PARP7 inhibitor for preventing or treating tumors

Abstract

A PARP7 inhibitor for treating and / or preventing tumors.

Description

PARP7 inhibitors for preventing or treating tumors Technical Field

[0001] The present invention belongs to the field of medicine, and in particular relates to a PARP7 inhibitor for preventing or preparing tumors. Background Art

[0002] Cancer is a major disease that affects human health and has become one of the most common diseases. As a core event in tumor evolution, the heterogeneity and dynamic characteristics of tumors pose severe challenges to tumor treatment; at the same time, the interaction and dynamic changes between tumors and the microenvironment make tumor treatment more complex and difficult. In the drug treatment of tumors, chemotherapy is one of the commonly used methods, but due to its low specificity, large adverse reactions, easy to develop drug resistance with long-term use, high mortality, recurrence and metastasis, etc., cancer patients bear a heavy disease burden and there are huge unmet needs. Therefore, new treatment methods are urgently needed.

[0003] 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly (ADP-ribose) polymerase (PARP7) is a member of the MonoPARP family. TCDD activates the aryl hydrocarbon receptor (AHR) and upregulates its expression. Summary of the Invention

[0004] One or more embodiments of the present application provide PARP7 inhibitors as active ingredients for treating and / or preventing cancer or tumors, so as to overcome the deficiencies of the prior art.

[0005] One or more embodiments of the present application provide use of a PARP7 inhibitor in the preparation of a medicament for treating and / or preventing cancer or tumors.

[0006] One or more embodiments of the present application provide the PARP7 inhibitor of the present application, which is used as a drug.

[0007] One or more embodiments of the present application provide the PARP7 inhibitor of the present application, which is used for treating and / or preventing cancer or tumors.

[0008] One or more embodiments of the present application provide a method for treating and / or preventing cancer or tumors, comprising administering a therapeutically or preventively effective amount of the PARP7 inhibitor of the present application to a subject in need thereof.

[0009] In one or more embodiments of the present application, the PARP7 inhibitor of the present application is or a pharmaceutically acceptable salt thereof.

[0010] In one embodiment, the PARP7 inhibitor is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound represented by formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof:

[0011] in:

[0012] X1 is NH, O or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0013] X2 is O or a single bond;

[0014] X3 and X4 are each independently C or N;

[0015] R 1a 、R 1b Each independently is H, D or C 1-6 Alkyl; or R 1a 、R 1b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group;

[0016] R 2a 、R 2b Each independently is H, D or C 1-6 Alkyl; or R 2a 、R 2b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group;

[0017] R3 is H, D, C 1-6 Alkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0018] R4 and R5 are each independently H, D or C 1-6 Alkyl; or R4, R5 and the connected carbon atom form a 3 to 5-membered cycloalkyl;

[0019] R6 and R7 are each independently H, D or C 1-6 Alkyl; or R6, R7 and the connected carbon atom form C=O;

[0020] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the carbon atom to which they are connected form C=O; or R8 and R9 and the carbon atom to which they are connected form a 3- to 5-membered cycloalkyl;

[0021] R 10 Each independently is C 1-6 Alkyl, C 1-6 Alkoxy, CONR 10aR 10b , halogen, cyano, S(O)2R 10c SR 10d or a 3 to 5-membered cycloalkyl group, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0022] R 10a 、R 10b 、R 10c 、R 10d Each independently is H, D or C 1-6 alkyl;

[0023] A is R a C 1-6 Alkyl, C 3-5 Cycloalkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0024] B is a 5- to 10-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0025] C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms;

[0026] m is 1, 2, or 3;

[0027] n is 0, 1, 2, or 3:

[0028] p is 0, 1, 2 or 3.

[0029] In one or more embodiments:

[0030] X1 is NH, O or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0031] X2 is O or a single bond;

[0032] X3 and X4 are each independently C or N;

[0033] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0034] R 2a 、R 2b Each independently is H, D or C 1-6 Alkyl; or R 2a 、R 2b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group;

[0035] R3 is H, D, C1-6 Alkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0036] R4 and R5 are each independently H, D or C 1-6 Alkyl; or R4, R5 and the connected carbon atom form a 3 to 5-membered cycloalkyl;

[0037] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0038] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O;

[0039] R 10 Each independently is C 1-6 Alkyl, C 1-6 Alkoxy, CONR 10a R 10b , halogen, cyano, S(O)2R 10c SR 10d or a 3 to 5-membered cycloalkyl group, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0040] R 10a 、R 10b 、R 10c 、R 10d Each independently is H, D or C 1-6 alkyl;

[0041] A is R a C 1-6 Alkyl, C 3-5 Cycloalkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0042] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0043] C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms;

[0044] m is 1, 2, or 3;

[0045] n is 0, 1, 2, or 3;

[0046] p is 0, 1, 2 or 3.

[0047] In one or more embodiments, the compound represented by formula (I) has the structure of formula (I-1):

[0048] in

[0049] X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0050] X2 is 0;

[0051] X3 and X4 are each independently C or N;

[0052] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0053] R 2a 、R 2b Each independently is H, D or C 1-6 alkyl;

[0054] R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0055] R4 and R5 are each independently H, D or C 1-6 alkyl;

[0056] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0057] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8 and R9 form C=O with the carbon atom to which they are connected;

[0058] R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0059] R 10d H, D or C 1-6 alkyl;

[0060] A is

[0061] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0062] C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms;

[0063] m is 1, 2, or 3;

[0064] n is 0, 1, 2 or 3.

[0065] In one or more embodiments, the compound represented by formula (I) has the structure of formula (I-2):

[0066] in:

[0067] X1 is NH;

[0068] X2 is 0;

[0069] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0070] R 2a 、R 2b Each independently is H, D or C 1-6 alkyl;

[0071] R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0072] R4 and R5 are each independently H, D or C 1-6 alkyl;

[0073] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0074] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8 and R9 and the carbon atom to which they are attached form C=O;

[0075] R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0076] R 10d H, D or C 1-6 alkyl;

[0077] A is

[0078] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0079] m is 1, 2, or 3:

[0080] n is 0, 1, 2 or 3.

[0081] In one or more embodiments:

[0082] X1 is NH;

[0083] X2 is 0;

[0084] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0085] R 2a 、R 2b Each independently is H, D or C 1-6 alkyl;

[0086] R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0087] R4 and R5 are each independently H, D or C 1-6 alkyl;

[0088] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0089] R8 and R9 are each independently H, D or C 1-6 Alkyl, or R8 and R9 form C=O with the carbon atom to which they are connected;

[0090] R 10 C 1-6 Alkyl, cyano, or SR 10d , the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0091] R 10d H, D or C 1-6 alkyl;

[0092] A is

[0093] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0094] m is 1, 2, or 3;

[0095] n is 0, 1, 2 or 3.

[0096] In one or more embodiments:

[0097] X1 is selected from NH;

[0098] X2 is selected from O;

[0099] R 1a 、R 1b Each independently selected from H, D or C 1-6 alkyl;

[0100] R 2a 、R 2b Each independently selected from H, D or C 1-6 alkyl;

[0101] R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0102] R4 and R5 are each independently H or D;

[0103] R6 and R7 are each independently H or D;

[0104] R8 and R9 are each independently H or D;

[0105] R 10 CF3 or SR 10d ;

[0106] R 10d H, D or C 1-6 alkyl;

[0107] A is

[0108] B is

[0109] m is 1, 2, or 3;

[0110] n is 0, 1, 2 or 3.

[0111] In one or more embodiments:

[0112] X1 is selected from NH;

[0113] X2 is selected from O;

[0114] R 1a 、R 1b Each independently selected from H, D or C 1-3 alkyl;

[0115] R 2a 、R 2bEach independently selected from H, D or C 1-3 alkyl;

[0116] R3 is selected from H, D or CF3;

[0117] R4 and R5 are each independently selected from H or D;

[0118] R6 and R7 are each independently selected from H or D;

[0119] R8 and R9 are each independently selected from H or D;

[0120] R 10 is CF3;

[0121] A is

[0122] B is

[0123] m is 1, 2, or 3;

[0124] n is 0, 1 or 2.

[0125] In one or more embodiments, the compound represented by formula (I) has the structure of formula (I-3):

[0126] in:

[0127] X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0128] X2 is 0;

[0129] R 1a 、R 1b Each independently is H, D or C 1-6 alkyl;

[0130] R 2a 、R 2b Each independently is H, D or C 1-6 alkyl;

[0131] R4 and R5 are each independently H, D or C 1-6 alkyl;

[0132] R6 and R7 are each independently H, D or C 1-6 alkyl;

[0133] R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O;

[0134] R 10 C 1-6Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens;

[0135] R 10d H, D or C 1-6 alkyl;

[0136] A is

[0137] B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S;

[0138] m is 1, 2, or 3;

[0139] n is 0, 1, 2 or 3.

[0140] In one or more embodiments:

[0141] X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O;

[0142] X2 is 0;

[0143] R 1a 、R 1b Each independently is H, D or C 1-3 alkyl;

[0144] R 2a 、R 2b Each independently is H, D or C 1-3 alkyl;

[0145] R4 and R5 are each independently H, D or C 1-3 alkyl;

[0146] R6 and R7 are each independently H, D or C 1-3 alkyl;

[0147] R8 and R9 are each independently H, D or C 1-3 Alkyl; or R8 and R9 form C=O with the carbon atom to which they are connected;

[0148] R 10 C 1-6 Alkyl, cyano or SR 10d , the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens;

[0149] R 10d H, D or C 1-6 alkyl;

[0150] A is

[0151] B is

[0152] m is 1, 2, or 3;

[0153] n is 0, 1 or 2.

[0154] In one or more embodiments:

[0155] X1 is NH;

[0156] X2 is 0;

[0157] R 1a 、R 1b Each independently is H, D or C 1-3 alkyl;

[0158] R 2a 、R 2b Each independently is H or D;

[0159] R4 and R5 are each independently H or D;

[0160] R6 and R7 are each independently H or D;

[0161] R8 and R9 are each independently H or D;

[0162] R 10 is CF3;

[0163] A is

[0164] B is

[0165] m is 1, 2, or 3:

[0166] n is 0, 1 or 2.

[0167] In one or more embodiments, the PARP7 inhibitor is the following compound:

[0168] In one or more embodiments, the PARP7 inhibitor is contained in a pharmaceutical composition that further comprises one or more pharmaceutically acceptable excipients, diluents, or carriers.

[0169] In one or more embodiments, the tumor is selected from solid tumors and / or hematological tumors.

[0170] In one or more embodiments, the tumor is selected from malignant solid tumors.

[0171] In one or more embodiments, the tumor is selected from advanced malignant solid tumors.

[0172] In one or more embodiments, the solid tumor is selected from colorectal cancer, breast cancer, central nervous system cancer, uterine cancer, cervical cancer, kidney cancer, adrenal cancer, lung cancer, esophageal cancer, head and neck cancer, ovarian cancer, pancreatic cancer, liver cancer, prostate cancer, endometrial cancer, testicular cancer, gastric cancer, laryngeal cancer, urinary tract cancer, bladder cancer, colon cancer, rectal cancer, thyroid cancer, bone cancer, epithelial cancer, bile duct cancer, gallbladder cancer, skin cancer, mesothelioma, basal cell carcinoma, adenoid cystic carcinoma, leiomyosarcoma, gastrointestinal stromal tumor, Ewing sarcoma, Kaposi sarcoma, or a PARP7-amplified advanced solid tumor.

[0173] In one embodiment, the hematological tumor is selected from the group consisting of leukemia, myeloma, and lymphoma.

[0174] In one embodiment, the hematological neoplasm is selected from Hodgkin's lymphoma or non-Hodgkin's lymphoma, multiple myeloma, B-cell lymphoma, small lymphocytic lymphoma, T-cell lymphoma, hairy cell lymphoma, Burkett's lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia.

[0175] In one or more embodiments, the lung cancer is non-small cell lung cancer or neuroendocrine lung cancer.

[0176] In one or more embodiments, the non-small cell lung cancer is lung squamous cell carcinoma or lung adenocarcinoma.

[0177] In one or more embodiments, the breast cancer is selected from hormone receptor positive (HR+) breast cancer.

[0178] In one or more embodiments, the head and neck cancer is selected from head and neck squamous cell carcinoma.

[0179] In one or more embodiments, the uterine cancer is selected from endometrial cancer.

[0180] In one or more embodiments, the central nervous system cancer is glioma.

[0181] In one or more embodiments, the liver cancer is hepatocellular carcinoma.

[0182] In one embodiment, the B-cell lymphoma is preferably diffuse large B-cell lymphoma.

[0183] In one or more embodiments, the daily dose of the PARP7 inhibitor is 50 to 2000 mg / day.

[0184] In one or more embodiments, the daily dose of the PARP7 inhibitor is 100-1500 mg / day.

[0185] In one or more embodiments, the daily dose of the PARP7 inhibitor is 200-1000 mg / day.

[0186] In one embodiment, the PARP7 inhibitor is administered three times a day, twice a day, once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, or once every four weeks.

[0187] In one or more embodiments, the PARP7 inhibitor is administered twice a day or once a day.

[0188] In one or more embodiments, the daily dose of the PARP7 inhibitor is 25-100 mg BID.

[0189] In one or more embodiments, the daily dose of the PARP7 inhibitor is 50-750 mg BID.

[0190] In one or more embodiments, the daily dose of the PARP7 inhibitor is 100-500 mg BID.

[0191] In one or more embodiments, the total daily dose of the PARP7 inhibitor is selected from 50-1500 mg, such as 100-1000 mg, measured as the free base.

[0192] In one or more embodiments, the PARP7 inhibitor is administered orally at a frequency of three times a day, twice a day, once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, once every four weeks, for example, twice a day or once a day.

[0193] Unless stated otherwise, the terms used in the specification and claims have the following meanings.

[0194] The carbon, hydrogen, oxygen, sulfur, nitrogen or F, Cl, Br, I involved in the groups and compounds described in this application include their isotopes, and the carbon, hydrogen, oxygen, sulfur or nitrogen involved in the groups and compounds described in this application are optionally further replaced by one or more of their corresponding isotopes, wherein the isotopes of carbon include 12 C. 13 C and 14 C, oxygen isotopes include 16 O. 17 O and18 O, sulfur isotopes include 32 S. 33 S. 34 S and 36 S, nitrogen isotopes include 14 N and 15 N, fluorine isotopes include 17 F and 19 F, chlorine isotopes include 35 Cl and 37 Isotopes of Cl, bromine include 79 Br and 81 Br.

[0195] "Alkyl" refers to a linear or branched saturated aliphatic hydrocarbon group of 1 to 20 carbon atoms, preferably an alkyl group of 1 to 8 (e.g., 1, 2, 3, 4, 5, 6, 7, 8) carbon atoms, more preferably an alkyl group of 1 to 6 carbon atoms, and even more preferably an alkyl group of 1 to 4 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, neobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, and various branched isomers thereof; when an alkyl group is substituted, it may optionally be further substituted with one or more substituents.

[0196] "Alkoxy" refers to a group in which at least one carbon atom in an alkyl group is replaced by an oxygen atom. Non-limiting examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexyloxy, cyclopropyloxy, and cyclobutyloxy. The definition of "alkyl" is the same as that of "alkyl" described above.

[0197] "Alkenyl" refers to a straight-chain or branched unsaturated aliphatic hydrocarbon group consisting of 2 to 20 carbon atoms and containing 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10) carbon-carbon double bonds, preferably an alkenyl group of 2 to 12 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) carbon atoms, more preferably an alkenyl group of 2 to 8 carbon atoms, and further preferably an alkenyl group of 2 to 6 carbon atoms. Non-limiting examples include ethenyl, propen-2-yl, buten-2-yl, buten-2-yl, penten-2-yl, penten-4-yl, hexen-2-yl, hexen-3-yl, hepten-2-yl, hepten-3-yl, hepten-4-yl, octen-3-yl, nonen-3-yl, decen-4-yl, and undecen-3-yl. The alkenyl group may be optionally further substituted by one or more substituents.

[0198] "Alkynyl" refers to a straight-chain or branched unsaturated aliphatic hydrocarbon group consisting of 2 to 20 carbon atoms and containing 1 to 10 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) carbon-carbon triple bonds, preferably an alkynyl group of 2 to 12 (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12) carbon atoms, more preferably an alkynyl group of 2 to 8 carbon atoms, and even more preferably an alkynyl group of 2 to 6 carbon atoms. Non-limiting examples include ethynyl, propyn-1-yl, propyn-2-yl, butyn-1-yl, butyn-2-yl, butyn-3-yl, 3,3-dimethylbutyn-2-yl, pentyn-1-yl, pentyn-2-yl, hexyn-1-yl, 1-heptyn-1-yl, heptyn-3-yl, heptyn-4-yl, octyn-3-yl, nonyn-3-yl, decyn-4-yl, undecyne-3-yl, dodecyne-4-yl. The alkynyl group may optionally be further substituted with one or more substituents.

[0199] "Aryl" refers to a substituted or unsubstituted aromatic ring, which can be a 5-8 membered (e.g., 5, 6, 7, 8 membered) monocyclic ring, a 5-12 membered (e.g., 5, 6, 7, 8, 9, 10, 11, 12 membered) bicyclic ring, or a 10-15 membered (e.g., 10, 11, 12, 13, 14, 15 membered) tricyclic ring system, which can be a bridged ring or a spirocyclic ring, non-limiting examples of which include phenyl and naphthyl. The aryl group may optionally be further substituted with one or more substituents.

[0200] "Heteroaryl" refers to a substituted or unsubstituted aromatic ring, which can be a 3-8 membered (e.g., 3, 4, 5, 6, 7, 8 membered) monocyclic ring, a 5-12 membered (e.g., 5, 6, 7, 8, 9, 10, 11, 12 membered) bicyclic ring or a 10-15 membered (e.g., 10, 11, 12, 13, 14, 15 membered) tricyclic ring system, and contains 1 to 6 (e.g., 1, 2, 3, 4, 5, 6) heteroatoms selected from N, O or S, preferably a 5- to 8-membered heteroaryl group, and the 1 to 4 (e.g., 1, 2, 3, 4) N and S optionally substituted in the heteroaryl ring can be oxidized to various oxidation states. The heteroaryl group can be attached to a heteroatom or a carbon atom. The heteroaryl group can be a bridged ring or a spirocyclic ring. Non-limiting examples include cyclic pyridyl, furyl, thienyl, pyranyl, pyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, piperidinylbenzimidazolyl, benzopyridinyl, pyrrolopyridinyl. The heteroaryl group is optionally further substituted with one or more substituents.

[0201] "Carbocyclyl" or "carbocycle" refers to a saturated or unsaturated aromatic or non-aromatic ring. When it is an aromatic ring, its definition is the same as the definition of "aryl" above; when it is a non-aromatic ring, it can be a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, 10-membered) monocyclic ring, a 4- to 12-membered (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12-membered) bicyclic ring, or a 10- to 15-membered (e.g., 10, 11, 12, 13, 14, 15-membered) tricyclic ring system, which can be a bridged ring or a spirocyclic ring. Non-limiting examples include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopentyl-1-enyl, 1-cyclopentyl-2-enyl, 1-cyclopentyl-3-enyl, cyclohexyl, 1-cyclohexyl-2-enyl, 1-cyclohexyl-3-enyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, and cyclododecyl.

[0202] The "carbocyclyl" or "carbocycle" may be further substituted by one or more substituents.

[0203] "Heterocyclyl" or "heterocycle" refers to a saturated or unsaturated aromatic heterocycle or non-aromatic heterocycle. When it is an aromatic heterocycle, its definition is the same as the above "heteroaryl"; when it is a non-aromatic heterocycle, it can be a 3-10 membered (e.g., 3, 4, 5, 6, 7, 8, 9, 10 membered) monocyclic ring, a 4-12 membered (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12 membered) bicyclic ring or a 10-15 membered (e.g., 10, 11, 12, 13, 14, 15 membered) tricyclic ring system, and contains 1 to 4 (e.g., 1, 2, 3, 4) heteroatoms selected from N, O or S, and is preferably a 3- to 8-membered heterocyclyl. The 1 to 4 (e.g., 1, 2, 3, 4) N, S optionally substituted in the ring of "heterocyclyl" or "heterocycle" can be oxidized to various oxidation states; "heterocyclyl" or "heterocycle" can be attached to a heteroatom or a carbon atom; "heterocyclyl" or "heterocycle" can be a bridged ring or a spirocycle. Non-limiting examples of "heterocyclyl" or "heterocycle" include oxirane, glycidyl, aziridine, oxetanyl, azetidinyl, thietanyl, 1,3-dioxolanyl, 1,4-dioxolanyl, 1,3-dioxhexacyclyl, azepanyl, oxetanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, pyridyl, homopiperidinyl, furanyl, thienyl, pyranyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperazinyl, homopiperazinyl, imidazolyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, 1,3-dithianyl, dihydrofuranyl, dithiolanyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyridinyl, tetrahydrothiopyranyl, tetrahydropyrrolyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydropyranyl, benzimidazolyl, benzopyridinyl, Pyrrolopyridinyl, pyrazolopyrimidinyl, imidazopyrazinyl, benzodihydrofuranyl, 2-pyrrolinyl, 3-pyrrolinyl, dihydroindolinyl, 2H-pyranyl, 4H-pyranyl, dioxane, 1,3-dioxolane, pyrazolinyl, dithianyl, dithiolanyl, dihydrothienyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, 1,2,3,4-tetrahydroisoquinolinyl, 3-azabicyclo [3.1.0]hexyl, 3-azabicyclo[4.1.0]heptyl, azabicyclo[2.2.2]hexyl, 3H-indolylquinolizinyl, N-pyridylurea, 1,1-dioxothiomorpholinyl, azabicyclo[3.2.1]octanyl, azabicyclo[5.2.0]nonyl, oxatricyclo[5.3.1.1]dodecyl, azaadamantyl and oxaspiro[3.3]heptanyl. The "heterocyclyl" or "heterocycle" may be further substituted with one or more substituents.

[0204] "Cycloalkyl" refers to a saturated cyclic hydrocarbon group, which can be a 3- to 10-membered (e.g., 3, 4, 5, 6, 7, 8, 9, 10-membered) monocyclic ring, a 4- to 12-membered (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12-membered) bicyclic ring, or a 10- to 20-membered (e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20-membered) polycyclic ring system, preferably having 3 to 10 carbon atoms, more preferably 3 to 8 carbon atoms. Non-limiting examples of "cycloalkyl" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, 1,5-cyclooctadienyl, 1,4-cyclohexadienyl, and cycloheptatrienyl. When a cycloalkyl group is substituted, it may be optionally further substituted with one or more substituents.

[0205] "Heterocycloalkyl" refers to a substituted or unsubstituted saturated non-aromatic ring group, which can be a 3-8 membered (e.g., 3, 4, 5, 6, 7, 8 membered) monocyclic ring, a 4-12 membered (e.g., 4, 5, 6, 7, 8, 9, 10, 11, 12 membered) bicyclic ring, or a 10-15 membered (e.g., 10, 11, 12, 13, 14, 15 membered) tricyclic ring system, and contains 1, 2, or 3 heteroatoms selected from N, O, or S, preferably a 3- to 8-membered heterocyclic ring. The 1, 2, or 3 N or S atoms optionally substituted in the "heterocycloalkyl" ring can be oxidized to various oxidation states; the "heterocycloalkyl" can be attached to a heteroatom or a carbon atom; the "heterocycloalkyl" can be a bridged ring or a spirocyclic ring. Non-limiting examples of “heterocycloalkyl” include oxiranyl, aziridinyl, oxetanyl, azetidinyl, 1,3-dioxolanyl, 1,4-dioxolanyl, 1,3-dioxanyl, azepanyl, piperidinyl, piperidinyl, morpholinyl, thiomorpholinyl, 1,3-dithianyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydroimidazolyl, tetrahydrothiazolyl, tetrahydropyranyl, azabicyclo[3.2.1]octanyl, azabicyclo[5.2.0]nonanyl, oxatricyclo[5.3.1.1]dodecyl, azaadamantyl, and oxaspiro[3.3]heptanyl.

[0206] When the above-mentioned "alkyl", "alkoxy", "alkenyl", "alkynyl", "aryl", "heteroaryl", "carbocyclyl", "carbocycle", "heterocyclyl", "heterocycle", "cycloalkyl", "heterocycloalkyl" or "heterocyclyl" is substituted, it may be further substituted by 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 groups selected from F, Cl, Br, I, hydroxyl, mercapto, nitro, cyano, amino, C 1-6 Alkylamino, =O, C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, -NR q4 Rq5 、=NR q6 、-C(=O)OC 1-6 Alkyl, -OC(=O)C 1-6 Alkyl, -C(=O)NR q4 R q5 、C 3-8 Cycloalkyl, C 3-8 Heterocycloalkyl, C 6-10 Aryl, C 5-10 Heteroaryl, -C(=O)OC 6-10 Aryl, -OC(=O)C 6-10 Aryl, -OC(=O)C 5- 10 Heteroaryl, -C(=O)OC 5-10 Heteroaryl, -OC(=O)C 3-8 Heterocycloalkyl, -C(=O)OC 3-8 Heterocycloalkyl, -OC(=O)C 3-8 Cycloalkyl, -C(=O)OC 3-8 Cycloalkyl, -NHC(=O)C 3-8 Heterocycloalkyl, -NHC(=O)C 6-10 Aryl, -NHC(=O)C 5-10 Heteroaryl, -NHC(=O)C 3-8 Cycloalkyl, -NHC(=O)C 3-8 Heterocycloalkyl, -NHC(=O)C 2-6 Alkenyl or -NHC(=O)C 2-6 substituted by a substituent of an alkynyl group, wherein the substituent C 1-6 Alkyl, C 1-6 Alkoxy, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, C 3-8 Heterocycloalkyl, C 6-10 Aryl, C 5-10 Heteroaryl, -NHC(=O)C 6-10 Aryl, -NHC(=O)C 5-10 Heteroaryl, -NHC(=O)C 3-8 Heterocycloalkyl or -NHC(=O)C 3-8 The cycloalkyl group is optionally further substituted by 1 to 3 groups selected from OH, F, Cl, Br, I, C 1-6 Alkyl, C 1-6 Alkoxy, -NR q4 R q5 Or substituted by a substituent of =O; R q1 Selected from C 1-6 Alkyl, C 1-6 Alkoxy or C6-10 Aryl; R q2 、R q3 Selected from H or C 1-6 Alkyl; wherein R q4 、R q5 Selected from H, C 1-6 Alkyl, -NH(C=NR q1 )NR q2 R q3 、-S(=O)2NR q2 R q3 、-C(=O)R q1 or -C(=O)NR q2 R q3 , wherein the C 1-6 The alkyl group is optionally further substituted by one or more groups selected from OH, F, Cl, Br, I, C 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, C 5-10 Heteroaryl, C 3-8 Cycloalkyl or C 3-8 is substituted by a substituent of a heterocycloalkyl group; or R q4 With R q5 and the N atom form a 3- to 8-membered heterocyclic ring, which may contain one or more heteroatoms selected from N, O or S.

[0207] Halogens include F, Cl, Br and I.

[0208] Halogens include F, Cl, Br and I.

[0209] "Pharmaceutically acceptable salt" or "pharmaceutically acceptable salt thereof" refers to a salt of the compound of the present invention that retains the biological effectiveness and properties of the free acid or free base, and the free acid is obtained by reacting with a non-toxic inorganic base or organic base, or the free base is obtained by reacting with a non-toxic inorganic acid or organic acid.

[0210] A "pharmaceutical composition" refers to a mixture of one or more compounds described herein, their pharmaceutically acceptable salts or prodrugs, and other chemical components, wherein "other chemical components" refers to pharmaceutically acceptable carriers, excipients, and / or one or more other therapeutic agents.

[0211] "Carrier" refers to a material that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound.

[0212] "Excipient" refers to an inert substance added to a pharmaceutical composition to facilitate administration of a compound. Non-limiting examples include calcium carbonate, calcium phosphate, sugars, starches, cellulose derivatives (including microcrystalline cellulose), gelatin, vegetable oils, polyethylene glycols, diluents, granulating agents, lubricants, binders, and disintegrants.

[0213] "Stereoisomers" refer to isomers resulting from different spatial arrangements of atoms in a molecule, including cis-trans isomers, enantiomers, and conformational isomers.

[0214] "Tautomers" or "tautomeric forms" refer to structural isomers of different energies that are interconvertible via a low energy barrier. For example, proton tautomers (also known as prototropic tautomers) include interconversions via proton migration, such as keto-enol isomerization, imine-enamine isomerization, lactam-lactim isomerization, and the like. The present disclosure includes tautomers of any of the described compounds.

[0215] "Pharmaceutically acceptable salt" or "pharmaceutically acceptable salt thereof" refers to a salt of the compound of the present invention that retains the biological effectiveness and properties of the free acid or free base, and the free acid is obtained by reacting with a non-toxic inorganic base or organic base, or the free base is obtained by reacting with a non-toxic inorganic acid or organic acid.

[0216] "Optional" or "optionally" or "selectively" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, "a heterocyclyl optionally substituted with an alkyl group" means that the alkyl group may but need not be present, and that the description includes instances where the heterocyclyl group is substituted with an alkyl group and instances where the heterocyclyl group is not substituted with an alkyl group. BRIEF DESCRIPTION OF THE DRAWINGS

[0217] FIG1 shows the curve of tumor volume changes in tumor-bearing mice in Example 1.

[0218] FIG2 shows the body weight change curve of tumor-bearing mice in Example 1.

[0219] FIG3 is a curve showing the change in tumor volume of the NCI-H1373 mouse tumor-bearing model in Example 2.

[0220] FIG4 is a curve showing the weight change rate of mice in the NCI-H1373 mouse tumor-bearing model in Example 2.

[0221] FIG5 is a curve showing the change in tumor volume of MDA-MB-231 subcutaneous humanized model mice in Example 3.

[0222] FIG6 is a curve showing the change in tumor volume of HCC827 subcutaneous humanized model mice in Example 4. DETAILED DESCRIPTION

[0223] The following examples illustrate the technical solutions of the present invention in detail, but the protection scope of the present invention includes but is not limited to them.

[0224] The compound of formula (I) or its specific structure according to the present invention can be prepared by the method of patent WO2022242750A1. Specifically, compound A used in the embodiment of the present invention is compound 1 in patent WO2022242750A1.

[0225] Example 1

[0226] Drug efficacy test in CT26 mouse tumor model

[0227] Mouse colorectal cancer cells CT26 were cultured in DMEM supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin. When the cells reached the exponential growth phase, they were harvested by trypsinization and counted. After inoculation, they were subcutaneously inoculated in the right flank of female BALB / c mice at a cell density of 1 × 10 6 / mouse, inoculation volume is 100μL. When the tumor grows to 30-80mm 3 Around 6:00 p.m., animals were randomly divided into three groups based on tumor size: a blank group, a compound A (250 mg / kg, BID) group, and a RBN-2397 (250 mg / kg, BID) group, with eight animals in each group. The test substance was prepared using DMSO + 30% HP-β-CD at a 5 / 95 (v / v) ratio and administered by gavage at a volume of 5 mL / kg for 17 days. During the dosing period, tumor volume and animal body weight were measured twice weekly, and tumor growth and body weight change curves were plotted, as shown in Figures 1 and 2.

[0228] The results showed that in the CT26 subcutaneous transplant tumor model, compound A had better in vivo anti-tumor effect than RBN-2397, especially for colorectal cancer, and exhibited good safety.

[0229] Example 2

[0230] Efficacy test in NCI-H1373 mouse tumor model

[0231] Human lung cancer cell line NCI-H1373 (Nanjing Kebai Biotechnology Co., Ltd., catalog number CBP60162) was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. When the cells reached the exponential growth phase, they were trypsinized, harvested, counted, resuspended in PBS, and inoculated subcutaneously in the right flank of female CB17 SCID mice at a cell density of 5 × 10 6The inoculation volume was 200 μL (100 μL NCI-H1373 cells + 100 μL Matrigel mixture). 3 Around 24 mice were enrolled and randomly assigned to three experimental groups of 8 mice each. The groups were blank, compound A (100 mg / kg, BID), and RBN-2397 (100 mg / kg, BID). Compound A and RBN-2397 were prepared using 0.5% MC and administered orally at a volume of 10 mL / kg. During the administration period, tumor volume was measured twice a week and a tumor growth curve was drawn. The mice were weighed twice a week to calculate the rate of change in animal weight, as shown in Figures 3 and 4.

[0232] The results showed that in the NCI-H1373 mouse tumor model, compound A (100 mg / kg, BID) was more effective than RBN-2397 (100 mg / kg, BID) in treating lung cancer.

[0233] Example 3

[0234] In vivo efficacy study of MDA-MB-231 subcutaneous humanized model

[0235] MDA-MB-231 cells (human breast cancer cells) were cultured in Leibovitz's L-15 medium supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin solution, and 0.01 mg / mL insulin. When the cells reached the exponential growth phase, they were trypsinized, harvested, counted, resuspended in DPBS, and inoculated subcutaneously on the right side of the back of female C-NKG mice at a seeding rate of 1 × 10 cells. 7 The inoculation volume was 200 μL. Frozen PBMCs were revived, resuspended in DPBS and inoculated into the tail vein of mice. The inoculation volume was 5×10 6 The inoculation volume is 200 μL. When the average tumor volume reaches 80-120 mm 3 At about 1:10 pm, 12 mice were selected based on tumor volume and mouse body weight and randomly assigned to two experimental groups, with 6 mice in each group. The groups were set up as blank group and compound A (125 mg / kg, BID) administration group. Compound A was prepared using DMSO + 30% HP-β-CD (5:95, v / v) and administered by gavage at a dosage of 10 mL / kg. During the administration period, the tumor volume was measured twice a week and the tumor growth curve was drawn. The mice were weighed twice a week to calculate the animal weight change rate. At the end of the experiment, the mouse tumors were removed, weighed and photographed. The tumor growth curve is shown in Figure 5.

[0236] Conclusion: Compound A has a good tumor inhibitory effect on human breast cancer cells in the MDA-MB-231 model.

[0237] Example 4

[0238] In vivo efficacy study of HCC827 subcutaneous humanized model

[0239] HCC827 cells (human non-small cell lung cancer cells) were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin solution, and 0.01 mg / mL insulin. When the cells reached the exponential growth phase, they were trypsinized, harvested, counted, resuspended in DPBS, and inoculated subcutaneously on the right side of the back of female B-NDG mice at a seeding rate of 1 × 10 cells. 7 The inoculation volume was 200 μL. Frozen PBMCs were revived, resuspended in DPBS and inoculated into the tail vein of mice. The inoculation volume was 1×10 7 The inoculation volume was 200 μL. When the average tumor volume reached about 80-120 mm3, 12 mice were selected according to the tumor volume and mouse body weight and randomly assigned to two experimental groups, with 6 mice in each group. The groups were set up as blank group and compound A (125 mg / kg, BID) administration group. Compound A was prepared using DMSO+30% HP-β-CD (5:95, v / v) and administered by gavage at a dosing volume of 10 mL / kg. During the administration period, the tumor volume was measured twice a week and the tumor growth curve was drawn, as shown in Figure 6.

[0240] Conclusion: Compound A has a good tumor inhibitory effect on human non-small cell lung cancer cells in the HCC827 model.

[0241] Example 5

[0242] In vivo efficacy of MC38.hVEGFA humanized transgenic mouse model

[0243] MC38.hVEGFA cells (mouse colon cancer cells) were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin solution, and 0.01 mg / mL insulin. When the cells reached the exponential growth phase, they were trypsinized, harvested, counted, resuspended in DPBS, and inoculated subcutaneously on the right side of the back of female B-hPD-1 / hPD-L1 / hVEGFA mice at a seeding density of 1×10 cells. 6The inoculation volume was 100 μL. When the average tumor volume reached about 60-120 mm3, 12 mice were selected according to the tumor volume and mouse body weight and randomly assigned to two experimental groups, with 6 mice in each group. The groups were set up as blank group and compound A (125 mg / kg, BID) administration group. Compound A was prepared using DMSO+30% HP-β-CD (5:95, v / v) and administered by gavage at a dosage volume of 10 mL / kg. During the administration period, the tumor volume was measured twice a week and the tumor growth curve was drawn.

[0244] Conclusion: Compound A has a good tumor inhibitory effect on colon cancer cells in the MC38.hVEGFA humanized transgenic mouse model.

[0245] Example 6

[0246] Clinical trial dosing regimen

[0247] Compound A dosage: 200 mg group: once before breakfast and dinner, 100 mg each time;

[0248] 400mg group: once before breakfast and dinner, 200mg each time;

[0249] 600mg group: once before breakfast and dinner, 300mg each time;

[0250] 800mg group: once before breakfast and dinner, 400mg each time;

[0251] 1000mg group: 500mg each time, once before breakfast and dinner.

[0252] Medication schedule: single-dose period: administer for 1 day and then stop for 2 days for observation; multiple-dose period: continuous medication for 21 days constitutes one treatment cycle.

[0253] The results showed that Compound A has a remarkable safety profile in clinical applications and is significantly effective in treating malignant solid tumors, particularly non-small cell lung cancer, head and neck cancer, and gynecological tumors (including cervical cancer, ovarian cancer, and endometrial cancer).

[0254] Example 7

[0255] Clinical evaluation

[0256] 1. Study objective: To evaluate the safety, tolerability, and preliminary efficacy of Compound A in patients with advanced solid tumors.

[0257] 2. Clinical subjects: Age range: 18 years (minimum) to no upper limit (maximum); Gender: male or female; Patients with advanced malignant solid tumors confirmed by histology or cytology, who have failed standard treatment, have no standard treatment options, or are not currently suitable for standard treatment. According to RECIST 1.1 criteria, at least one evaluable lesion must be present.

[0258] 3. Experimental plan:

[0259] Dosage and Administration: A dose escalation study of 100 mg BID, 200 mg BID, 300 mg BID, 400 mg BID, and 500 mg BID, including three phases: screening phase, treatment phase, and follow-up phase. The single-dose phase (C0) of the treatment phase and the first cycle (C1) of the multiple-dose phase are the DLT observation phase. During the single-dose phase (C0D1-C0D3), the drug is administered once on day 1, and the drug is stopped for observation for 2 days. If no DLT event occurs, the first cycle of the multiple-dose phase (C1D1-C1D21) is entered, with the drug administered twice daily for 21 consecutive days as one treatment cycle. Dosage schedule: Until the subject experiences disease progression, intolerable toxicity, death, or meets other termination criteria (whichever occurs first).

[0260] 4. End point indicators:

[0261] Table 1 Endpoint indicators

[0262] 5. Clinical efficacy evaluation results

[0263] 5.1 Clinical efficacy evaluation results for non-small cell lung cancer

[0264] Table 2 Evaluation of efficacy of subjects

[0265] 5.2 Clinical efficacy evaluation results for head and neck cancer

[0266] Table 3 Evaluation of efficacy of subjects

[0267] 5.3 Clinical efficacy evaluation results of gynecological tumors

[0268] Table 4 Evaluation of efficacy of subjects

[0269] Clinical study results have shown that tumor growth in patients with non-small cell lung cancer was significantly inhibited during the clinical trial period, with good treatment safety. In other indications for patients with advanced malignant solid tumors, tumor growth was also inhibited, and the safety and tolerability of the treatment were excellent. This was particularly true for patients with head and neck cancer and gynecological cancers (including cervical cancer, ovarian cancer, and endometrial cancer), where tumor growth was significantly inhibited, with excellent safety and tolerability.

[0270] The specification of the present invention describes the specific implementation scheme in detail. Those skilled in the art should recognize that the above implementation scheme is exemplary and cannot be understood as limiting the present invention. For those skilled in the art, without departing from the principles of the present invention, by making several improvements and modifications to the present invention, the technical solutions obtained by these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. Use of a PARP7 inhibitor in the preparation of a medicament for treating and / or preventing cancer or tumors.

2. PARP7 inhibitors for use as medicaments.

3. PARP7 inhibitors for use in the treatment and / or prevention of cancer or tumors.

4. A method for treating and / or preventing cancer or tumors, comprising administering a therapeutically or preventively effective amount of a PARP7 inhibitor to a subject in need thereof.

5. The method according to any one of claims 1 to 4, wherein the PARP7 inhibitor is selected from RBN-2397, ONO-7119, QLS1103, JAB-26766, NSP-5020, NSP-5033, EB400, or a compound represented by formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof: in: X1 is NH, O or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is O or a single bond; X3 and X4 are each independently C or N; R 1a 、R 1b Each independently is H, D or C 1-6 Alkyl; or R 1a 、R 1b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group; R 2a 、R 2b Each independently is H, D or C 1-6 Alkyl; or R 2a 、R 2b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group; R3 is H, D, C 1-6 Alkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 Alkyl; or R4, R5 and the connected carbon atom form a 3 to 5-membered cycloalkyl; R6 and R7 are each independently H, D or C 1-6 Alkyl; or R6, R7 and the connected carbon atom form C=O; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the carbon atom to which they are connected form C=O; or R8 and R9 and the carbon atom to which they are connected form a 3- to 5-membered cycloalkyl; R 10 Each independently is C 1-6 Alkyl, C 1-6 Alkoxy, CONR 10a R 10b , halogen, cyano, S(O)2R 10c SR 10d or a 3 to 5-membered cycloalkyl group, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10a 、R 10b 、R 10c 、R 10d Each independently is H, D or C 1-6 alkyl; A is R a C 1-6 Alkyl, C 3-5 Cycloalkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; B is a 5- to 10-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms; m is 1, 2, or 3; n is 0, 1, 2, or 3; p is 0, 1, 2 or 3.

6. The use according to claim 5, wherein: X1 is NH, O or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is O or a single bond; X3 and X4 are each independently C or N; R 1a 、R 1b Each independently is H, D or C 1-6 alkyl; R 2a 、R 2b Each independently is H, D or C 1-6 Alkyl; or R 2a 、R 2b Together with the carbon atom to which it is attached, it forms a 3- to 5-membered cycloalkyl group; R3 is H, D, C 1-6 Alkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 Alkyl; or R4, R5 and the connected carbon atom form a 3 to 5-membered cycloalkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O; R 10 Each independently is C 1-6 Alkyl, C 1-6 Alkoxy, CONR 10a R 10b , halogen, cyano, S(O)2R 10c SR 10d or a 3 to 5-membered cycloalkyl group, the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10a 、R 10b 、R 10c 、R 10d Each independently is H, D or C 1-6 alkyl; A is R a C 1-6 Alkyl, C 3-5 Cycloalkyl, halogen or cyano, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms; m is 1, 2, or 3; n is 0, 1, 2, or 3: p is 0, 1, 2 or 3.

7. The use according to claim 5, wherein the compound represented by formula (I) has the structure of formula (I-1): in X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is 0; X3 and X4 are each independently C or N; R 1a 、R 1b Each independently is H, D or C 1-6 alkyl; R 2a 、R 2b Each independently is H, D or C 1-6 alkyl; R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 alkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8 and R9 form C=O with the carbon atom to which they are connected; R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; C is a 5- to 6-membered heterocyclic ring containing 1 to 3 N heteroatoms; m is 1, 2, or 3; n is 0, 1, 2 or 3.

8. The use according to claim 5, wherein the compound represented by formula (I) has the structure of formula (I-2): in: X1 is NH; X2 is 0; R 1a 、R 1b Each independently is H, D or C 1-6 alkyl; R 2a 、R 2b Each independently is H, D or C 1-6 alkyl; R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 alkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8 and R9 and the carbon atom to which they are attached form C=O; R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; m is 1, 2, or 3; n is 0, 1, 2 or 3.

9. The use according to claim 8, wherein: X1 is NH; X2 is 0; R 1a 、R 1b Each independently is H, D or C 1-6 alkyl; R 2a 、R 2b Each independently is H, D or C 1-6 alkyl; R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H, D or C 1-6 alkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl, or R8 and R9 form C=O with the carbon atom to which they are connected; R 10 C 1-6 Alkyl, cyano, or SR 10d , the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; m is 1, 2, or 3; n is 0, 1, 2 or 3.

10. The use according to claim 9, wherein: X1 is selected from NH; X2 is selected from O; R 1a 、R 1b Each independently selected from H, D or C 1-6 alkyl; R 2a 、R 2b Each independently selected from H, D or C 1-6 alkyl; R3 is H, D, C 1-6 Alkyl or halogen, the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R4 and R5 are each independently H or D; R6 and R7 are each independently H or D; R8 and R9 are each independently H or D; R 10 CF3 or SR 10d ; R 10d H, D or C 1-6 alkyl; A is B is m is 1, 2, or 3; n is 0, 1, 2 or 3.

11. The use according to claim 10, wherein: X1 is selected from NH; X2 is selected from O; R 1a 、R 1b Each independently selected from H, D or C 1-3 alkyl; R 2a 、R 2b Each independently selected from H, D or C 1-3 alkyl; R3 is selected from H, D or CF3; R4 and R5 are each independently selected from H or D; R6 and R7 are each independently selected from H or D; R8 and R9 are each independently selected from H or D; R 10 is CF3; A is B is m is 1, 2, or 3; n is 0, 1 or 2.

12. The use according to claim 5, wherein the compound represented by formula (I) has the structure of formula (I-3): in: X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is 0; R 1a 、R 1b Each independently is H, D or C 1-6 alkyl; R 2a 、R 2b Each independently is H, D or C 1-6 alkyl; R4 and R5 are each independently H, D or C 1-6 alkyl; R6 and R7 are each independently H, D or C 1-6 alkyl; R8 and R9 are each independently H, D or C 1-6 Alkyl; or R8, R9 and the connected carbon atom form C=O; R 10 C 1-6 Alkyl, C 1-6 Alkoxy, cyano or SR 10d , the C 1-6 Alkyl, C 1-6 Alkoxy is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is a 5- to 6-membered carbocyclic or heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S; m is 1, 2, or 3; n is 0, 1, 2 or 3.

13. The use according to claim 12, wherein: X1 is NH or a 4- to 6-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N and O; X2 is 0; R 1a 、R 1b Each independently is H, D or C 1-3 alkyl; R 2a 、R 2b Each independently is H, D or C 1-3 alkyl; R4 and R5 are each independently H, D or C 1-3 alkyl; R6 and R7 are each independently H, D or C 1-3 alkyl; R8 and R9 are each independently H, D or C 1-3 Alkyl; or R8 and R9 form C=O with the carbon atom to which they are connected; R 10 C 1-6 Alkyl, cyano or SR 10d , the C 1-6 The alkyl group is optionally substituted with 1 to 3 halogens; R 10d H, D or C 1-6 alkyl; A is B is m is 1, 2, or 3; n is 0, 1 or 2.

14. The use according to claim 13, wherein: X1 is NH; X2 is 0; R 1a 、R 1b Each independently is H, D or C 1-3 alkyl; R 2a 、R 2b Each independently is H or D; R4 and R5 are each independently H or D; R6 and R7 are each independently H or D; R8 and R9 are each independently H or D; R 10 is CF3; A is B is m is 1, 2, or 3: n is 0, 1 or 2.

15. The use according to any one of claims 1 to 14, wherein the PARP7 inhibitor is the following compound:

16. The use according to any one of claims 1 to 15, wherein the PARP7 inhibitor is contained in a pharmaceutical composition further comprising one or more pharmaceutically acceptable excipients, diluents or carriers.

17. Use according to any one of claims 1 to 16, wherein the tumor is selected from solid tumors and / or hematological tumors.

18. The use according to any one of claims 1 to 17, wherein the tumor is selected from malignant solid tumors; preferably, the tumor is selected from advanced malignant solid tumors.

19. The method of claim 17, wherein the solid tumor is selected from colorectal cancer, breast cancer, central nervous system cancer, uterine cancer, cervical cancer, kidney cancer, adrenal cancer, lung cancer, esophageal cancer, head and neck cancer, ovarian cancer, pancreatic cancer, liver cancer, prostate cancer, endometrial cancer, testicular cancer, gastric cancer, laryngeal cancer, urinary tract cancer, bladder cancer, colon cancer, rectal cancer, thyroid cancer, bone cancer, epithelial cancer, bile duct cancer, gallbladder cancer, skin cancer, mesothelioma, basal cell carcinoma, adenoid cystic carcinoma, leiomyosarcoma, gastrointestinal stromal tumor, Ewing sarcoma, Kaposi sarcoma, or a PARP7-amplified advanced solid tumor: The blood tumor is selected from leukemia, myeloma and lymphoma; preferably, the blood tumor is selected from Hodgkin's lymphoma or non-Hodgkin's lymphoma, multiple myeloma, B-cell lymphoma, small lymphocytic lymphoma, T-cell lymphoma, hairy cell lymphoma, Burkett's lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia.

20. The use according to claim 19, wherein the lung cancer is non-small cell lung cancer or neuroendocrine lung cancer; more preferably, the non-small cell lung cancer is lung squamous cell carcinoma or lung adenocarcinoma; preferably, the breast cancer is selected from hormone receptor-positive (HR+) breast cancer; preferably, the head and neck cancer is selected from head and neck squamous cell carcinoma; preferably, the uterine cancer is selected from endometrial cancer.

21. The use according to any one of claims 1 to 20, wherein the daily dose of the PARP7 inhibitor is 50 to 2000 mg / day, preferably 100 to 1500 mg / day, more preferably 200 to 1000 mg / day.

22. The use according to any one of claims 1 to 21, wherein the PARP7 inhibitor is administered three times a day, twice a day, once a day, once every two days, once every three days, once every four days, once every five days, once every six days, once a week, once every two weeks, once every three weeks, or once every four weeks; preferably, twice a day or once a day.

23. The use according to any one of claims 1 to 22, wherein the daily dose of the PARP7 inhibitor is 25-100 mg BID, preferably 50-750 mg BID, more preferably 100-500 mg BID.

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