3-substituted quinoline or quinoxaline derivatives and their use as phosphatidylinositol 3-kinase (PI3K) inhibitors

摘要

Compound having the structure: ** Formula ** or any pharmaceutically acceptable salt thereof, in which: X1 is C (R9) or N; X2 is C (R10) or N; Y is N (R11), O or S; n is 0, 1, 2 or 3; R1 is a monocyclic ring of 5, 6 or 7 members saturated, partially saturated or unsaturated, attached through oxygen or by direct bond, containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, but not it contains more than one O or S, in which the available carbon atoms of the ring are substituted with 0, 1 or 2 oxo or thioxo groups, in which the ring is substituted with 0 or 1 R2 substituents, and the ring is further substituted with 0, 1, 2 or 3 substituents independently selected from halo, nitro, cyano, C1-4 alkyl, O-C1-4 alkyl, O-haloalkyl C1-4, NH-alkyl C1-4, N (C1-4 alkyl) -C1-4 alkyl and C1-4 haloalkyl; R2 is selected from halo, C1-4 haloalkyl, cyano, nitro, -C ( = O) Ra, -C ( = O) ORa, -C ( = O) NRaRa, C ( = NRa) NRaRa, -ORa, -OC ( = O) Ra, -OC ( = O) NRaRa, -OC ( = O) N (Ra) S ( = O) 2Ra, -O-C2-6-NRaRa alkyl, O-C2-6-ORa alkyl, -SRa, -S ( = O) Ra, -S ( = O) 2Ra, -S ( = O) 2NRaRa, -S ( = O) 2N (Ra) C ( = O) Ra, -S ( = O) 2N (Ra) C ( = O) ORa, S ( = O) 2N (Ra) C ( = O) NRaRa, -NRaRa, -N ( Ra) C ( = O) Ra, -N (Ra) C ( = O) ORa, -N (Ra) C ( = O) NRaRa, N (Ra) C ( = NRa) NRaRa, -N (Ra) S ( = O) 2Ra, -N (Ra) S ( = O) 2NRaRa, -NRa-C2-6-NRaRa alkyl and -NRa-C2-6-ORa alkyl; or R2 is selected from alkyl C1-6, phenyl, benzyl, heteroaryl, heterocycle, - (C1-3 alkyl) heteroaryl, - (C13 alkyl) heterocycle, -O (C1-3 alkyl) heteroaryl, -O (C1-3 alkyl) heterocycle, -NRa ( C1-3 alkyl) heteroaryl, -NRa (C1-3 alkyl) heterocycle, - (C1-3 alkyl) phenyl, -O (C1-3 alkyl) phenyl and -NRa (C1-3 alkyl) phenyl all of which are substituted with 0 , 1, 2 or 3 substituents selected from C1-4 haloalkyl, O-C1-4 alkyl, Br, Cl, F, I and C1-4 alkyl; R3 is selected from H, halo, C1-4 haloalkyl, cyano, nitro, -C ( = O) Ra, -C ( = O) ORa, -C ( = O) NRaRa, C ( = NRa) NRaRa, -ORa, -OC ( = O) Ra, -OC ( = O) NRaRa, -OC ( = O) N (Ra) S ( = O) 2Ra, -O-C2-6 alkyl NRaRa, O-C2-6-ORa alkyl, -SRa, -S ( = O) Ra, -S ( = O) 2Ra, -S ( = O) 2NRaRa, -S ( = O) 2N (Ra ) C ( = O) Ra, -S ( = O) 2N (Ra) C ( = O) ORa, S ( = O) 2N (Ra) C ( = O) NRaRa, -NRaRa, - N (Ra) C ( = O) Ra, -N (Ra) C ( = O) ORa, -N (Ra) C ( = O) NRaRa, N (Ra) C ( = NRa) NRaRa, -N (Ra) S ( = O) 2Ra, -N (Ra) S ( = O) 2NRaRa, -NRa-C2-6-NRaRa alkyl, -NRa-C2-6-ORa alkyl, C1-6 alkyl , phenyl, benzyl, heteroaryl and heterocycle, wherein C1-6 alkyl, phenyl, benzyl, heteroaryl and heterocycle are additionally substituted with 0, 1, 2 or 3 substituents selected from C1-6 haloalkyl, O- C1-6 alkyl, Br, Cl, F, I and C1-6 alkyl.