Oxopiperazine derivatives

A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (Ia)

• or a pharmaceutically acceptable salt, hydrate, solvate, or stereoisomer thereof, wherein:
• R1 is selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, and C1-3 alkyl substituted by cycloalkyl, aryl, or heteroaryl, wherein the cycloalkyl, aryl, or the heteroaryl is optionally substituted by halogen, C1-4 alkyl, or C3-5 cycloalkyl;
• R2 is selected from H, C(O)R14, C(O)NR15R15, C(O)OR15, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, C1-5 alkyl-OR8, C1-3 alkanediyl-O—C1-3 alkanediyl-O—C1-3 alkanediyl, C1-5 alkyl-NHCOR13, and C1-3 alkyl substituted by cycloalkyl, aryl or heteroaryl, wherein the cycloalkyl, aryl, or the heteroaryl is optionally substituted by halogen, C1-4 alkyl or C3-5 cycloalkyl;
• with the proviso that when R2 is C(O)NR15R15, both R15 can form a ring wherein the ring contains the N of NR15R15 and optionally one further heteroatom selected from O and N, wherein if the one further heteroatom is N, the ring is optionally substituted by R8;
• R3 and R7 are each independently selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, and C4-7 cycloalkenyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, or cycloalkenyl is optionally substituted by halogen, OR8, or NR8R11;
• or R3 and R7 are each independently C1-3 alkyl substituted by aryl or heteroaryl, wherein the aryl or the heteroaryl is optionally substituted by halogen, C1-4 alkyl, or C3-5 cycloalkyl;
• R4 is selected from C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, and C1-3 alkyl substituted by cycloalkyl, aryl, or heteroaryl, wherein the cycloalkyl, aryl or the heteroaryl is optionally substituted by halogen, C1-4 alkyl, or C3-5 cycloalkyl;
• R5 is selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, OR8, C1-3 alkyl-OR8, and SR8;
• and wherein R5 can form a ring with any part of X or Y, wherein the ring optionally contains a carbonyl group;
• R6 is selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, and C4-7 cycloalkenyl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, or cycloalkenyl is optionally substituted by halogen, OR8, or NR8R11;
• or R6 is C1-3 alkyl substituted by C(O)NR8R11;
• or R6 is C1-3 alkyl substituted by aryl or heteroaryl, wherein the aryl or the heteroaryl is optionally substituted by halogen, C1-4 alkyl or C3-5 cycloalkyl;
• and wherein R6 can form a ring with any part of X;
• or R6 is imidazolidinone;
• R8 and R11 are each independently selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, and C4-7 cycloalkenyl;
• X is selected from a bond, C1-7 alkanediyl, C2-7 alkenediyl, C2-7 alkynediyl, C3-9 cycloalkanediyl, C4-6 cycloalkenediyl, —O—, C1-3 alkanediyl-O—, —O—C1-7 alkanediyl, —O—C3-9 cycloalkanediyl, C1-3 alkanediyl-O—C1-7 alkanediyl, C1-7 heteroalkanediyl, and —S—C1-7 alkanediyl;
• and wherein X can form a ring or a polycyclic system with any part of R5, R6, or Y, wherein the ring optionally contains a carbonyl group;
• Y is selected from H, C(O)NR10R12, C(O)OR10, R10NC(O)NR10R12, OC(O)R10, OC(O)NR10R12, S(O)nR8 wherein n is 0, 1 or 2, SO2NR10R12, NR10SO2R10, NR10R12, HNCOR8, CN, C3-7-cycloalkyl optionally containing a heteroatom in the ring selected from O and N, wherein if the heteroatom is N it is optionally substituted by R8, S-aryl, O-aryl, S-heteroaryl, and O-heteroaryl, wherein the S-aryl, O-aryl, S-heteroaryl, or O-heteroaryl is optionally substituted by one or more R9 or R14;
• or Y is aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted by one or more of R8;
• and wherein Y can form a ring with any part of X or R5, wherein the ring optionally contains a carbonyl group;
• with the proviso that when Y is C(O)NR10R12 or NR10R12, R10 and R12 can form a ring wherein the ring contains the N of NR10R12 and optionally one further heteroatom selected from O and N, wherein if the one further heteroatom is N, the ring is optionally substituted by R8;
• R9 is selected from H, halogen, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, C3-5 cycloalkyl, C1-5 alkyl-OR8, C1-5 alkyl-SR8, C1-5 alkyl-NR8R11, C1-5 alkyl-C(O)OR8, C1-5 alkyl-C(O)NR8R11, C1-5 alkyl-C(O)R10, CN, C(O)R8, C(O)NR8R11, C(O)OR8, NR8C(O)NR8R11, OC(O)NR8R11, SO2NR8R11, NR8SO2R8, OR8, NR8R11, and S(O)nR8 wherein n is 0, 1 or 2;
• R10 and R12 are each independently selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, C1-3 alkanediyl-O—C1-3 alkanediyl-O—C1-3 alkanediyl, C1-3 alkyl-aryl, and C1-3 alkyl-heteroaryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkanediyl, aryl, or heteroaryl is optionally substituted by halogen, OR8, or NR8R11;
• R13 is C1-5 alkyl substituted by a bicyclic ring optionally comprising at least one heteroatom and a carbonyl group;
• R14 is selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, and C1-3 alkyl substituted by aryl or heteroaryl, wherein the aryl or the heteroaryl is optionally substituted by halogen, C1-4 alkyl, or C3-5 cycloalkyl;
• and
• each R15 is independently selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, OR8, and C1-3 alkyl-OR8.