Substituted quinobenzoxazine analogs

A method for treating or ameliorating a cell proliferative disorder, comprising administering to a subject in need thereof an effective amount of a compound of formula 1

• or a pharmaceutically acceptable salt or a pharmaceutical composition thereof, wherein:
• V is H, halo, NR1R2, NH2, or NR1—(CR12)n—NR3R4;
• A is H, fluoro, or NR12;
• Z is O;
• U is selected from the group consisting of NR1—(CR12)n—NR3R4 and NR1R;
• X is OR2, NR1R2, halo, azido, or SR2;
• n is 1-6;
• R is an optionally substituted 5-14 membered heterocyclic ring containing one or more N, O or S;
• or R is a C1-10 alkyl or C2-10 alkenyl optionally containing one or more non-adjacent heteroatoms selected from N, O, and S, and optionally substituted with an optionally substituted carbocyclic or heterocyclic ring;
• R1 and R3 are independently H or an optionally substituted C1-6 alkyl, said alkyl optionally containing one or more non-adjacent heteroatoms selected from N, O, and S;
• R2 and R4 are independently H or a C1-10 alkyl or C2-10 alkenyl optionally containing one or more non-adjacent heteroatoms selected from N, O, and S, and optionally substituted with an optionally substituted carbocyclic or heterocyclic ring;
• and wherein said C1-10 alkyl may be optionally substituted by one or more OH, C1-6 alkoxy, amino, amido, halo, ═O, aryl or heterocyclic groups;
• or R2 is an optionally substituted heterocyclic ring, aryl or heteroaryl;
• wherein R1 and R2 together with N in NR1R2, and/or R3 and R4 together with N in NR3R4, and/or R1 and R together with N in NR1R may independently form an optionally substituted 5-6 membered ring containing N, and optionally O or S;
• W is selected from the group consisting of
• wherein Q, Q1, Q2, and Q3 are independently CH or N;
• Y is independently O, CH, ═O or NR1;
• and R5 is a substituent at any position on the fused ring;
• and is H, OR2, C1-6 alkyl, or C2-6 alkenyl, each optionally substituted by halo, ═O or one or more heteroatoms;
• or R5 is an inorganic substituent;
• or two adjacent R5 are linked to obtain a 5-6 membered optionally substituted carbocyclic or heterocyclic ring, optionally fused to an additional optionally substituted carbocyclic or heterocyclic ring;
• provided that U is not morpholinyl or 2,4-difluoroaniline when X is F or pyrrolidinyl;
• A is F;
• and W is phenylene;
• wherein said cell proliferative disorder is a cancer selected from colorectal cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, prostate cancer, brain cancer, skin cancer, renal cancer, ovarian cancer, cervical cancer, leukemia, and lymphoma;
• thereby treating or ameliorating said cell-proliferative disorder.