# US 11,306,068 B2 · Oxopiperazine derivatives

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- Number: US 11,306,068 B2
- Document ID: US11306068B2
- Status: Granted
- Kind: B2
- Application number: 16/891,417
- Filed: 2020-06-03
- Published: 2020-10-01
- Granted: 2022-04-19
- Earliest claimed: 2017-12-15
- Assignees: Inthera Bioscience AG
- Applicants: Inthera Bioscience AG
- Inventors: Marc Labelle; Ulrich Kessler; Valentino Cattori; Cyril Cook; Ramkrishna Reddy Vakiti; Kevin R. D. Johnson; Matinder Kaur; Jean-d'amour K. Twibanire; Farman Ullah
- Web page: https://patentgrep.com/patent/US11306068B2

## CPC

- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C07D 401/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 471/10: Spiro-condensed systems
- C07D 491/107: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D 491/113: with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
- C07D 491/20: Spiro-condensed systems
- C07D 495/04: Ortho-condensed systems
- C07D 495/10: Spiro-condensed systems
- C07D 497/10: Spiro-condensed systems
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention relates to novel compounds of formula (I) or formula (Ia) pharmaceutically-acceptable salts, hydrates, solvates, or stereoisomers thereof, and pharmaceutical compositions of these compounds which are useful for preventive and therapeutic use in human and veterinary medicine.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compound is a compound of formula (I)
or a pharmaceutically acceptable salt, hydrate, solvate, or stereoisomer thereof, wherein:
R1 is C1-7 alkyl;
R2 is selected from H, C(O)R14, C(O)OR15, C1-7 alkyl, C3-7 cycloalkyl, C1-5 alkyl-NHCOR13, and C1-3 alkyl substituted by aryl, wherein the aryl is optionally substituted by halogen;
R3 and R7 are each H;
R4 is C1-7 alkyl;
R5 is selected from H, C1-7 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 and C1-7 alkyl;
R8 and RH are each independently selected from H, C1-7 alkyl, and C3-7 cycloalkyl;
X is selected from a bond, C1-7 alkanediyl, —O—C1-7 alkanediyl, and —S—C1-7 alkanediyl; and wherein X can form a ring with any part of R5 or Y;
Y is selected from H, NR10R12, and 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; or Y is heteroaryl, wherein the 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 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;
R10 and R12 are each independently selected from H, C1-7 alkyl, C3-7 cycloalkyl, and C1-3 alkyl-aryl, wherein the alkyl, cycloalkyl, or aryl is optionally substituted by halogen;
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 and C1-7 alkyl; and
each R15 is independently selected from H and C1-7 alkyl.

### Claim 3 (depends on 1)

The method of claim 1, wherein (1) R1 is selected from 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; (2) R2 is selected from H, C(O)R14, C(O)OR15, C1-7 alkyl, C3-7 cycloalkyl, C1-3 alkanediyl-O—C1-3 alkanediyl-O—C1-3 alkanediyl, C1-5 alkyl-OR8, C1-5 alkyl-NHCOR13, and C1-3 alkyl substituted by aryl, wherein the aryl is optionally substituted by halogen, C1-4 alkyl, or C3-5 cycloalkyl; (3) 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; (4) R4 is selected from C1-7 alkyl, C3-7 cycloalkyl, 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; (5) R5 is selected from H, C1-7 alkyl, OR8, and SR8; and wherein C1-7 alkyl, OR8, or SR8 of R5 can form a ring with any part of X or Y, wherein the ring optionally contains a carbonyl group; and/or (6) R6 is selected from H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C3-7 cycloalkyl, and C4-7 cycloalkenyl; or R6 is imidazolidinone.

### Claim 4 (depends on 1)

The method of claim 1, wherein (1) R1 is selected from C3-7 alkyl, C3-7 cycloalkyl, and C1-3 alkyl substituted by aryl or heteroaryl; (2) R2 is selected from H and C(O)R14, wherein R14 is C1-7 alkyl; or R2 is C1-7 alkyl, C3-7 cycloalkyl, C1-5 alkyl-OR8, or C1-5 alkyl-NHCOR13, wherein R13 is pentylamino-5-oxopentyl-7-thia-2.4-diazabicyclo[3.3.0]octan-3-one; or R2 is C1-3 alkyl substituted by aryl, wherein the aryl is optionally substituted by halogen, C1-4 alkyl, or C3-5 cycloalkyl; (3) R3 and R7 are H; and/or (4) R4 is selected from C3-7 alkyl, C3-7 cycloalkyl, and C1-3 alkyl substituted by aryl or heteroaryl.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compound is of any one of Formula (IIa), (IIb), (IIc), (IIIa), (IIIb), (IIIc), (IIId), (IVa), (IVb), (IVc), (IVd), (Va), (Vb), (Vc), (Vd), (VIa), (VIb), (VIc), (VId), (VIIa), (VIIb), (VIIc), (VIId), (VIIe), (VIIf), (VIIIa), (VIIIb), (VIIIc), (VIIId), (VIIIe), (VIIIf), (VIIIg), (VIIIh), (VIIIi), (VIIIj), (VIIIk), (VIIIl), (IXa), (IXb), (IXc), or (IXd):
or a pharmaceutically acceptable salt, hydrate, solvate, or stereoisomer thereof, wherein Q1 and Q2 are each independently O, S, NR8, or CR8; n5 is 0, 1, 2, 3, 4, 5, 6, or 7; n8 is 0, 1, 2, 3, 4, 5, 6, or 7; and n10 is 0, 1, 2, 3, 4, 5, 6, or 7.

### Claim 6 (depends on 1)

The method of claim 1, wherein (1) R8 and R11 are each independently selected from H, C1-7 alkyl, C2-7 alkenyl, and C3-7 cycloalkyl; (2) R9 is selected from H, C1-5 alkyl, halogen, C1-5 alkyl-NR8R11, C1-5 alkyl-C(O)OR8, C1-5 alkyl-C(O)NR8R11, CN, C(O)R8, C(O)NR8R11, C(O)OR8, and OR8; (3) R10 and R12 are each independently selected from H, C1-7 alkyl, C2-7 alkenyl, 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, cycloalkyl, cycloalkenyl, alkanediyl, aryl, or heteroaryl is optionally substituted by halogen or OR8; (4) R14 is selected from C1-7 alkyl, C3-7 cycloalkyl, 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/or (5) each R15 is independently selected from H, C1-7 alkyl, and C3-7 cycloalkyl.

### Claim 7 (depends on 1)

The method of claim 1, wherein (1) X is selected from a bond, C1-7 alkanediyl, —O—, C1-3 alkanediyl-O—, —O—C1-7 alkanediyl, C1-3 alkanediyl-O—C1-7 alkanediyl, C1-7 heteroalkanediyl, and —S—C1-7 alkanediyl; and wherein X can form a ring with any part of R5 or Y, wherein the ring optionally contains a carbonyl group; (2) X is selected from a bond and C1-7 alkanediyl, and wherein C1-7 alkanediyl of X can form a ring with any part of Y; or (3) X is selected from a bond, —O—C1-7 alkanediyl, —S—C1-7 alkanediyl, and C1-7 alkanediyl, wherein —O—C1-7 alkanediyl, —S—C1-7 alkanediyl, or C1-7 alkanediyl of X can form a ring with any part of R5, wherein the ring optionally contains a carbonyl group.

### Claim 8 (depends on 1)

The method of claim 1, wherein (1) Y is selected from H, C(O)NR10R12, C(O)OR10, NR10R12, CN, C3-7-cycloalkyl optionally containing a heteroatom in the ring selected from O and N, wherein if the heteroatom is N the ring 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 when Y is C(O)NR10R12 or NR10R12, 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; (2) Y is selected from H, C(O)NR10R12, C(O)OR10, NR10R12, CN, C3-7-cycloalkyl optionally containing a heteroatom in the ring selected from O and N, wherein if the heteroatom is N the ring 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; (3) Y is selected from C(O)NR10R12, NR10R12, 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 heteroaryl wherein the 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; or (4) Y is selected from NR10R12 and C3-7-cycloalkyl optionally containing a heteroatom in the ring selected from O and N, wherein if the heteroatom is N the ring is optionally substituted by R8; and wherein Y can form a ring with any part of X or R5; with the proviso that when Y is NR10R12, R10 and R12 can form a ring wherein the ring contains 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.

### Claim 9 (depends on 1)

The method of claim 1, wherein (1a) R5 is selected from H and C1-7 alkyl; wherein the C1-7 alkyl of R5 can form a ring with any part of Y; (1b) R5 is selected from C1-7 alkyl, OR8, and SR8; wherein the C1-7 alkyl, OR8, or SR8 of R5 can form a ring with any part of X; or (1c) R5 is OR8, wherein the R8 of OR8 is C1-7 alkyl, and wherein the OR8 of R5 can form a ring with any part of X;
wherein (2a) X is selected from a bond and C1-7 alkanediyl, and wherein the C1-7 alkanediyl of X can form a ring with any part of Y; (2b) X is selected from —O—C1-7 alkanediyl, —S—C1-7 alkanediyl, and C1-7 alkanediyl, and wherein the —O—C1-7 alkanediyl, —S—C1-7 alkanediyl, or C1-7 alkanediyl of X can form a ring with any part of R5; or (2c) X is —O—C1-7 alkanediyl, wherein —O—C1-7 alkanediyl of X can form a ring with any part of R5;
wherein (3a) Y is selected from NR10R12 and C3-7-cycloalkyl optionally containing a heteroatom in the ring wherein the heteroatom is N and is optionally substituted by R8 wherein R8 is C1-7 alkyl;
and wherein Y can form a ring with any part of C1-7 alkanediyl of X or with any part of C1-7 alkyl of R5; with the proviso that when Y is 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; (3b) Y is NR10R12 wherein 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; or (3c) Y is NR10R12 wherein R10 and R12 can form a ring wherein the ring contains the N of NR10R12 and four or five carbon atoms; and
wherein R10 and R12 are each independently selected from H, C1-7 alkyl, C3-7 cycloalkyl, and C1-3 alkyl-aryl, wherein the alkyl, cycloalkyl, or aryl is optionally substituted by halogen.

### Claim 10 (depends on 1)

The method of claim 1, wherein (1) Y is aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted by one or more of R8; or Y is S-heteroaryl, wherein the S-heteroaryl is optionally substituted by one or more R14; (2) Y is C(O)NR10R12; wherein 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; (3) Y is selected from 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; (4) Y is C(O)OR10; (5) Y is H; or (6) Y is CN.

### Claim 11 (depends on 1)

The method of claim 1,
wherein R5 is selected from H and C1-7 alkyl;
X is selected from a bond and C1-7 alkanediyl; and
(1) Y is heteroaryl, wherein the heteroaryl is optionally substituted by one or more of R8;
or Y is S-heteroaryl, wherein the S-heteroaryl is optionally substituted by one or more R14;
(2) Y is C(O)NR10R12 wherein 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, or
R10 and R12 are each independently selected from H, C1-7 alkyl, C2-7 alkenyl, C3-7 cycloalkyl, and C1-3 alkyl-aryl;
(3) Y is selected from O-aryl and O-heteroaryl, wherein the O-aryl or O-heteroaryl is optionally substituted by one or more R9; wherein R9 is selected from H, C1-5 alkyl, halogen, C1-5 alkyl-NR8R11, C1-5 alkyl-C(O)OR8, C1-5 alkyl-C(O)NR8R11, CN, C(O)R8, C(O)NR8R11, C(O)OR8, and OR8; or
(4) Y is C(O)OR10; wherein R10 is selected from H, C1-7 alkyl, C2-7 alkenyl, 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, cycloalkyl, cycloalkenyl, alkanediyl, aryl, or heteroaryl is optionally substituted by OR8.

### Claim 12 (depends on 1)

The method of claim 1, wherein the cancer is a lymphoma, a leukemia, a brain cancer, a nervous system cancer, a breast cancer, a cervical cancer, an ovarian cancer, a colorectal cancer, a stomach cancer, a gastric cancer, a kidney cancer, a liver cancer, a lung cancer, an oesophageal cancer, a pancreatic cancer, a prostate cancer, a colon cancer, a skin cancer, or a head-and-neck cancer.

### Claim 13 (depends on 5)

The method of claim 5, wherein the compound is of Formula (VIc):
or a pharmaceutically acceptable salt, hydrate, solvate, or stereoisomer thereof, wherein n5 is 0, 1, 2, 3, 4, 5, 6, or 7.

### Claim 14 (depends on 5)

The method of claim 5, wherein the compound is of any one of Formula (VIIIi), (VIIIk), or (VIIIl):
or a pharmaceutically acceptable salt, hydrate, solvate, or stereoisomer thereof, wherein Q1 and Q2 are each independently O, S, NR8, or CR8, and wherein R6, R8, and Y are as described herein.

### Claim 15 (depends on 5)

The method of claim 5, wherein the compound is of any one of Formula (IXc) or (IXd):
or a pharmaceutically acceptable salt, hydrate, solvate, or stereoisomer thereof, wherein n10 is 0, 1, 2, 3, 4, 5, 6, or 7, and wherein R6, R10, and R12 are as described herein.

### Claim 16 (depends on 15)

The method of claim 15, wherein the compound is of Formula (IXd):
or a pharmaceutically acceptable salt, hydrate, solvate, or stereoisomer thereof, wherein R6, R10, and R12 are as described herein.

### Claim 17 (depends on 1)

The method of claim 1, wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 17)

The method of claim 17, wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 18)

The method of claim 18, wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 19)

The method according to claim 19, wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.