Inhibitors of PI3 kinase

1. A compound of Formula I

or a pharmaceutically acceptable salt thereof,

wherein Q is a ring

wherein the ring has 0, 1, 2, or 3 substituents on carbon atoms that are independently selected from R;

X 1 is N or CR;

R 1 is halo, —CF 3 , —C 1 - 6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —OC 1 - 6 alkyl, or —CN, wherein the —C 1-6 alkyl, —C 2-6 alkenyl, or —C 2-6 alkynyl are substituted by 0, 1, 2 or 3 substituents independently selected from —C 1-8 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, C 1-4 haloalkyl, halo, —CN, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O)2R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a , —NR a C 2-6 alkylOR a , or a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic ring or 6-, 7-, 8-, 9-, or 10-membered bicylcic ring containing 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, wherein the ring is further substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, C 1-4 haloalkyl, halo, —CN, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a or —NR a C 2-6 alkylOR a ;

X 2 is —N(R a )S(═O) 2 (CR a R a ) n —, —N(R a )C(═O)(CR a R a ) n —, —O(CR a R a ) n —, —(CR a R a ) n O—, —(CR a R a ) n S(═O) m —, —(CR a R a ) n N(R a )—, —N(R a )(CR a R a ) n —, —S(O) m (CR a R a ) n —, —S(═O) 2 N(R a )(CR a R a ) n —, —N(R a )C(═O)O(CR a R a ) n —, —N(R a )C(═O)NR a (CR a R a ) n —, —N(R a )C(═NR a )NR a (CR a R a ) n —, —OC(═O)NR a (CR a R a ) n —, or —N(R a )S(═O) 2 NR a (CR a R a ) n —;

Z is hydrogen, —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C(═O)R a , or a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic ring or 6-, 7-, 8-, 9-, or 10-membered bicylcic ring containing 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, wherein the —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, or ring are substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, C 1-4 haloalkyl, halo, —CN, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a or —NR a C 2-6 alkylOR a ;

each R is independently hydrogen, C 1-4 haloalkyl, halo, —CN, nitro, —C(═O)NR a R a , —C(═O)R b , —C(═O)OR b , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —O—C 1-6 alkylN(R a )C(═O)OR b , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a , —NR a C 2-6 alkylOR a , —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, or a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic ring or 6-, 7-, 8-, 9-, or 10-membered bicylcic ring containing 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, wherein the —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, or ring are substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a , —NR a C 2-6 alkylOR a , —N(R a )(CR a R a ) n —Y, —(CR a R a ) n Y, or —(CR a R a ) n OR a ;

each R f is independently, C 1-4 haloalkyl, halo, —CN, nitro, —C(═O)NR a R a , —C(═O)R b , —C(═O)OR b , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —O—C 1-6 alkylN(R a )C(═O)OR b , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a , —NR a C 2-6 alkylOR a , —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, wherein the —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl are substituted by 0, 1, 2 or 3 substituents independently selected from C 1-8 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, C 1-4 haloalkyl, halo, cyano, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a , —NR a C 2-6 alkylOR a , —N(R a )(CR a R a ) n —Y, —(CR 1 R a ) n Y, or —(CR a R a ) n OR a ;

Y is a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic ring or 6-, 7-, 8-, 9-, or 10-membered bicylcic ring containing 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O and S, which is substituted with 0, 1, or 2 substitutents independently selected from C 1-8 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, C 1-4 haloalkyl, halo, —CN, nitro, —C(═O)R b , —C(═O)OR b , —C(═O)NR a R a , —C(═NR a )NR a R a , —OR a , —OC(═O)R b , —OC(═O)NR a R a , —OC(═O)N(R a )S(═O) 2 R b , —OC 2-6 alkylNR a R a , —OC 2-6 alkylOR a , —SR a , —S(═O)R b , —S(═O) 2 R b , —S(═O) 2 NR a R a , —S(═O) 2 N(R a )C(═O)R b , —S(═O) 2 N(R a )C(═O)OR b , —S(═O) 2 N(R a )C(═O)NR a R a , —NR a R a , —N(R a )C(═O)R b , —N(R a )C(═O)OR b , —N(R a )C(═O)NR a R a , —N(R a )C(═NR a )NR a R a , —N(R a )S(═O) 2 R b , —N(R a )S(═O) 2 NR a R a , —NR a C 2-6 alkylNR a R a or —NR a C 2-6 alkylOR a ;

each R a is independently hydrogen or R b ;

each R b is independently phenyl, benzyl or C 1-6 alkyl, wherein the phenyl, benzyl or C 1-6 alkyl is substituted by 0, 1, 2 or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-3 haloalkyl, —OC 1-4 alkyl, —NH 2 , —CN, —NHC 1-4 alkyl, or —N(C 1-4 alkyl) 2 ;

each n is independently 0, 1, 2, or 3; and

each m is independently 0, 1, or 2.

2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is halo or —CF 3 .

3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is chlorine.

4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 1 is CH.

5. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X 2 is —NHSO 2 — or —N(CH 3 )SO 2 —.

6. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is phenyl or phenyl substituted with halo or —OCH 3 .

7. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is Cl; X 1 is CH; X 2 is —NHSO 2 — and Z is fluorophenyl.

8. A pharmaceutical composition comprising:

A) a compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof, and

B) a pharmaceutically acceptable excipient.

9. A compound, or a pharmaceutically acceptable salt thereof, selected from:

N-(2-chloro-5-(4-chloro-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide;

tert-butyl (2-((6-(6-chloro-5-(((4- fluorophenyl)sulfonyl)amino)-3-pyridinyl)-4-quinolinyl)oxy)ethyl)carbamate;

N-(2-chloro-5-(4-phenoxy-6-quinolinyl)-3-pyridinyl)methanesulfonamide;

N-(2-chloro-5-(4-methoxy-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide;

N-(2-chloro-5-(4-chloro-6-quinolinyl)-3-pyridinyl)methanesulfonamide;

N-(2chloro-5-(4-hydroxy-6-quinolinyl)-3-pyridinyl)-4-fluorbenzenesulfonamide;

N-(2-chloro-5-(4-(2-methoxyethoxy)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide;

N-(2-chloro-5-(4-(dimethylamino)-6-quinolinyl)-3-pyridinyl)-4-methoxybenzenesulfonamide;

2-chloro-5-(4-chloro-6-quinolinyl)-N,N-dimethyl-3-pyridinamine;

N-(2-chloro-5-(4-(((5-cyclopropyl-1,2,4-oxadiazol-3-yl)methyl)(ethyl)amino)-6-quinolinyl)-3-pyridinyl)methanesulfonamide;

N-(2-chloro-5-(4-((2-cyanoethyl)(ethyl)amino)-6-quinolinyl)-3-pyridinyl)methanesulfonamide;

N-(2-chloro-5-(4-((2-methoxy-2-methylpropyl)amino)-6-quinolinyl)-3-pyridinyl)methanesulfonamide;

N-(2-chloro-5-(4-((3-fluorobenzyl)(methyl)amino)-6-quinolinyl)-3-pyridinyl)methanesulfonamide;

N-(2-chloro-5-(4-((2,5-dimethoxybenzyl)amino)-6-quinolinyl)-3-pyridinyl)methanesulfonamide;

N-(2-chloro-5-(4-(4-piperidinylamino)-6-quinolinyl)-3-pyridinyl)methanesulfonamide;

N-(2-chloro-5-(4-(dimethylamino)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide;

N-(2-chloro-5-(4-((2-methoxyethyl)amino)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide;

N-(2-chloro-5-(4-((2-methoxy-1-methylethyl)amino)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide;

N-(2-chloro-5-(4-(tetrahydro-2H-thiopyran-4-ylmethoxy)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide;

N-(2-chloro-5-(4-(tetrahydro-3-thiophenyloxy)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamide;

N-(2-chloro-5-(4-((tetrahydro-2H-thiopyran-1,1-dioxide-4-yl)methoxy)quinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide;

N-(2-chloro-5-(4-(tetrahydrothiophen-1,1-dioxide-3-yloxy)quinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide;

N′-(2-chloro-5-(4-chloro-6-quinolinyl)-3-pyridinyl)-N,N-dimethylsulfamide; or

N′-(2-chloro-5-(4((2-methoxyethyl)(methyl)amino)-6-quinolinyl)-3-pyridinyl)-N-(2-methoxyethyl)-N-methylsulfamide.