Substituted fused aryl and heteroaryl derivatives as PI3K inhibitors

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof; wherein:

the symbol

 indicates that the ring is aromatic;

Z is O, S, or NR A ;

Cy is cycloalkyl, heterocycloalkyl, aryl or heteroaryl, each 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, halosulfanyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR 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 , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 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, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, Cy 1 , NO 2 , OR a , SR 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 , C(═NR e )NR c R d , NR c C(═NR e )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 , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 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 ;

W is CR 3 ; V is CR 4 or N; X is CR 5 ; Y is CR 6 or N; and U is CR 7 or N; or

W is CR 3 ; V is CR 4 or N; X is O or S; Y is absent; and U is CR 7 or N; or

W is CR 3 ; V is N; X is CR 5 ; Y is absent; and U is NR A1 ; or

W is CR 3 ; V is O or S; X is CR 5 ; Y is absent; and U is CR 7 or N;

provided that when Y is present, then at least one of V, Y, and U is other than N;

R 1 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl; wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from halo, OH, CN, NR 1† R 2† , C 1-6 alkoxy, C 1-6 haloalkoxy, 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, and C 1-6 alkylcarbonylamino;

each R 1† and R 2† is independently selected from H and C 1-6 alkyl;

or any R 1† and R 2† together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from C 1-6 alkyl;

R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are each independently selected from H, OH, NO 2 , CN, halo, C 1-6 alkyl, 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, and C 1-6 alkoxycarbonyl;

Ar is

R D is selected from H, —(C 1-4 alkyl) r -Cy 1 , halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , C(═NR e )NR c1 R d1 , NR c1 C(═NR e )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;

R A is selected from H, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl;

R A1 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl;

each Cy 1 is, independently, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , C(═NR e )NR c1 R d1 , NR c1 C(═NR e )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;

each R a , R b , 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 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR f )NR c5 R d5 , NR c5 C(═NR f )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;

or any R c and R d together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR f )NR c5 R d5 , NR c5 C(═NR f )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;

each R e and R f is independently selected from H, C 1-6 alkyl, CN, OR a5 , SR b5 , S(O) 2 R b5 , C(O)R b5 , S(O) 2 NR c5 R d5 , and C(O)NR c5 R d5 ;

each R a1 , R b1 , R c1 , and R d1 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 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR f )NR c5 R d5 , NR c5 C(═NR f )NR c5 R d5 , S(O)R b5 , S(O)NR c5 , R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;

or any R c1 and R d1 together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or a heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR f )NR c5 R d5 , NR c5 C(═NR f )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;

each R a5 , R b5 , R c5 , and R d5 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, di(C 1-6 alkyl)amino, C 1-6 haloalkyl, and C 1-6 haloalkoxy;

or any R c5 and R d5 together with the N atom to which they are attached form a 3-, 4-, 5-, 6-, or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, di(C 1-6 alkyl)amino, C 1-6 haloalkyl, and C 1-6 haloalkoxy; and

r is 0 or 1;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

W is CR 3 ;

V is CR 4 or N;

X is CR 5 ; and Y is CR 6 or N; or

X is O or S; and Y is absent;

U is CR 7 or N; and

each R c is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR 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 , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 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, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a , SR 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 , C(═NR e )NR c R d , NR c C(═NR e )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 , NR b S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 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 .

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein Z is NR A .

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

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

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R C is independently selected from C 1-6 alkyl, halo, OR a , and NR c C(O)R b , wherein said C 1-6 alkyl is optionally substituted with hydroxyl or C 1-4 alkoxy.

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

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R C is independently selected from halo, C 1-6 alkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c C(O)R b , NR c C(O)OR a , or NR c S(O) 2 R b ; wherein said C 1-6 alkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, CN, OR a , and NR c C(O)R b .

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R D is H.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from H and C 1-6 alkyl.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are independently selected from H, CN, halo, C 1-6 alkyl, and C 1-6 haloalkyl.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is H, CN, halo, C 1-3 alkyl, or C 1-3 haloalkyl; and R 3 , R 4 , R 5 , R 6 , and R 7 are each independently H or C 1-3 alkyl.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R A is H.

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

Z is NR A ;

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

each R C is independently selected from C 1-6 alkyl, halo, OR a , and NR c C(O)R b , wherein said C 1-6 alkyl is optionally substituted with hydroxyl or C 1-4 alkoxy;

each R a , R b , and R c is independently selected from H and C 1-4 alkyl;

Ar is a moiety of formula:

R D is selected from H, methyl and amino,

R 1 is methyl;

R A is H;

R 2 is H or halo; and

R 3 , R 4 , R 5 , R 6 , and R 7 are each independently H or methyl.

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

Z is NR A ;

Cy is heterocycloalkyl, aryl or heteroaryl, each 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, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c C(O)R b , NR c C(O)OR a , or NR c S(O) 2 R b ; wherein said C 1-6 alkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halosulfanyl, CN, NO 2 , OR a , SR 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 , C(═NR e )NR c R d , NR c C(═NR e )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 , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 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 ;

Ar is a moiety of formula:

R 1 is independently selected from H and C 1-6 alkyl;

R A is selected from H and C 1-6 alkyl; and

R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are each independently selected from H, halo, CN, C 1-6 alkyl, and C 1-6 haloalkyl.

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

Z is NR A ;

Cy is heterocycloalkyl, aryl or heteroaryl, each 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, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, OR a , C(O)R b , C(O)NR c R d , C(O)OR a , NR c C(O)R b , NR c C(O)OR a , or NR c S(O) 2 R b ; wherein said C 1-6 alkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C 1-6 alkyl, CN, OR a , and NR c C(O)R b ;

Ar is a moiety of formula:

R 1 is independently selected from H and C 1-6 alkyl;

R A is selected from H and C 1-6 alkyl; and

R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are each independently selected from H, halo, CN, C 1-6 alkyl, and C 1-6 haloalkyl.

17. The compound of claim 1 having Formula Ia, Ib, Ic, or Id:

or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 1 , having Formula IIa, IIb, IIc, or IId:

or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 2 , selected from:

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

N-{1-[4-(3-fluorophenyl)-2-methyl-1,3-benzothiazol-5-yl]ethyl}-9H-purin-6-amine;

N(6)-{1-[1-(5-fluoropyridin-3-yl)-2-naphthyl]ethyl}-9H-purine-2,6-diamine;

N(6)-{1-[1-(3-fluorophenyl)-2-naphthyl]ethyl}-9H-purine-2,6-diamine;

N-{1-[1-(5-fluoropyridin-3-yl)-2-naphthyl]ethyl}-9H-purin-6-amine;

N-{1-[8-(3,5-difluorophenyl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-(2-fluorophenyl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-(3-fluorophenyl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-(5-fluoropyridin-3-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-chloro-8-(2-fluorophenyl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-(1-{5-chloro-8-[4-(2-methoxyethyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

(3R)-1-{5-chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}pyrrolidin-3-ol;

N-((3S)-1-{5-chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}pyrrolidin-3-yl)acetamide;

N-(1-{5-chloro-8-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-{1-[5-chloro-8-(3-fluorophenyl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

or a pharmaceutically acceptable salt thereof.

20. The compound according to claim 2 , selected from:

N-{1-[5-Chloro-8-(3-fluorophenyl)cinnolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Fluoro-8-(3-fluorophenyl)cinnolin-7-yl]ethyl}-9H-purin-6-amine;

N(6)-{1-[5-Fluoro-8-(3-fluorophenyl)cinnolin-7-yl]ethyl}-9H-purine-2,6-diamine;

N-{1-[5-Chloro-8-(3,5-difluorophenyl)cinnolin-7-yl]ethyl}-9H-purin-6-amine; and

N-{1-[5-Chloro-8-(2-fluorophenyl)cinnolin-7-yl]ethyl}-9H-purin-6-amine;

or a pharmaceutically acceptable salt thereof.

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

N-{1-[8-(3,5-difluorophenyl)-5-fluorocinnolin-7-yl]ethyl}-9H-purin-6-amine;

N-{[5-Chloro-8-(3-fluorophenyl)cinnolin-7-yl]methyl}-9H-purin-6-amine;

N-{1-[5-chloro-8-(3-fluorophenyl)cinnolin-7-yl]propyl}-9H-purin-6-amine;

N-{1-[5-chloro-8-(5-fluoropyridin-3-yl)cinnolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-(3-fluorophenyl)-5-methylcinnolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-(3,5-difluorophenyl)-5-methylcinnolin-7-yl]ethyl}-9H-purin-6-amine;

3-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]cinnolin-8-yl}-5-fluoro-N-methylbenzamide;

N-{1-[5-Chloro-8-(3-fluoro-4-methoxyphenyl)cinnolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(2-fluoropyridin-4-yl)cinnolin-7-yl]ethyl}-9H-purin-6-amine;

1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidin-4-ol;

1-{4-Chloro-2-[1-(9H-purin-6-ylamino)ethyl]-1-naphthyl}piperidin-4-ol;

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

N-{1-[5-Chloro-8-(4,4-difluoropiperidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

(3S)-1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidin-3-ol;

1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}-4-phenylpiperidin-4-ol;

N-{1-[8-(3-Fluorophenyl)-5-methylquinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Ethyl-8-(3-fluorophenyl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

8-(3-fluorophenyl)-7-[1-(9H-purin-6-ylamino)ethyl]quinoline-5-carbonitrile;

(3R)-1-{5-fluoro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}pyrrolidin-3-ol;

N-{1-[8-(4-Cyclobutylpiperazin-1-yl)-5-fluoroquinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(3-fluorophenyl)isoquinolin-7-yl]ethyl}-9H-purin-6-amine;

N-(1-{5-Chloro-8-[(3S)-3-fluoropyrrolidin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

2-(4-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperazin-1-yl)ethanol;

1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidine-4-carbonitrile;

1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}pyrrolidine-3-carbonitrile;

N-{1-[5-Chloro-8-(3-fluoropiperidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(4-fluoropiperidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

(1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidin-3-yl)methanol;

(1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidin-4-yl)methanol;

N-{1-[5-Chloro-8-(4-cyclohexylpiperazin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(4-cyclopropylpiperazin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(3-methoxypiperidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(3-methoxypyrrolidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(4-cyclobutylpiperazin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[8-(1,4′-Bipiperidin-1′-yl)-5-chloroquinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(4-methoxypiperidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(4-phenylpiperidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

2-(1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidin-4-yl)ethanol;

N-(1-{5-Chloro-8-[4-(pyridin-4-ylmethyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-{1-[5-Chloro-8-(4-phenoxypiperidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-{1-[5-Chloro-8-(3-phenylpyrrolidin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-((3S)-1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}pyrrolidin-3-yl)propanamide;

N-((3S)-1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}pyrrolidin-3-yl)-2-methylpropanamide;

Methyl ((3S)-1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}pyrrolidin-3-yl)carbamate;

N-((3S)-1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}pyrrolidin-3-yl)methanesulfonamide;

N-(1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidin-4-yl)methanesulfonamide;

N-(1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidin-4-yl)acetamide;

Methyl (1-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperidin-4-yl)carbamate;

N-(1-{5-Chloro-8-[4-(cyclopropylcarbonyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

Methyl 4-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperazine-1-carboxylate;

N-(1-{5-Chloro-8-[4-(cyclobutylcarbonyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-(1-{5-Chloro-8-[4-(methoxyacetyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

4-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}-N,N-dimethylpiperazine-1-carboxamide;

N-{1-[8-(4-Benzoylpiperazin-1-yl)-5-chloroquinolin-7-yl]ethyl}-9H-purin-6-amine;

2-(4-{5-Chloro-7-[1-(9H-purin-6-ylamino)ethyl]quinolin-8-yl}piperazin-1-yl)-N,N-dimethylacetamide;

N-(1-{5-Chloro-8-[4-(4-fluorobenzoyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-(1-{5-Chloro-8-[4-(3-fluorobenzoyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-(1-{5-Chloro-8-[4-(2-fluorobenzoyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-[1-(8-{4-[(1-Acetylpiperidin-4-yl)carbonyl]piperazin-1-yl}-5-chloroquinolin-7-yl)ethyl]-9H-purin-6-amine;

N-(1-{5-Chloro-8-[4-(pyridin-2-ylcarbonyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-(1-{5-Chloro-8-[4-(pyridin-3-ylcarbonyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-(1-{5-Chloro-8-[4-(pyrazin-2-ylcarbonyl)piperazin-1-yl]quinolin-7-yl}ethyl)-9H-purin-6-amine;

N-{1-[5-Chloro-8-(4-isonicotinoylpiperazin-1-yl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-[1-(5-Chloro-8-{4-[(5-methylisoxazol-3-yl)carbonyl]piperazin-1-yl}quinolin-7-yl)ethyl]-9H-purin-6-amine;

N-[1-(5-Chloro-8-{4-[(3,5-dimethylisoxazol-4-yl)carbonyl]piperazin-1-yl}quinolin-7-yl)ethyl]-9H-purin-6-amine;

N-[1-(5-Chloro-8-{4-[(1-methyl-1H-pyrazol-3-yl)carbonyl]piperazin-1-yl}quinolin-7-yl)ethyl]-9H-purin-6-amine;

N-{1-[5-fluoro-8-(3-fluorophenyl)quinolin-7-yl]ethyl}-9H-purin-6-amine;

N-[1-(5-Fluoro-8-{4-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperazin-1-yl}quinolin-7-yl)ethyl]-9H-purin-6-amine;

N-{1-[4-Chloro-7-(3-fluorophenyl)-2,1-benzisoxazol-6-yl]ethyl}-9H-purin-6-amine;

N-{1-[4-Chloro-7-(3-fluorophenyl)-1H-indazol-6-yl]ethyl}-9H-purin-6-amine;

N-{1-[4-Chloro-7-(3,5-difluorophenyl)-1H-indazol-6-yl]ethyl}-9H-purin-6-amine;

N-{1-[4-Chloro-7-(3,5-difluorophenyl)-1-methyl-1H-indazol-6-yl]ethyl}-9H-purin-6-amine;

or a pharmaceutically acceptable salt of any of the aforementioned.

22. A compound of claim 1 , which is N-{1-[5-chloro-8-(3-fluorophenyl)cinnolin-7-yl]ethyl}-9H-purin-6-amine, or a pharmaceutically acceptable salt thereof.

23. A compound of claim 1 , which is N-{(1S)-1-[5-chloro-8-(3-fluorophenyl)cinnolin-7-yl]ethyl}-9H-purin-6-amine, or a pharmaceutically acceptable salt thereof.

24. A compound of claim 1 , which is N-{(1S)-1-[5-chloro-8-(3-fluorophenyl)cinnolin-7-yl]ethyl}-9H-purin-6-amine adipic acid salt.

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

26. A method of inhibiting an activity of a PI3K kinase, comprising contacting the kinase with a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said PI3K kinase is PI3Kδ.

27. 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.

28. 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.