Combination therapy of tetracyclic quinolone analogs for treating cancer

The pharmaceutical combination of claim 25, wherein the at least one anti-angiogenic is selected from one or more of the group consisting of 2-methoxyestradiol, AG3340, prinomastat, batimastat, BAY 12-9566, carboxyamidotriazole, CC-1088, dextromethorphan acetic acid, dimethylxanthenone acetic acid, EMD 121974, endostatin, IM-862, marimastat, matrix metalloproteinase, penicillamine, PTK787/ZK 222584, RPI.4610, squalamine, squalamine lactate, 3-[2,4-dimethylpyrrol-5-yl-methyl-idenyl]-2-indolinone (SU5416), (±)-thalidomide, S-thalidomide, R-thalidomide, 0-(chloroacetylcarbamoyl)fumagillol (TNP-470), combretastatin, paclitaxel, tamoxifen, COL-3, neovastat, BMS-275291, SU6668, 2-ME, interferon-alpha, anti-VEGF antibody, Medi-522 (Vitaxin II), CAI (inhibitor of calcium influx), celecoxib, Interleukin-12, IM862, amilloride, Angiostatin® protein, angiostatin K1-3, angiostatin K1-5, captopril, DL-alpha-difluoromethylornithine, DL-alpha-difluoromethylornithine HCl, His-Tag® Endostatin™ Protein, fumagillin, herbimycin A, 4-hydroxyphenylretinamide, gamma-interferon, juglone, laminin, laminin hexapeptide, laminin pentapeptide, lavendustin A, medroxyprogesterone, medroxyprogesterone acetate, minocycline, minocycline HCl, placental ribonuclease inhibitor, suramin, sodium salt Suramin, human platelet thrombospondin, tissue inhibitor of metalloproteinase 1, neutrophil granulocyte tissue inhibitor of metalloproteinase 1, or rheumatoid synovial fibroblast tissue inhibitor of metalloproteinase 2.

A method for treating or ameliorating cell proliferation disorder in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I);

• or a pharmaceutically acceptable salt, ester, solvate and/or prodrug thereof;
• wherein:
• X1 is CH or N;
• X2, X3, X4, X5, X6 and X7 independently are NR4, CH2, CHQ or C(Q)2, provided that zero, one or two of X2, X3, X4, X5, X6 and X7 are NR4;
• A and V independently are H, halo, azido, —CN, —CF3, —CONR1R2, —NR1R2, —SR2, —OR2, or —R3;
• each Q is independently halo, azido, —CN, —CF3, —CONR1R2, —NR1R2, —SR2, —OR2, or —R3;
• in each —NR1R2, R1 and R2 together with N may form an optionally substituted azacyclic ring, optionally containing one additional heteroatom selected from N, O and S as a ring member;
• R1 is H or C1-C6 alkyl, optionally substituted with one or more halogens, or ═O;
• R2 is H, or C1-C10 alkyl, C1-C10 heteroalkyl, C2-C10 alkenyl, or C2-C10 heteroalkenyl, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-7 membered carbocyclic or heterocyclic ring;
• R3 is an optionally substituted C1-C10 alkyl, C2-C10 alkenyl, C5-C10 aryl, or C6-C12 arylalkyl, or a heteroform of one of these, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-6 membered carbocyclic or heterocyclic ring;
• each R4 is independently H, or C1-C6 alkyl;
• R7 is H and R8 is C1-C10 alkyl, C1-C10 heteroalkyl, C2-C10 alkenyl, or C2-C10 heteroalkenyl, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-7 membered carbocyclic or heterocyclic ring;
• or in —NR7R8, R7 and R8 together with N may form an optionally substituted azacyclic ring, optionally containing an additional heteroatom selected from N, O and S as a ring member;
• m is 0, 1, 2, 3 or 4;
• n is 0, 1, 2, 3, 4, or 5;
• and administering radiotherapy or at least one additional therapeutically active agent before, during, or after the subject has been administered a compound of formula (I).