Quinazoline derivatives for the treatment of cancer

A compound according to the formula I,

• or pharmaceutically acceptable salts thereof, wherein
• R0 is hydrogen, halogen, cyano, nitro, or —A—R0′,
• wherein
• A is a bond, —O—, —S—, —N(R0′)—, —N(R0′)CO—, —N[C(O)R0′]C(O)—, —N(R0′)SO2—, —SO2N(R0′)—, —SO2—, —CO—, —CO2—, or —C(O)N(R0′)—;
• and
• each R0 is independently hydrogen, C1-C10 haloalkyl, C1-C10 alkyl, C3-C10cycloalkyl, C2-C10 heterocycloalkyl, aryl, heteroaryl, wherein
• each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di—(C1-C6) alkylamino, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di-(C1-C6) alkylamino, halo(C1-C6)alkyl, or carboxamide;
• Q1, Q4, and Q5 are each CR1, wherein
• each R1 is hydrogen, halogen, cyano, nitro, or —B—R1,
• wherein
• B is a bond, —O—, —S—, —N(R1′)—, —N(R1′)CO—, —N[C(O)R1′]—C(O)—, —N(R1′)SO2, —SO2N(R1′)—, —SO2—, —CO—, —CO2—, or —C(O)N(R1′)—;
• and
• each R1 is independently hydrogen, C1-C10 haloalkyl, C1-C10 alkyl, C3-C10 cycloalkyl, C2-C10 heterocycloalkyl, aryl, heteroaryl, wherein
• each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1—C6 alkoxy, halogen, hydroxy, carboxy, oxo, amino, mono- or di-(C1-C6) alkylamino, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di—(C1-C6) alkylamino, halo(C1-C6)alkyl, or carboxamide;
• Q2 is N, Q3 is CR2, wherein
• each R2 is independently
• (a)H,
• (b) halogen, or
• (c) a C1-C15 alkyl group where up to five of the carbon atoms in said alkyl group are optionally replaced independently by R22, carbonyl, ethenyl, ethynyl or a moiety selected from N, O, S SO2 or SO, with the proviso that two O atoms, two S atoms, or an O and S atom are not immediately adjacent each other, wherein
• R22 is
• (i) heteroaryl,
• (ii) aryl,
• (iii) saturated or unsaturated C3-C10 cycloalkyl, or
• (iv) saturated or unsaturated C2-C10 heterocycloalkyl, wherein each aryl, heteroaryl, saturated or unsaturated cycloalkyl, or saturated or unsaturated heterocycloalkyl, independently, is optionally substituted with at least one group, which independently is hydroxy, halo, amino, cyano, carboxy, carboxamido, nitro, oxo, —S—(C1-C6)alkyl, —SO2—(C1- C6)alkyl, —SO2—aryl, —SO—(C1-C6)alkyl, —SO—aryl, —SO2NH2, —SO2NH—(C1-C6)alkyl, —SO2NH—aryl, (C1-C6)alkoxy, or mono- or di—(C1-C10)alkylamino;
• and
• each R22 is optionally fused to a C6-C10 aryl group, C5—C8 saturated cyclic group,
• or a C5—C10 heterocycloalkyl group;
• wherein each (c) is optionally substituted at any available position with C1-C10 alkyl, C1-C10 haloalkyl, C2-C10 alkenyl, C2-C10 alkynyl, hydroxy, carboxy, carboxamido, oxo, halo, amino, cyano, nitro, —SH, —S—(C1-C6)alkyl, —SO2—(C1-C6)alkyl, —SO2NH2, —SO2NH—(C1-C6)alkyl, —SO2NH—aryl, —SO2—aryl, —SO—(C1-C6)alkyl, —SO2—aryl, C1- C6 alkoxy, C2-C10 alkenyloxy, C2-C10 alkynyloxy, mono-or di—(C1-C10)alkylamino, or R23, wherein
• R23 is
• (1) heteroaryl,
• (2) aryl,
• (3) saturated or unsaturated C5-C10 cycloalkyl, or
• (4) saturated or unsaturated C5-C10heterocycloalkyl, and
• the R23 groups are optionally substituted at least one group which is independently hydroxy, oxo, halo, amino, cyano, nitro, —SH, —S—(C1- C6)alkyl, —SO2—(C1-C6)alkyl, —SO2—aryl, —SO—(C1-C6)alkyl, —SO—aryl, —SO2NH2, —SO2NH—(C1-C6)alkyl, —SO2NH—aryl, (C1-C6)alkoxy, or mono- or di—(C1-C10)alkylamino;
• R7 is O—;
• X1 is N or CRc, Y is CRc, wherein
• each Rc independently is hydrogen, halogen, cyano, nitro, C1-C10 alkyl,C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 haloalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C10)alkyl, heterocycloalkyl, aryl, or heteroaryl, wherein
• each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group is optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di—(C1-C6) alkylamino, cyano, nitro, halo (C1-C6)alkyl, halo(C1-C6)alkoxy, carboxamide, heterocycloalkyl, aryl, or heteroaryl, wherein
• the aryl and heteroaryl groups are optionally substituted with from 1-4 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, amino, mono- or di—(C1-C6) alkylamino, halo(C1-C6)alkyl, or carboxamide
• X2 and X3 are independently C(R5)(R6), wherein
• each R5 and R6 is independently hydrogen, C1-C6 alkyl, or mono- or di—(C1-C6)alkylamino(C1-C6)alkykl;
• n is 1.