Benzoxazepines as Inhibitors of PI3K/M TOR and Methods of Their Use and Manufacture

A compound of formula I

• or a single isomer or a mixture of isomers thereof, optionally as a pharmaceutically acceptable salt thereof, wherein
• R1 is H, halo, —OH, (C1-C6)alkoxy, NH2, NH(C1-C6)alkyl, or N((C1-C6)alkyl)2;
• R2 is —NR2aS(O)2—R2b, —S(O)2—NR2aR2c, and R2a and R2c are each independantly H or (C1-C6)alkyl and R2b is (C1-C6)alkyl or halo(C1-C6)alkyl;
• R3 is H, halo, or (C1-C6)alkyl;
• R4 is H or halo;
• Q is N, C—H, or C—(C1-C6)alkyl, C—CN, or C—CF3;
• R6 is H, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkylene-NH2, (C1-C6)alkylene-NH(C1-C6)alkyl, (C1-C6)alkylene-NH(C1-C6)haloalkyl, (C1-C6)alkylene-N(C1-C6)alkyl)2, NH2, NH(C1-C6)alkyl, hydroxyalkyl, (C1-C6)alkylene-O(C1-C6)alkyl, NH(C1-C6)alkyleneNH2, NH(C1-C6)alkylene-cyloalkyl, —NH(C1-C6)alkylene-heterocyloalkyl, N((C1-C6)alkyl)2, (C1-C6)alkylene-NHSO2—(C1-C6)alkyl, (C1-C6)alkylene-NH(C═O)—(C1-C6)alkyl, —(C═O)—NH2, —(C═O)—(C1-C6)alkyl, —(C═O)—NH(C1-C6)alkyl, —(C═)—N(C1-C6)alkyl))2, —NHSO2—(C1-C6)alkyl, —S(O)—(C1-C6)alkyl, —SO2—(C1-C6)alkyl, —SO2NH2, —SO2NH(C1-C6)alkyl, —SO2N((C1-C6)alkyl)2, —CN, (C4-C7)heterocycloalkyl, (C1-C6)alkylene-(C3-C7)heterocycloalkyl, nitro, (C1-C6)alkylene-CN, NH(C1-C6)alkylene-NH(C1-C6)alkyl, NH(C1-C6)alkylene-N((C1-C6)alkyl)2, or (C1-C6)alkylene-OC(O)—(C1-C6)alkyl, where any alkylene in R6 is optionally substituted with 1, 2, or 3 groups which are independently halo or hydroxy, and wherein when any alkylene is —CH2—, then one of the hydrogens of the —CH2— can optionally be replaced by (C1-C3)haloalkyl;
• R7 is H, halo, —NH2, nitro (C1-C6)alkyl, (C1-C6)alkoxy, R7 is —CF3, halo(C1-C6)alkyl, (C1-C6)alkenyl, NH(C1-C6)alkyl, or N((C1-C6)alkyl)2;
• Y is N or C—R8, wherein R8 is H, halo, (C1-C6)alkyl, NH2, NH(C1-C6)alkyl, N((C1-C6)alkyl)2, (C2-C6)alkenyl, (C1-C6)alkylene-O(C1-C6)alkyl, hydroxyalkyl, (C1-C6)alkylene-CO2(C1-C6)alkyl, (C1-C6)alkylene-CO2H, phenyl, halo(C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)alkylene-(C3-C7)cycloalkyl, COH, CO2H, —CO2(C1-C6)alkyl, CN, (C1-C6)alkylene-CN, (C1-C6)alkylene-C≡C—H, (C1-C6)alkylene-C≡C—(C1-C6)alkyl, —C≡C—H, —C≡C—(C1-C6)alkyl, (C1-C6)alkylene-phenyl;
• where any phenyl in R8 is optionally substituted with 1, 2, or 3 groups which are independently halo or alkyl;
• or
• R7 and R8, together with the atoms to which they are attached, can be joined together to form a 5, 6, or 7 membered saturated, partially unsaturated, or unsaturated ring, optionally containing up to two heteroatoms selected from N—H, N—(C1-C6)alkyl, O, SO, and SO2 and where the ring formed by R7 and R8 is optionally substituted with one or two groups which are independently alkyl, alkoxy, or halo;
• and
• Z is N or C—R9, wherein R9 is H, halo, or (C1-C6)alkyl;
• and
• where at least one of Q and Z is N.