Substituted indeno[1,2-c]isoquinoline derivatives and methods of use thereof

A compound of the formula

• 17
• or a pharmaceutically acceptable hydrate or salt thereof,
• wherein:
• R5 is O, NH or S;
• R6 is —H or C1-C4 alkyl;
• X is —CH2—, —CH(halo)-, —CH(OH)(CH2)n—, —CH(OH)-arylene-, —O—, —NH—, —S— or —CH(NR11R12)—, wherein n is an integer ranging from 0-5;
• R11 and R12 are independently -hydrogen or —C1-C9 alkyl, or N, R11 and R12 are taken together to form a heterocyclic amine.
• R1, R2, R3, R4, R7, R8, R9 and R10 are independently -hydrogen, -halo, -hydroxy, —O—(C1-C5 alkyl), —C1-C10 alkyl, -alkylhalo, —C2-C10 alkenyl, —C3-C8 carbocycle, -aryl, —NH2, -alkylamino, —C(O)OH, —C(O)O(C1-C5 alkyl), —OC(O)(C1-C5 alkyl), NO2 or -A-B;
• wherein A is —SO2—, —SO2NH—, —NHCO—, —NHCONH—, —O—, —CO—, —OC(O)—, —C(O)O—, —CONH—, —CON(C1-C4 alkyl)-, —NH—, —CH2—, —S— or —C(S)—;
• B is —C1-C10 alkyl, —C2-C10 alkenyl, -heterocycle, —C3-C, carbocycle, -aryl, —NZ]Z2, -alkylamino, -aminodialkyl, -alkylheterocycle, -arylamido, —C(O)OH, —C(O)O—(C1-C5 alkyl) or —C(O)O-phenyl, any of which are unsubstituted or substituted with one or more of —O—(C1-C5 alkyl), -halo, -alkylhalo, -alkanol, -alkylamino, -hydroxy, —NO2, —NH2, -aminoalkyl, -aminodialkyl, -heterocyclic amine, —C1-C10 alkyl, —C2-C10 alkenyl, —C2-C10 alkynyl, -aryl, -benzyl, -alkylamido, -alkylcarboxy, —C1-C, alkylene-C(O)O—C1-C5 alkyl or —C1-C5 alkylene-OC(O)—C1-C, alkyl groups;
• and
• Z1 and Z2 are independently —H or —C1-C10 alkyl, which is unsubstituted or substituted with one or more of -halo, —OH or —N(Z3)(Z4), where Z3 and Z4 are independently, —H or —C1-C5 alkyl, which is unsubstituted or substituted with one or more of -halo, -hydroxy or —NH2;
• or N, Z3 and Z4 are taken together to form an unsubstituted or substituted heterocyclic amine;
• or N, Z1 and Z2 are taken together to form a heterocyclic amine.

A compound of the formula

• 18
• or a pharmaceutically acceptable hydrate or salt thereof,
• wherein:
• R6 is —H or C1-C4 alkyl;
• R1, R2, R3, R4R7, R8, R9 and R10 are independently -hydrogen, -halo, -hydroxy, —O—(C1-C5 alkyl), —C1-C10 alkyl, -alkylhalo, —C2-C10 alkenyl, —C3-C8 carbocycle, -aryl, —NH2, -alkylamino, —C(O)OH, —C(O)O(C1-C5 alkyl), —OC(O)(C1-C5 alkyl), NO2 or -A-B;
• wherein at least one of R1, R4 and R10 is other than hydrogen;
• A is —SO2—, —SO2NH—, —NHCO—, —NHCONH—, —O—, —CO—, —OC(O)—, —C(O)O—, —CONH—, —CON(C1-C4 alkyl)-, —NH—, —CH2—, —S— or —C(S)—;
• B is —C1-C10 alkyl, —C2-C10 alkenyl, -heterocycle, —C3-C8 carbocycle, -aryl, —NH2, -alkylamino, -aminodialkyl, -alkylheterocycle, -arylamido, —C(O)OH, —C(O)O—(C1-C5 alkyl), —C(O)O-phenyl or —NZ1Z2;
• and
• Z1 and Z2 are independently —H or —C1-C10 alkyl, which is unsubstituted or substituted with one or more of -halo, —OH or —N(Z3)(Z4), where Z3 and Z4 are independently, —H or —C1-C5 alkyl, which is unsubstituted or substituted with one or more of -halo, -hydroxy or —NH2;
• or N, Z3 and Z4 are taken together to form an unsubstituted or substituted heterocyclic amine;
• or N, Z1 and Z2 are taken together to form a heterocyclic amine.

A compound of the formula

• 19
• or a pharmaceutically acceptable hydrate or salt thereof,
• wherein:
• X is —CH2— or —O—;
• R2 and R3 are independently -hydrogen, -halo, -alkylhalo, -hydroxy, —O—(C1-C5 alkyl), —C1-C3 alkyl, —NO2, —NH2, —CONH2, —C(O)OH, —OC(O)—C1-C5 alkyl or —C(O)O—C1-C5 alkyl;
• R8 and R9 are independently -hydrogen and -A-B;
• A is —SO2—, —SO2NH— or —NHCO—;
• and
• B is —C1-C3 alkyl, —NZ1Z2, -heterocycle or -alkylamino, each unsubstituted or substituted with one or more of -alkanol, -alkylamino, -aminoalkyl, -aminodialkyl or -heterocycle, each unsubstituted or substituted with —C1-C10 alkyl or -alkanol;
• and
• Z1 and Z2 are independently -hydrogen or —C1-C8 alkyl, which is unsubstituted or substituted with one or more of -hydroxy or —NZ3Z4, where Z3 and Z4 are independently —H or —C1-C3 alkyl, which is unsubstituted or substituted with one or more of -hydroxy or —NH2, or N, Z3 and Z4 are taken together to a heterocyclic amine, or N, Z1 and Z2 are taken together to form a heterocyclic amine.