3,4-Disubstituted coumarin and quinolone compounds

A compound having the formula II:

• wherein:
• each R1 is independently selected from alkyl, alkenyl, alkynyl, aralkyl, —O—R11, —N(R12)(R13), —N(R11)C(O)R11, —N(R11)SO2R11, —SR11, —C(O)R11, —C(O)OR11, —C(O)N(R2)(R13), —OC(O)R11, —OC(O)N(R12)(R13), CN, CF3, NO2, SO2, —SOR11, —SO3R11, —SO2N(R12)(R13), -alkyl-O—R11, cycloalkyl, cycloalkenyl, phosphate, phosphonate, halo, aryl and heteroaryl;
• additionally or alternatively two R1 substituents on adjacent ring atoms my be combined to form a fused 5 or 6-membered ring, wherein the fused 5- or 6-membered ring may contain from 0 to 3 ring heteroatoms and may be further substituted with on or more substituents selected from R1;
• each R11 is independently selected from H, alkyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and heteroaryl;
• each R12 and R13 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R12 and R13 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom,
• n is 0 to 4;
• R2 is selected from the group consisting of aralkyl, aryl, heteroaryl, cycloalkyl and cycloalkenyl;
• R3 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heteroaryl, —(CH2)aC(O)R31, —(CH2)aC(O)N(R32)(R33), (CH2)aC(O)OR31, —(CH2)aC(O)N(R32)(R33), —(CH2)aN(R32)(R33), —CH═N—R34,
• R31 selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• R32 and R33 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R32 and R33 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• R34 is selected from alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• a is 0 to 6;
• X is selected from O and N—R4;
• R4 is selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heteroaryl, —(CH2)bC(O)R41, —(CH2)bC(O)N(R42)(R43), —(CH2)bC(O)OR41, and —(CH2)bC(O)N(R42)(R43),
• each R41 is independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• R42 and R43 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R42 and R43 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• and
• b is 0 to 6;
• or a pharmaceutically acceptable salt or hydrate thereof.

A compound having the formula XIII:

• wherein:
• each R1 is independently selected from alkyl, alkenyl, alkynyl, aralkyl, —O—R11, —N(R12)(R13), —N(R11)C(O)R11, —N(R11)SO2R11, —SR11, —C(O)R11, —C(O)OR11, —C(O)N(R12)(R13), —OC(O)R11, —OC(O)N(R12)(R13), CN, CF3, NO2, SO2, —SOR11, —SO3R11, —SO2N(R12)(R13), -alkyl-O—R11, cycloalkyl, cycloalkenyl, halo, phosphate, phosphonate, aryl and heteroaryl;
• additionally or alternatively two R1 substituents on adjacent ring atoms my be combined to form a fused 5 or 6-membered ring, wherein the fused 5- or 6-membered ring may contain from 0 to 3 ring heteroatoms and may be further substituted with on or more substituents selected from R1;
• each R11 is independently selected from H, alkyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and heteroaryl;
• each R12 and R13 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R12 and R13 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom,
• n is 0 to 4;
• R5 is selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heteroaryl, —(CH2)bC(O)R51, —(CH2)bC(O)N(R52)(R53), and —(CH2)bC(O)OR51;
• each R51 is independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• R52 and R53 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R52 and R53 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• b is 0 to 6;
• R6 is selected from the group consisting of aryl and heteroaryl;
• R7 is selected from the group consisting of aryl, heteroaryl, —C(O)R31, —C(O)N(R32)(R33), —C(O)OR31, —C(O)N(R32)(R33), and —N(R32)(R33),
• R31 selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• and
• R32 and R33 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R32 and R33 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• or a pharmaceutically acceptable salt or hydrate thereof.

A compound having the formula XIV:

• wherein:
• each R1 is independently selected from alkyl, alkenyl, alkynyl, aralkyl, —O—R11, —N(R12)(R13), —N(R11)C(O)R11, —N(R11)SO2R11, —SR11, —C(O)R11, —C(O)OR11, —C(O)N(R12)(R13), —OC(O)R11, —OC(O)N(R12)(R13), CN, CF3, NO2, SO2, —SOR11, —SO11R , —SO2N(R12)(R13), -alkyl-O—R11, cycloalkyl, cycloalkenyl, halo, phosphate, phosphonate, aryl and heteroaryl;
• additionally or alternatively two R1 substituents on adjacent ring atoms my be combined to form a fused 5 or 6-membered ring, wherein the fused 5- or 6-membered ring may contain from 0 to 3 ring heteroatoms and may be further substituted with on or more substituents selected from R1;
• each R11 is independently selected from H, alkyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and heteroaryl;
• each R12 and R13 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R12 and R13 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom,
• n is 0 to 4;
• R3 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heteroaryl, —(CH2)aC(O)R31, —(CH2)aC(O)N(R32)(R33), (CH2)aC(O)OR31, —(CH2)aC(O)N(R32)(R33), —(CH2)aN(R32)(R33), —CH═N—R34,
• R31 selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• R32 and R33 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R32 and R33 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• R34 is selected from alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl
• a is 0 to 6;
• R5 is selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heteroaryl, —(CH2)bC(O)R51, —(CH2)bC(O)N(R52)(R53), and —(CH2)bC(O)OR51;
• each R51 is independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• R52 and R53 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R52 and R53 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• b is 0 to 6;
• each R8 is independently selected from the group consisting of halo, alkyl, CN, NO2, CO2R81, C(O)R81, —O—R81, —N(R82)(R83), —N(R81)C(O)R81, —N(R81)SO2R81, —SR81, —C(O)N(R82)(R83), —OC(O)R81, —OC(O)N(R82′)(R83), SO2, —SOR81, —SO3R81, —SO2N(R82)(R83), cycloalkyl, cycloalkenyl, aryl and heteroaryl;
• each R81 is independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• each R82 and R83 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R82 and R83 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• and
• m is 0 to 5;
• or a pharmaceutically acceptable salt or hydrate thereof.

A compound having the formula XVI:

• wherein:
• each R1 is independently selected from alkyl, alkenyl, alkynyl, aralkyl, —O—R11, —N(R12)(R13), —N(R11)C(O)R11, —N(R11)SO2R11, —SR11, —C(O)R11, —C(O)OR11, —C(O)N(R12)(R13), —OC(O)R11, —OC(O)N(R12)(R13), CN, CF3, NO2, SO2, —SOR11, —SO3R11, —SO2N(R12)(R13), -alkyl-O—R11, cycloalkyl, cycloalkenyl, halo, phosphate, phosphonate, aryl and heteroaryl;
• additionally or alternatively two R1 substituents on adjacent ring atoms my be combined to form a fused 5 or 6-membered ring, wherein the fused 5- or 6-membered ring may contain from 0 to 3 ring heteroatoms and may be further substituted with on or more substituents selected from R1;
• each R11 is independently selected from H, alkyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and heteroaryl;
• each R12 and R13 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R12 and R13 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom,
• n is 0 to 4;
• R2 is selected from the group consisting of aralkyl, aryl, heteroaryl, cycloalkyl and cycloalkenyl;
• R3 is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heteroaryl, —(CH2)aC(O)R31, —(CH2)aC(O)N(R32)(R33), (CH2)aC(O)OR31, —(CH2)aC(O)N(R32)(R33), —(CH2)aN(R32)(R33), —CH═N—R34,
• R31 selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• R32 and R33 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R32 and R33 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• R34 is selected from alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl
• a is 0 to 6;
• R4 is selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heteroaryl, —(CH2)bC(O)R41, —(CH2)bC(O)N(R42)(R43), —(CH2)bC(O)OR41, and —(CH2)bC(O)N(R42)(R43),
• each R41 is independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• R42 and R43 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R42 and R43 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• b is 0 to 6;
• R5 is selected from the group consisting of H, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, heteroaryl, —(CH2)bC(O)R51, —(CH2)bC(O)N(R52)(R53), and —(CH2)bC(O)OR51;
• each R51 is independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• R52 and R53 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and heteroaryl;
• or R52 and R53 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• and
• b is 0 to 6;
• or a pharmaceutically acceptable salt or hydrate thereof.