Novel bifunctional metnase/intnase inhibitors and related compositions and methods of treatment of cancer

A compound of the formula:

• wherein:
• R1 is a C1-C6 hydrocarbon which is optionally substituted, a (CH2)j—C1-C6 ether or thioether group which is optionally substituted, a (CH2)j—C1-C6 acyl group which is optionally substituted, a (CH2)j—NR1R2 group wherein R1 and R2 are each independently H, or a C1-C6 alkyl group optionally substituted with halo or at least one hydroxyl group, an optionally substituted (CH2)n-amide group, an optionally substituted (CH2)n-thioamide group, an optionally substituted (CH2)n-aryl group or an optionally substituted (CH2)n-heterocyclic group;
• Each j is independently 0, 1, 2, 3, 4, 5 or 6, preferably 1, 2 or 3;
• Each n is independently 0, 1, 2, 3, 4, 5, or 6, preferably 0, 1, 2, or 3;
• R2 is H, halo, or an optionally substituted C1-C6 hydrocarbon which is optionally substituted with a —C0-C6-hydrocarbon-NRcRd group, where Rc and Rd are each independently a —(CH2)i—W group where each i is independently 0, 1, 2, 3, 4, 5 or 6 and W is a halo group;
• R3 is H, halo, —N(H)Ra, —N(H)C(═O)Ra, —C(═O)Rb, a
• group or a —C0-C6-hydrocarbon-NRcRd group which is optionally substituted and wherein R2 and R3 are not both H or halo;
• each of i, Rc and Rd is independently the same as described above;
• each RT is independently H or a C1-C3 alkyl group which is optionally substituted with one or two hydroxyl groups;
• each q is independently 0 or 1;
• each v is independently 0 or 1;
• is a first cyclic hydrocarbon group which is optionally substituted;
• is a second cyclic hydrocarbon group which is optionally substituted;
• Ra is
• where Rx is a C1-C6 hydrocarbon which is optionally substituted, an optionally substituted (CH2)j—C1-C6 ether or thioether group, an optionally substituted (CH2)j—C1-C6 acyl group, an optionally substituted (CH2)n-amide group, or an optionally substituted (CH2)n-thioamide group;
• Ry, and R, are each independently, an optionally substituted C1-C6 hydrocarbon, an optionally substituted (CH2)j—C1-C6 ether or thioether group, an optionally substituted (CH2)j—C1-C6 acyl group, a (CH2)j—NR1R2 group wherein R1 and R2 are each independently H, or a C1-C6 alkyl group optionally substituted with halo or at least one hydroxyl group, an optionally substituted (CH2)n-amide group, or an optionally substituted (CH2)n-thioamide group;
• Rb is an optionally substituted aryl, an optionally substituted (C0-C6 hydrocarbon)-aryl, an optionally substituted —O-aryl, an optionally substituted (C0-C6 hydrocarbon)-hetaryl, an optionally substituted —O-hetaryl wherein each Rb group is optionally substituted with one or more substituents, each of which is independently Ra as defined above, halo, C1-C6 hydrocarbon, —C1-C6 haloalkyl, —O—C1-C6 alkyl, —O—C1-C6 haloalkyl, oxo (═O), or —CO2Rm, where Rm is —H or —C1-C6 alkyl which is optionally substituted with at least one hydroxyl group, or Rb may be an optionally substituted C0-C6alkyl-W—X—Z group,
• where W is an optionally substituted carbocyclic aryl or heteroaryl group;
• X is absent, S, O or a —N(RN)— group where RN is H or a C1-C3 alkyl group which is optionally substituted with one or two hydroxyl groups;
• and Z is absent, a carbocyclic aryl or heteroaryl group each of which group is further optionally substituted with one or more substituents, each of which substituent is independently Ra′, halo, C1-C6 hydrocarbon, —C1-C6 haloalkyl, —O—C1-C6 alkyl, —O—C1-C6 haloalkyl, oxo (═O), or —CO2Rm, wherein Ra′ is
• where Rx′ is absent or Rx, and Ry and Rz are the same as described above, or a pharmaceutically acceptable salt, solvate or polymorph thereof.