ameliorating.