Polycyclic compound

Abstract

Provided herein are compounds of formula (I), or pharma- ceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds described herein (including pharma- ceutically acceptable salts of the compounds described herein), and methods of synthesizing the same.Also provided herein are methods of treating diseases and / or conditions with the compounds of formula (I), or pharma- ceutically acceptable salts thereof.

Description

[Technical field]

[0001] Incorporation by reference of any priority application For example, any and all applications in which a foreign or domestic priority claim is identified in an Application Data Sheet or Request filed with this application are incorporated by reference herein under 37 CFR §1.57 and Rules 4.18 and 20.6, including U.S. Provisional Application No. 63 / 269,329, filed March 14, 2022, and U.S. Provisional Application No. 63 / 363,144, filed April 18, 2022, each of which is incorporated by reference in their entirety.

[0002] This application relates to the fields of chemistry, biochemistry, and medicine. Disclosed herein are compounds of formula (I), or pharma- ceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds described herein (including pharma- ceutically acceptable salts of the compounds described herein), and methods of synthesizing them. Also disclosed herein are methods of treating diseases and / or conditions with compounds of formula (I), or pharma- ceutically acceptable salts thereof. [Background technology]

[0003] According to the National Cancer Institute, an estimated 1,806,590 new cases of cancer will be diagnosed in the United States in 2020, and 606,520 people will die from the disease. The most common cancers are breast, lung and bronchial, prostate, colon and rectal, melanoma of the skin, bladder, non-Hodgkin's lymphoma, kidney and renal pelvis, endometrial, leukemia, pancreatic, thyroid, and liver cancer. Summary of the Invention

[0004] Some embodiments disclosed herein relate to a compound of formula (I), or a pharma- ceutically acceptable salt thereof.

[0005] Some embodiments disclosed herein relate to pharmaceutical compositions that can include an effective amount of a compound of formula (I), or a pharma- ceutically acceptable salt thereof.

[0006] Some embodiments described herein relate to methods of treating a cancer described herein, which may include administering an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) to a subject having a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) in the manufacture of a medicament for treating a cancer described herein. Still other embodiments described herein relate to a pharmaceutical composition comprising an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) to treat a cancer described herein.

[0007] Some embodiments described herein relate to methods for inhibiting the growth of a malignant growth or tumor, which may include contacting the growth or tumor with an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), wherein the malignant growth or tumor results from a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), in the manufacture of a medicament for inhibiting the growth of a malignant growth or tumor, wherein the malignant growth or tumor results from a cancer described herein. Yet other embodiments described herein relate to an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), for inhibiting malignant growth or tumor growth, wherein the malignant growth or tumor results from a cancer described herein.

[0008] Some embodiments described herein relate to methods for treating a cancer described herein, which may include contacting a malignant growth or tumor with an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) in a subject having a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) in the manufacture of a medicament for treating a cancer described herein, which may include contacting a malignant growth or tumor resulting from a cancer described herein. Yet other embodiments described herein relate to an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), for treating a cancer described herein, which may include contacting a malignant growth or tumor resulting from a cancer described herein.

[0009] Some embodiments described herein relate to a method for inhibiting the activity of PARP1 in a cell, which may include providing an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) to a cancer cell derived from a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) in the manufacture of a medicament for inhibiting the activity of PARP1. Still other embodiments described herein relate to a pharmaceutical composition comprising an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) to inhibit the activity of PARP1.

[0010] Some embodiments described herein relate to methods for treating cancers described herein, which may include inhibiting the activity of PARP1 using an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof). Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), in the manufacture of a medicament for treating a cancer described herein by inhibiting the activity of PARP1. Still other embodiments described herein relate to a pharmaceutical composition comprising an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), to treat a cancer described herein by inhibiting the activity of PARP1.

[0011] These are other embodiments described in more detail below. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Accumulation of DNA damage without repair over a period of time can lead to the development of cancer. Poly(ADP-ribose) polymerase (PARP1 / 2) is an enzyme that senses DNA damage and adds branched PAR chains to facilitate DNA repair. PARP inhibitors are a class of small molecules that inhibit both PARP1 and PARP2 and have been approved as cancer drugs for tumors with BRCA1 / 2 mutations.

[0013] PARP1 is considered the primary target for PARP inhibitors, but currently approved PARP inhibitors also inhibit PARP2 and PARP3. Beyond its role in DNA repair, PARP1 has additional biological roles, including regulating the transcription of several genes involved in several cancers. Inhibition of PARP1 with PARP1-selective small molecules could potentially overcome some of the major toxicities observed with current PARP1 / 2 inhibitors and provide meaningful benefit to cancer patients.

[0014] Poly(ADP-ribose) polymerase (PARP)1 / 2 inhibitors selectively kill cancer cells that have defects in the homologous recombination repair pathway and have been approved for use in ovarian cancer, metastatic breast cancer, and prostate cancer. Clinical studies have shown that PARP1 / 2 inhibitors have antitumor activity in tumors with BRCA1 / 2 mutations, but cancer patients with alterations in the DNA damage repair pathway may benefit from PARP inhibitors. Mutations in the DNA damage repair pathway are observed in a wide range of tumor types, suggesting that PARP1 / 2 inhibitors may potentially have antitumor activity in some cancer types.

[0015] Although PARP inhibitors have demonstrated antitumor activity, adverse events observed in patients treated with PARP1 / 2 inhibitors have necessitated dose reduction and discontinuation of PARP1 / 2 inhibitors. Because the adverse events of PARP1 / 2 inhibitors are believed to result from inhibition of PARP2, small molecules that are potent and selective for PARP1 could retain antitumor activity and potentially minimize the adverse events observed with current PARP1 / 2 inhibitors.

[0016] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art.All patents, applications, published applications, and other publications referenced herein are incorporated by reference in their entirety unless otherwise stated.In the event that there are multiple definitions for a term in this specification, the definition in this section shall prevail unless otherwise stated.

[0017] When a group is described as "optionally substituted," the group can be unsubstituted or substituted with one or more of the indicated substituents. Similarly, when a group is described as "unsubstituted or substituted," if substituted, the substituent(s) can be selected from one or more of the indicated substituents. When no substituents are indicated, this means that the indicated "optionally substituted" or "substituted" group can be substituted with one or more groups (e.g., 1, 2, or 3) individually and independently selected from deuterium, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), heterocyclyl(alkyl), hydroxy, alkoxy, acyl, cyano, halogen, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, C-amido(alkyl), isocyanato, thiocyanato, nitro, azido, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, amino, monosubstituted amine, and disubstituted amine.

[0018] As used herein, "C" refers to a set of integers where "a" and "b" are integers. a -C b" refers to the number of carbon atoms in an alkyl, alkenyl, or alkynyl group, or the number of carbon atoms in a cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl group ring. That is, an alkyl, alkenyl, alkynyl, cycloalkyl ring, cycloalkenyl ring, aryl ring, heteroaryl ring, or heterocyclyl ring can contain from "a" to "b" carbon atoms, inclusive. Thus, for example, a "C1-C4 alkyl" group refers to all alkyl groups having 1 to 4 carbons, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-. When "a" and "b" are not specified for an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl group, the broadest range described in these definitions is assumed.

[0019] As used herein, "alkyl" refers to a straight or branched hydrocarbon chain that includes a fully saturated (no double or triple bonds) hydrocarbon group. The alkyl group may have 1 to 20 carbon atoms (each occurrence herein, a numerical range such as "1 to 20" refers to each integer within the given range, e.g., "1 to 20 carbon atoms" means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., including up to 20 carbon atoms, but this definition also encompasses occurrences of the term "alkyl" where no numerical range is specified). The alkyl group may also be a lower alkyl having 1 to 10 carbon atoms. The alkyl group may also be a lower alkyl having 1 to 6 carbon atoms. The alkyl group of the compound may be represented as "C1-C4 alkyl" or a similar designation. By way of example only, "C1-C4 alkyl" indicates that there are 1 to 4 carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, and hexyl. Alkyl groups can be substituted or unsubstituted.

[0020] As used herein, "alkenyl" refers to an alkyl group that contains one or more double bonds in a straight or branched hydrocarbon chain. The length of the alkenyl can vary. For example, an alkenyl can be any alkyl group, including C 2-4 Alkenyl, C 2-6 Alkenyl, or C 2-8 It may be an alkenyl. Examples of alkenyl groups include allenyl, vinylmethyl, and ethenyl. The alkenyl group may be unsubstituted or substituted.

[0021] As used herein, "alkynyl" refers to an alkyl group that contains one or more triple bonds in the straight or branched hydrocarbon chain. The length of the alkynyl can vary. For example, an alkynyl can be any of the C 2-4 Alkynyl, C 2-6Alkynyl, or C 2-8 It may be alkynyl. Examples of alkynyl include ethynyl and propynyl. Alkynyl groups may be unsubstituted or substituted.

[0022] As used herein, "cycloalkyl" refers to a monocyclic or polycyclic hydrocarbon ring system that is fully saturated (no double or triple bonds). When composed of more than one ring, the rings may be fused or linked together in a spiro fashion. Cycloalkyl groups may contain 3 to 10 atoms in the ring(s); 3 to 8 atoms in the ring(s), or 3 to 6 atoms in the ring(s). Cycloalkyl groups may be unsubstituted or substituted. Exemplary cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0023] As used herein, "cycloalkenyl" refers to a monocyclic or polycyclic hydrocarbon ring system containing one or more double bonds in at least one ring, but if more than one double bond is present, it is not possible to form a completely delocalized pi-electron system across all rings (otherwise the group is an "aryl" as defined herein). When composed of more than one ring, the rings may be fused or linked together in a spiro fashion. Cycloalkenyls may contain 3 to 10 atoms in the ring(s), or 3 to 8 atoms in the ring(s). Cycloalkenyl groups may be unsubstituted or substituted.

[0024] As used herein, "aryl" refers to a carbocyclic (all carbon) monocyclic or polycyclic aromatic ring system (including fused ring systems in which two carbon rings share a chemical bond) having a completely delocalized pi-electron system throughout all rings. The number of carbon atoms in an aryl group can vary. For example, an aryl group can be any of C6-C 14 Aryl groups, C6-C 10 It may be an aryl group or a C6 aryl group. Examples of aryl groups include, but are not limited to, benzene, naphthalene, and azulene. The aryl group may be substituted or unsubstituted.

[0025] As used herein, "heteroaryl" refers to monocyclic, bicyclic, and tricyclic aromatic ring systems (ring systems with a fully delocalized π-electron system) containing one or more heteroatoms (e.g., 1-5 heteroatoms), i.e., elements other than carbon, including but not limited to nitrogen, oxygen, and sulfur. The number of atoms in the ring(s) of a heteroaryl group can vary. For example, a heteroaryl group can contain 4-14 atoms in the ring(s), 5-10 atoms in the ring(s), or 5-6 atoms in the ring(s). Furthermore, the term "heteroaryl" includes fused ring systems in which two rings share at least one chemical bond, such as at least one aryl ring and at least one heteroaryl ring, or at least two heteroaryl rings. Examples of heteroaryl rings include, but are not limited to, furan, furazan, thiophene, benzothiophene, phthalazine, pyrrole, oxazole, benzoxazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, thiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, benzothiazole, imidazole, benzimidazole, indole, indazole, pyrazole, benzopyrazole, isoxazole, benzoisoxazole, isothiazole, triazole, benzotriazole, thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, purine, pteridine, quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline, and triazine. Heteroaryl groups can be substituted or unsubstituted.

[0026] As used herein, "heterocyclyl" refers to monocyclic, bicyclic, and tricyclic ring systems in which carbon atoms together with one to five heteroatoms constitute the ring system. However, the heterocycle may optionally contain one or more unsaturated bonds positioned in such a way that a completely delocalized pi-electron system does not occur throughout the entire ring. The number of atoms in the ring(s) of a heterocyclyl group may vary. For example, a heterocyclyl group may contain 4 to 14 atoms in the ring(s), 5 to 10 atoms in the ring(s), or 5 to 6 atoms in the ring(s). The heteroatom(s) are elements other than carbon, including, but not limited to, oxygen, sulfur, and nitrogen. The heterocycle may further contain one or more carbonyl or thiocarbonyl functional groups, and as defined, includes oxo and thio systems such as lactams, lactones, cyclic imides, cyclic thioimides, and cyclic carbamates. When composed of two or more rings, the rings may be linked together in a fused fashion. Additionally, any nitrogen of a heterocyclyl may be quaternized. A heterocyclyl group may be unsubstituted or substituted.Examples of such "heterocyclyl groups" include 1,3-dioxine, 1,3-dioxane, 1,4-dioxane, 1,2-dioxolane, 1,3-dioxolane, 1,4-dioxolane, 1,3-oxathiane, 1,4-oxathiine, 1,3-oxathiolane, 1,3-dithiole, 1,3-dithiolane, 1,4-oxathiane, tetrahydro-1,4-thiazine, 2H-1,2-oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, trioxane, hexahydro-1,3,5-triazine, imidazoline, imidazolidine, isoxyl aryl, aryl ... These include, but are not limited to, sazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidine, morpholine, oxirane, piperidine N-oxide, piperidine, piperazine, pyrrolidine, pyrrolidone, pyrrolidione, 4-piperidone, pyrazoline, pyrazolidine, 2-oxopyrrolidine, tetrahydropyran, 4H-pyran, tetrahydrothiopyran, thiamorpholine, thiamorpholine sulfoxide, thiamorpholine sulfone, and their benzo-fused analogs (e.g., benzimidazolidinone, tetrahydroquinoline, and 3,4-methylenedioxyphenyl).

[0027] As used herein, "cycloalkyl(alkyl)" refers to a cycloalkyl group linked as a substituent through a lower alkylene group. The lower alkylene and aryl groups of cycloalkyl(alkyl) can be substituted or unsubstituted. Examples include, but are not limited to, cyclopropyl-CH-, cyclobutyl-CH-, cyclopentyl-CH-, cyclohexyl-CH-, cyclopropyl-CHCH-, cyclobutyl-CHCH-, cyclopentyl-CHCH-, cyclohexyl-CHCH-, cyclopropyl-CHCHCH-, cyclobutyl-CHCHCH-, cyclopentyl-CHCHCH-, cyclohexyl-CHCHCH-, cyclopropyl-CHCHCH-, cyclobutyl-CHCHCH-, cyclopentyl-CHCHCH-, cyclohexyl-CHCHCH-, cyclopropyl-CHCHCHCH-, cyclobutyl-CHCHCH-, cyclopentyl-CHCHCH-, cyclohexyl-CHCHCH-, cyclopropyl-CHCHCHCH-, cyclobutyl-CHCHCHCH-, cyclopentyl-CHCHCHCH-, and cyclohexyl-CHCHCHCH-.

[0028] As used herein, "aryl(alkyl)" refers to an aryl group linked as a substituent through a lower alkylene group. The lower alkylene and aryl groups of the aryl(alkyl) can be substituted or unsubstituted. Examples include, but are not limited to, benzyl, 2-phenyl(alkyl), 3-phenyl(alkyl), and naphthyl(alkyl).

[0029] As used herein, "heteroaryl(alkyl)" refers to a heteroaryl group linked as a substituent via a lower alkylene group. The lower alkylene and heteroaryl groups of heteroaryl(alkyl) can be substituted or unsubstituted. Examples include, but are not limited to, 2-thienyl(alkyl), 3-thienyl(alkyl), furyl(alkyl), thienyl(alkyl), pyrrolyl(alkyl), pyridyl(alkyl), isoxazolyl(alkyl), imidazolyl(alkyl), and their benzo-fused analogs.

[0030] "Heterocyclyl(alkyl)" refers to a heterocyclic group linked as a substituent via a lower alkylene group. The lower alkylene and heterocyclyl of heteroalicyclyl(alkyl) can be substituted or unsubstituted. Examples include, but are not limited to, tetrahydro-2H-pyran-4-yl(methyl), piperidin-4-yl(ethyl), piperidin-4-yl(propyl), tetrahydro-2H-thiopyran-4-yl(methyl), and 1,3-thiazinane-4-yl(methyl).

[0031] A "lower alkylene group" is a straight-chain -CH2- tethering group that forms bonds that link molecular fragments through their terminal carbon atoms. Examples include, but are not limited to, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), and butylene (-CH2CH2CH2CH2-). A lower alkylene group can be substituted by replacing one or more hydrogens of the lower alkylene group with the substituent(s) listed under the definition of "substituted." Additionally, when a lower alkylene group is substituted, the lower alkylene can be substituted by replacing both hydrogens on the same carbon with a cycloalkyl group (e.g., [ka] )

[0032] As used herein, "alkoxy" refers to the formula -OR, where R is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl), as defined herein. A non-limiting list of alkoxy is methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, phenoxy, and benzyloxy. In some cases, alkoxy can be -OR, where R is an unsubstituted C 1-4Alkyl. Alkoxy can be substituted or unsubstituted.

[0033] As used herein, "acyl" refers to hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl) linked as a substituent through a carbonyl group. Examples include formyl, acetyl, propanoyl, benzoyl, and acryl. Acyl can be substituted or unsubstituted.

[0034] As used herein, "hydroxyalkyl" refers to an alkyl group in which one or more hydrogen atoms are replaced by a hydroxy group. Exemplary hydroxyalkyl groups include, but are not limited to, 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, and 2,2-dihydroxyethyl. Hydroxyalkyl can be substituted or unsubstituted.

[0035] As used herein, "haloalkyl" refers to an alkyl group in which one or more of the hydrogen atoms are replaced by halogen (e.g., mono-haloalkyl, di-haloalkyl, and tri-haloalkyl). Such groups include, but are not limited to, chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-chloro-2-fluoromethyl, and 2-fluoroisobutyl. Haloalkyl can be substituted or unsubstituted.

[0036] As used herein, "haloalkoxy" refers to O-alkyl groups and O-monocyclic cycloalkyl groups in which one or more of the hydrogen atoms are replaced by halogen (e.g., mono-haloalkoxy, di-haloalkoxy, and tri-haloalkoxy). Such groups include, but are not limited to, chloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1-chloro-2-fluoromethoxy, 2-fluoroisobutoxy, chloro-substituted cyclopropyl, fluoro-substituted cyclopropyl, chloro-substituted cyclobutyl, and fluoro-substituted cyclobutyl. In some cases, a haloalkoxy can be -OR, where R is a C substituted with 1, 2, or 3 halogens. 1-4 Alkyl. Haloalkoxy can be substituted or unsubstituted.

[0037] A "sulfenyl" group refers to the "-SR" group, where R can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). The sulfenyl can be substituted or unsubstituted.

[0038] A "sulfinyl" group refers to a "-S(=O)-R" group, where R can be the same as defined for sulfenyl. Sulfinyl can be substituted or unsubstituted.

[0039] A "sulfonyl" group refers to a "SO2R" group, where R can be the same as defined for sulfenyl. The sulfonyl can be substituted or unsubstituted.

[0040] An "O-carboxy" group refers to an "RC(=O)O-" group, where R can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl), as defined herein. O-carboxy can be substituted or unsubstituted.

[0041] The terms "ester" and "C-carboxy" refer to the group "-C(=O)OR" where R can be the same as defined for O-carboxy. Esters and C-carboxy can be substituted or unsubstituted.

[0042] A "thiocarbonyl" group refers to a "-C(=S)R" group, where R can be the same as defined for O-carboxy. Thiocarbonyl can be substituted or unsubstituted.

[0043] A "trihalomethanesulfonyl" group refers to an "X3CSO2-" group where each X is a halogen.

[0044] The "trihalomethanesulfonamide" group is "X3CS(O)2N(R A )-" group, each X is a halogen, and R A is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl).

[0045] The term "amino," as used herein, refers to the group --NH.

[0046] As used herein, the term "hydroxy" refers to an --OH group.

[0047] A "cyano" group refers to a "-CN" group.

[0048] The term "azido," as used herein, refers to the --N3 group.

[0049] An "isocyanato" group refers to a "-NCO" group.

[0050] A "thiocyanato" group refers to a "-CNS" group.

[0051] An "isothiocyanato" group refers to a "-NCS" group.

[0052] A "mercapto" group refers to a "-SH" group.

[0053] A "carbonyl" group refers to a -C(=O)- group.

[0054] An "S-sulfonamide" group is R A and R B may be independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A R B )" group. S-sulfonamides can be substituted or unsubstituted.

[0055] An "N-sulfonamide" group is one selected from R and R A RSO2N(R) may be independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A )-" group. N-Sulfonamides can be substituted or unsubstituted.

[0056] The "O-carbamyl" group is R A and R B are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl); A R B )" group. O-Carbamyl can be substituted or unsubstituted.

[0057] An "N-carbamyl" group is R and R AROC(═O)N(R) may be independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A N-carbamyl refers to a "—" group. N-carbamyl can be substituted or unsubstituted.

[0058] The "O-thiocarbamyl" group is R A and R B are independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl); A R B )" group. O-thiocarbamyl can be substituted or unsubstituted.

[0059] An "N-thiocarbamyl" group is R and R A ROC(=S)N(R) may be independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A N-thiocarbamyl refers to a "thiocarbamyl" group. N-thiocarbamyl can be substituted or unsubstituted.

[0060] A "C-amide" group is R A and R B may be independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A R B ) group. C-amides can be substituted or unsubstituted.

[0061] An "N-amido" group is one in which R and R Amay be independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A N-amides refer to an "N-amide" group. N-amides can be substituted or unsubstituted.

[0062] "Monosubstituted amine" is R A may be independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A ". Monosubstituted amines can be substituted or unsubstituted. In some cases, monosubstituted amines are represented by the formula -NHR A R A is unsubstituted C 1-6 It can be alkyl or unsubstituted or substituted benzyl.

[0063] "Disubstituted amine" is R A and R B may be independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl). A R B ". Monosubstituted amines can be substituted or unsubstituted. In some cases, monosubstituted amines are represented by -NR A R B R A and R B are independently unsubstituted C 1-6 It can be alkyl or unsubstituted or substituted benzyl.

[0064] A "ketoamide" group is R A and R Bmay be independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, aryl(alkyl), heteroaryl(alkyl), or heterocyclyl(alkyl); A R B ) group. Ketoamides can be substituted or unsubstituted.

[0065] The term "halogen atom" or "halogen" as used herein means any one of the radioactive stable atoms in column 7 of the periodic table of the elements, such as fluorine, chlorine, bromine, and iodine.

[0066] Where the number of substituents is not specified (e.g., haloalkyl), one or more substituents may be present. For example, "haloalkyl" may include one or more of the same or different halogens. As another example, "C1-C3 alkoxyphenyl" may include one or more of the same or different alkoxy groups containing 1, 2, or 3 atoms.

[0067] As used herein, abbreviations for any protecting groups, amino acids, and other compounds are in accordance with their common usage, recognized abbreviations, or the IUPAC-IUB Commission on Biochemical Nomenclature (see Biochem. 11:942-944 (1972)), unless otherwise indicated.

[0068] The term "pharmaceutical acceptable salt" refers to a salt of a compound that does not cause significant irritation to an organism to which it is administered and does not abolish the biological activity and properties of the compound. In some embodiments, the salt is an acid addition salt of the compound. Pharmaceutical salts can be obtained by reacting the compound with inorganic acids, hydrohalic acids (e.g., hydrochloric acid or hydrobromic acid), sulfuric acid, nitric acid, phosphoric acid, and the like. Pharmaceutical salts can also be obtained by reacting the compound with organic acids, such as aliphatic or aromatic carboxylic or sulfonic acids, for example, formic acid, acetic acid, succinic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, nicotinic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, or naphthalenesulfonic acid. Pharmaceutical salts can also be obtained by reacting the compounds with bases to form ammonium salts, alkali metal salts (e.g., sodium or potassium salts), alkaline earth metal salts (e.g., calcium or magnesium salts), salts of organic bases (e.g., dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, C1-C7 alkylamines, cyclohexylamine, triethanolamine, ethylenediamine), and salts with amino acids (e.g., arginine and lysine), etc.

[0069] Terms and phrases used in this application, and variations thereof, particularly in the appended claims, unless expressly stated otherwise, should be construed as open ended rather than limiting. As an example of the foregoing, the term "including" should be read to mean "including, but not limited to," and the term "comprising" as used herein is synonymous with "including," "containing," or "characterized by," and is inclusive or open ended and does not exclude additional, unrecited elements or method steps. The term "having" should be interpreted as "having at least." The term "includes" should be interpreted as "including, but not limited to." The term "examples" is used to provide illustrative examples of an item of discussion, rather than an exhaustive or exclusive enumeration thereof. In addition, the term "comprising" should be interpreted synonymously with the phrases "having at least" or "including at least." When used in the context of a compound or composition, the term "comprising" means that the compound or composition includes at least the recited features or components, but may include additional features or components.

[0070] With respect to the use of substantially any plural and / or singular term herein, one of ordinary skill in the art can convert from the plural to the singular and / or from the singular to the plural as appropriate to the context and / or application. The various singular / plural permutations may be expressly indicated herein for clarity. The indefinite article "a" or "an" does not exclude a plurality.

[0071] In any compound described herein having one or more chiral centers, unless the absolute configuration is explicitly indicated, it is understood that each center may be independently in the (R) or (S) configuration, or a mixture thereof. Thus, the compounds provided herein may be enantiomerically pure, enantiomerically enriched, racemic, diastereomerically pure, diastereomerically enriched, or a stereoisomeric mixture. In addition, in any compound described herein having one or more double bonds that generate geometric isomers that may be defined as E or Z, it is understood that each double bond may be independently E or Z, or a mixture thereof. Similarly, it is understood that all tautomeric forms are intended to be included in any compound described.

[0072] It is understood that if the compounds disclosed herein have unsatisfied valences, the valences should be filled with hydrogen or its isotopes, such as hydrogen-1 (protium) and hydrogen-2 (deuterium).

[0073] It is understood that the compounds described herein may be isotopically labeled. Substitution with an isotope such as deuterium may provide certain therapeutic advantages resulting from greater metabolic stability, such as increased in vivo half-life or reduced dosage requirements. Each chemical element depicted in a compound structure may include any isotope of that element. For example, in a compound structure, a hydrogen atom may be expressly disclosed or understood as being present in the compound. At any position of a compound where a hydrogen atom may be present, the hydrogen atom may be any isotope of hydrogen, including but not limited to hydrogen-1 (protium) and hydrogen-2 (deuterium). Thus, reference to a compound herein encompasses all possible isotopic forms, unless the context expressly indicates otherwise.

[0074] Where a range of values ​​is provided, it is to be understood that the upper and lower limits, as well as each intervening value between the upper and lower limits of the range, are encompassed within an embodiment.

[0075] compound Some embodiments disclosed herein relate to a compound of formula (I), or a pharma- ceutically acceptable salt thereof: [ka] In the formula, Y 1 is O (oxygen), CH2, or CR Y1 R Y2 R Y1 and R Y2 are independently deuterium, halogen, or unsubstituted C 1-4 and ring A may be selected from pyrrole, thiophene, pyridine, and phenyl, which may be optionally substituted, and when substituted, each may be selected from deuterium, halogen, unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Alkoxy, unsubstituted C 1-4 Haloalkyl and unsubstituted C 1-4 haloalkoxy; Ring B may be selected from unsubstituted or substituted 6-membered monocyclic nitrogen-containing heterocyclyl, unsubstituted or substituted 7-membered bicyclic nitrogen-containing heterocyclyl, and unsubstituted or substituted 8-membered bicyclic nitrogen-containing heterocyclyl; Ring C may be selected from pyrrole, thiophene, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, and phenyl; R 1a is hydrogen, deuterium, unsubstituted C 2-4 Alkyl, substituted C 1-4 Alkyl Unsubstituted C 2-4 Alkenyl, unsubstituted C 1-4 Haloalkyl, unsubstituted C 1-4 Hydroxyalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl, substituted monocyclic C 3-6 Cycloalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, Substituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), unsubstituted monocyclic C 3-6Cycloalkyl (unsubstituted C 2-4 alkenyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl), and the substitution C 1-4 Alkyl is a monocyclic C 3-6 Cycloalkyl, Substituted Bicyclic C 5-8 Cycloalkyl, substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl) is independently substituted by one or more substituents selected from deuterium and halogen; R 1b is hydrogen, unsubstituted C 1-4 Alkyl or unsubstituted C 1-4 may be haloalkyl or R 1a and R 1b is R 1a and R 1b may be combined with the carbon to which it is attached to form an unsubstituted or substituted monocyclic 3- to 4-membered cycloalkyl or an unsubstituted or substituted monocyclic 4- to 5-membered heterocyclyl, each of which may be selected from the group consisting of halogen, unsubstituted C 1-3 Alkyl and unsubstituted C 1-3 haloalkyl, where R 1b If is hydrogen, R 1a is deuterium, unsubstituted C 2-4 Alkyl, substituted C 1-4 Alkyl Unsubstituted C 2-4 Alkenyl, unsubstituted C 1-4 Haloalkyl, unsubstituted C 1-4 Hydroxyalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl, substituted monocyclic C 3-6 Cycloalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, Substituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C1-4 alkyl), unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl), and the substitution C 1-4 The alkyl may be substituted by one or more deuterium atoms and is a monocyclic C 3-6 Cycloalkyl, Substituted Bicyclic C 5-8 Cycloalkyl, substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl) may be independently substituted by one or more substituents selected from deuterium and halogen; 2 and R 3 are independently hydrogen, deuterium, or unsubstituted C 1-4 can be alkyl or R 2 and R 3 is R 2 and R 3 Together with the carbon to which it is attached, it forms an unsubstituted or substituted monocyclic C 3-6 m can be 0, 1, or 2; n can be 0, 1, or 2; and each R 3a are independently deuterium, halogen, or unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Haloalkyl, Cyano-Substituted C 1-4 Alkyl and unsubstituted monocyclic C 3-6 cycloalkyl, and each R 3b are independently deuterium, halogen, or unsubstituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl, unsubstituted C 2-4 Alkenyl, unsubstituted C 1-4 Haloalkyl, Unsubstituted Monocyclic C 3-6 Cycloalkyl and unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), R 4 is -C(=O)NR 5 R 6 R5 is hydrogen or unsubstituted C 1-4 may be alkyl, R 6 is hydrogen, unsubstituted C 1-4 Alkyl, substituted C 1-4 Alkyl, unsubstituted monocyclic C 3-6 Cycloalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), or unsubstituted bicyclic C 5-8 Cycloalkyl (unsubstituted C 1-4 alkyl), and may be substituted C 1-4 The alkyl is substituted with one or more deuterium atoms.

[0076] In some embodiments, ring A can be pyrrole. In other embodiments, ring A can be thiophene. In still other embodiments, ring A can be pyridine. In still other embodiments, ring A can be phenyl. Each of pyrrole, thiophene, pyridine, and phenyl can be substituted with deuterium, halogen (e.g., F, Cl, or Br), unsubstituted C, or aryl. 1-4 Alkyl (such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and tert-butyl), unsubstituted C 1-4 Alkoxy (e.g., methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy), unsubstituted C 1-4 Haloalkyl (including -CF3, -CCl3, -CHF2, -C(CH3)F2, -CHCl2, -CH2F, -CH(CH3)F, -CH2CF3, -CH2Cl, -CH2CH2F, -CH2CH2Cl, -CH2CH2CH2F, and -CH2CH2CH2Cl), and unsubstituted C 1-4It may be substituted one or more times with a moiety (such as 1, 2, or 3 moieties) independently selected from haloalkoxy (such as -OCF3, -OCCl3, -OCHF2, -OC(CH3)F2, -OCHCl2, -OCH2F, -OCH(CH3)F, -OCH2CF3, -OCH2Cl, -OCH2CH2F, -OCH2CH2Cl, -OCH2CH2CH2F, and -OCH2CH2CH2Cl). Examples of rings for ring A include the following: [ka] where the asterisk indicates the point of attachment to the morpholinone ring of formula (I). For example, ring A is [ka]

[0033] When the compound of formula (I), or a pharma- ceutically acceptable salt thereof, has the following structure: [ka] In some embodiments, ring A can have the following structure: [ka] In other embodiments, ring A can be: [ka] It could be.

[0077] In some embodiments, Y 1 can be O, such that formula (I) can have the structure of formula (Ia), including pharma- ceutically acceptable salts thereof. In other embodiments, Y 1 can be CH2 such that formula (I) can have the structure of formula (Ib), including pharma- ceutically acceptable salts thereof. In yet other embodiments, Y 1 CR Y1 R Y2 R may be, such that formula (I) can have the structure of formula (Ic) (including pharma- ceutically acceptable salts) or the structure of formula (Id) (including pharma- ceutically acceptable salts). Y1 and RY2 are independently deuterium, halogen (such as fluoro or chloro), unsubstituted C 1-4 Alkyl (e.g., methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and tert-butyl), unsubstituted C 1-4 haloalkyl (e.g., -CF3, -CCl3, -CHF2, -C(CH3)F2, -CHCl2, -CH2F, -CH(CH3)F, -CH2CF3, -CH2Cl, -CH2CH2F, -CH2CH2Cl, -CH2CH2CH2F, and -CH2CH2CH2Cl, etc.), or unsubstituted monocyclic C 3-6 It can be cycloalkyl (eg, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl). [ka]

[0078] A variety of rings or heterocycles may be present in Ring B. The heterocyclyl of Ring B may be a monocyclic or bicyclic ring. When Ring B is a bicyclic ring, the rings may be linked in a fused fashion. In other cases, when Ring B is a bicyclic ring, the rings may be linked in a fused fashion. As provided herein, Ring B may contain a ring nitrogen. Additional ring heteroatoms such as additional nitrogen, oxygen, and / or sulfur may be present in Ring B. In some embodiments, Ring B may be an unsubstituted 6-membered monocyclic nitrogen-containing heterocyclyl. In other embodiments, Ring B may be a substituted 6-membered monocyclic nitrogen-containing heterocyclyl. In still other embodiments, Ring B may be an unsubstituted 7-membered bicyclic nitrogen-containing heterocyclyl. In still yet other embodiments, Ring B may be a substituted 7-membered bicyclic nitrogen-containing heterocyclyl. In some embodiments, Ring B may be an unsubstituted 8-membered bicyclic nitrogen-containing heterocyclyl. In other embodiments, Ring B can be a substituted 8-membered bicyclic nitrogen-containing heterocyclyl. Exemplary Ring B groups include the following: [ka] In some embodiments, ring B includes, but is not limited to, [ka] It could be.

[0079] In some embodiments, ring B can be unsubstituted when m is 0. In other embodiments, ring B can be unsubstituted when m is 1. 3a In yet other embodiments, ring B can be substituted with R 3a For example, each R 3a are independently deuterium, halogen, or unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Haloalkyl, Cyano-Substituted C 1-4 Alkyl or unsubstituted monocyclic C 3-6 Suitable halogens, unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Haloalkyl, Cyano-Substituted C 1-4 Alkyl and unsubstituted monocyclic C 3-6 Cycloalkyl is described herein and includes chloro, fluoro, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, -CF3, -CHF2, -C(CH3)F2, -CHCl2, -CH2F, -CH(CH3)F, -CH2CF3, -CH2Cl, -CH2CH2F, -CH2CH2Cl, -CH2CH2CH2F, -CH2CH2CH2Cl, -CH2CN, -CH2CH2CN, -CH2CH2CH2CN, -CH2CH2CH2CH2CN, -CH(CN)CH3, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0080] In some embodiments, R 4can be a C-amide. In some embodiments, ring C can be a pyrrole. In other embodiments, ring C can be a thiophene. In still other embodiments, ring C can be a thiazole. In still other embodiments, ring C can be a pyridine. In some embodiments, ring C can be a pyridazine. In other embodiments, ring C can be a pyrimidine. In still other embodiments, ring C can be a pyrazine. Exemplary rings for ring C are as follows: [ka] In some embodiments, ring C is [ka] For the structure shown for ring C, the bond to the right of the ring can be R 4 ,for example, [ka] Concatenate to.

[0081] Additionally, moieties can be present in Ring C. In some embodiments, Ring C is R 3b and each R 3b are independently deuterium, halogen, or unsubstituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl, unsubstituted C 2-4 Alkenyl, unsubstituted C 1-4 Haloalkyl, Unsubstituted Monocyclic C 3-6 Cycloalkyl and unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4In some embodiments, Ring C can be selected from deuterium, F, Cl, Br, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, ethenyl, propenyl, butenyl, -CF3, -CHF2, -C(CH3)F2, -CHCl2, -CH2F, -CH(CH3)F, -CH2CF3, -CH2Cl, -CH2CH2F, -CH2CH2Cl, -CH2CH2CH2F, -CH2CH2CH2Cl, -CD3, -CD2H, -CDH2, -CHDCH3, -CH2CHD2, -CH2CH2D, -CHDCHD2, -CHDCH2D, -CD2CHD2, -CD2CH2D, -CH2CD3, -CD2CH3-CD2CD3, cyclopropyl, cyclobutyl, cyclopentyl ...

[0043] In one embodiment, the cycloalkyl group may be substituted one or more times (such as 1, 2, or 3 times) with a moiety independently selected from cyclohexyl, cyclopropyl-CH2-, cyclobutyl-CH2-, cyclopentyl-CH2-, cyclohexyl-CH2-, cyclopropyl-CH2CH2-, cyclobutyl-CH2CH2-, cyclopentyl-CH2CH2-, cyclohexyl-CH2CH2-, cyclopropyl-CH2CH2CH2-, cyclobutyl-CH2CH2CH2-, cyclopentyl-CH2CH2CH2-, cyclohexyl-CH2CH2CH2-, cyclopropyl-CH2CH2CH2-, cyclobutyl-CH2CH2CH2-, cyclopentyl-CH2CH2CH2-, cyclohexyl-CH2CH2CH2-, cyclopropyl-CH2CH2CH2CH2-, cyclobutyl-CH2CH2CH2CH2-, cyclopentyl-CH2 ... and cyclohexyl-CH2CH2CH2CH2-.

[0082] As provided herein, ring A and ring C can be substituted. In some embodiments, both ring A and ring C can be substituted. For example, both ring A and ring C can be monosubstituted. In some embodiments, ring A can be substituted with deuterium, halogen, unsubstituted C. 1-4 Alkyl, unsubstituted C 1-4 Alkoxy, unsubstituted C 1-4 Haloalkyl or unsubstituted C 1-4 Ring C may be substituted (such as monosubstituted) with haloalkoxy, and ring C may be substituted with deuterium, halogen, unsubstituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl, unsubstituted C 2-4 Alkenyl, unsubstituted C1-4 Haloalkyl, Unsubstituted Monocyclic C 3-6 Cycloalkyl or unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 In some embodiments, ring A can be substituted (such as monosubstituted) with deuterium, halogen, or unsubstituted C 1-4 The ring C may be substituted (such as monosubstituted) with alkyl, and the ring C may be substituted with deuterium, halogen, unsubstituted C 1-4 Alkyl or deuterium substituted C 1-4 In some embodiments, ring A is substituted (e.g., monosubstituted) with alkyl. In some embodiments, ring A is substituted (e.g., monosubstituted) with alkyl. 1-4 and ring C may be substituted (such as monosubstituted) with alkyl, and ring C may be halogen or unsubstituted C 1-4 In some embodiments, ring A can be substituted (such as monosubstituted) with alkyl. In some embodiments, ring A can be substituted (such as monosubstituted) with deuterium, halogen, unsubstituted C 1-4 Alkyl and unsubstituted C 1-4 ring C can be pyridine; n can be 1 or 2; and each R 3b are independently deuterium, halogen, or unsubstituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl and unsubstituted C 1-4 In other embodiments, ring A can be selected from deuterium, halogen, unsubstituted C 1-4 Alkyl and unsubstituted C 1-4 ring C can be pyridine; n can be 1 or 2; and each R 3b are independently deuterium, halogen, or unsubstituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl and unsubstituted C 1-4 In some embodiments, ring A can be selected from deuterium, halogen, unsubstituted C 1-4 Alkyl and unsubstituted C 1-4 substituted one or more times with a moiety independently selected from alkoxy [ka] Ring C can be pyridine, n can be 1 or 2, and each R 3b are independently deuterium, halogen, or unsubstituted C 1-4 Alkyl, deuterium-substituted C 1-4 Alkyl and unsubstituted C 1-4 haloalkyl; halogen, unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Alkoxy, unsubstituted C 1-4 Haloalkyl, unsubstituted C 1-4 Haloalkoxy, Deuterium-Substituted C 1-4 Alkyl, unsubstituted C 2-4 Alkenyl, unsubstituted monocyclic C 3-6 Cycloalkyl and unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4Examples of alkyl groups are described herein and include deuterium, F, Cl, Br, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, ethenyl, propenyl, butenyl, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, -CF3, -CHF2, -C(CH3)F2, -CHCl2, -CH2F, -CH(CH 3)F, -CH2CF3, -CH2Cl, -CH2CH2F, -CH2CH2Cl, -CH2CH2CH2F, -CH2CH2CH2Cl, -OCF3, -OCCl3, -OCHF2, -OC(CH3)F2, -OCHCl 2, -OCH2F, -OCH(CH3)F, -OCH2CF3, -OCH2Cl, -OCH2CH2F, -OCH2CH2Cl, -OCH2CH2CH2F, -OCH2CH2CH2Cl, -CD3, -CD2H, -CDH2 , -CHDCH3, -CH2CHD2, -CH2CH2D, -CHDCHD2, -CHDCH2D, -CD2CHD2, -CD2CH2D, -CH2CD3, -CD2CH3-CD2CD3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropyl-CH2-, cyclobutyl-CH2-, cyclopentyl-CH2-, cyclohexyl-CH2-, cyclopropyl-CH2CH2-, cyclobutyl-CH2CH2-, cyclo Examples include cyclopentyl-CH2CH2-, cyclohexyl-CH2CH2-, cyclopropyl-CH2CH2CH2-, cyclobutyl-CH2CH2CH2-, cyclopentyl-CH2CH2CH2-, cyclohexyl-CH2CH2CH2-, cyclopropyl-CH2CH2CH2-, cyclobutyl-CH2CH2CH2-, cyclopentyl-CH2CH2CH2-, cyclohexyl-CH2CH2CH2-, cyclopropyl-CH2CH2CH2CH2-, cyclobutyl-CH2CH2CH2CH2-, cyclopentyl-CH2CH2CH2CH2-, and cyclohexyl-CH2CH2CH2CH2-. In some embodiments, ring A can be monosubstituted with F, Cl, Br, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, or tert-butyl, and ring C can be monosubstituted with F, Cl, Br, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, or tert-butyl.

[0083] In some embodiments, ring A is [ka] and ring B is [ka] and ring C may be [ka] In other embodiments, ring A can be: [ka] and ring B is [ka] and ring C may be [ka] In yet other embodiments, ring A can be: [ka] and ring B is [ka] and ring C may be [ka] In still other embodiments, ring A can be: [ka] and ring B is [ka] and ring C may be [ka] It could be.

[0084] As provided herein, -C(=O)NR 5 R 6 The group is attached to Ring C. In some embodiments, R 5 is ring C is -C(=O)NHR 6 In other embodiments, R may be substituted with 5 is unsubstituted C 1-4 It can be alkyl, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and tert-butyl. In some embodiments, ring C is -C(=O)N(CH3)R 6 may be substituted with

[0085] -C(=O)NR 5 R 6 In addition, ring C is R 3b In some embodiments, when n is 0, ring B can include one or two other groups such as -C(=O)NR 5 R 6 In other embodiments, when n is 1, ring B can be unsubstituted except for one R 3b In yet another embodiment, when n is 2, ring B can be substituted with two R 3b As provided herein, each R 3b are independently deuterium, halogen, or unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Haloalkyl, or unsubstituted monocyclic C 3-6 cycloalkyl. Each R 3b Exemplary moieties can be deuterium, chloro, fluoro, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, -CF3, -CHF2, -C(CH3)F2, -CHCl2, -CH2F, -CH(CH3)F, -CH2CF3, -CH2Cl, -CH2CH2F, -CH2CH2Cl, -CH2CH2CH2F, -CH2CH2CH2Cl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0086] In some embodiments, R 6 is an unsubstituted monocyclic C 3-6 In other embodiments, R 6 is an unsubstituted bicyclic C 5-8 In yet other embodiments, R 6 is an unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 In still other embodiments, R 6 is an unsubstituted bicyclic C 5-8 Cycloalkyl (unsubstituted C 1-4 R can be any alkyl group. 6 Possible monocyclic rings for 3-6 Cycloalkyl and / or R 6 Unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 The alkyl portion can be cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. 6 Bicyclic C 5-8 Cycloalkyl and / or R 6 Unsubstituted bicyclic C 5-8 Some examples of cycloalkyl include bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, and bicyclo[2.2.2]octane. In some embodiments, R 6 is an unsubstituted bicyclic C 5-8 Cycloalkyl-CH3-, bicyclic C 5-8 Examples of cycloalkyls are described herein.

[0087] As provided herein, the morpholinone ring of Formula (I) can be unsubstituted or substituted. In some embodiments, R 1a can be hydrogen. In some embodiments, R 1a can be deuterium. In yet other embodiments, R 1a is an unsubstituted C such as ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and tert-butyl. 2-4In still other embodiments, R 1a is a substitution C that can be replaced by one or more deuterium atoms 1-4 For example, R 1a can be -CD3, -CD2H, -CDH2, -CHDCH3, -CH2CHD2, -CH2CH2D, -CHDCHD2, -CHDCH2D, -CD2CHD2, -CD2CH2D, -CH2CD3, -CD2CH3-CD2CD3, -CD2CD2CD3, or -CD2CD2CD2CD3. 1a is unsubstituted C 2-4 Exemplary unsubstituted C 2-4 Alkenyl includes ethenyl, propenyl, 2-methyl-propenyl, and butenyl. In other embodiments, R 1a is C 1-4 For example, R 1a is unsubstituted C 1-4 When R is haloalkyl, 1a can be -CF3, -CHF2, -C(CH3)F2, -CHCl2, -CH2F, -CH(CH3)F, -CH2CF3, -CH2CHF2, -CH2Cl, -CH2CH2F, -CH2CH2Cl, -CH2CH2CH2F, and -CH2CH2CH2Cl. 1a is an unsubstituted C such as -CH2-OH, -CH2CH2-OH, -CH2CH2CH2-OH, and -CH2CH2CH2CH2-OH. 1-4 In still other embodiments, R 1a is an unsubstituted monocyclic C 3-6 In some embodiments, R 1a is a monocyclic C substituted with one or more substituents (such as 1, 2, 3, 4, 5, or 6 substituents) selected from deuterium and halogen; 3-6 In other embodiments, R 1a is an unsubstituted bicyclic C 5-8 In yet other embodiments, R 1ais a bicyclic C substituted with one or more substituents selected from deuterium and halogen; 5-8 In still other embodiments, R 1a is an unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 In some embodiments, R 1a is an unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 In other embodiments, R 1a is a substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 In some embodiments, R 1a is a deuterium-substituted monocyclic C 3-6 In other embodiments, R 1a is a deuterium-substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 In yet other embodiments, R 1a is a deuterium-substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 R can be any alkenyl. 1a Deuterium-substituted monocyclic C 3-6 Cycloalkyl, Deuterium-Substituted Monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 Alkyl) or deuterium-substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 In other embodiments, when R is an alkyl group, one or more hydrogens (e.g., 1, 2, 3, 4, 5, or 6 hydrogens) can be replaced with deuterium. 1a is a halogen-substituted monocyclic C 3-6 In other embodiments, R 1a is a halogen-substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 In yet other embodiments, R 1a is a halogen-substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 R can be any alkenyl. 1aHowever, halogen-substituted monocyclic C 3-6 Cycloalkyl, halogen-substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 Alkyl) or halogen-substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl), one or more hydrogens (e.g., 1, 2, 3, 4, 5, or 6 hydrogens) can be replaced with halogen. 1a is a monocyclic C substituted with both deuterium(s) and halogen(s); 3-6 In other embodiments, R 1a is a monocyclic C substituted with both deuterium(s) and halogen(s); 3-6 Cycloalkyl (unsubstituted C 1-4 In yet other embodiments, R 1a is a monocyclic C substituted with both deuterium(s) and halogen(s); 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl). 3-6 Cycloalkyl 、 monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), and monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 Possible cycloalkyls that may be present in the bicyclic C alkyl group include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. 5-8 Exemplary bicyclic C groups that may be present in a cycloalkyl 5-8 Cycloalkyl includes, but is not limited to, bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[3.2.1]octane, and bicyclo[2.2.2]octane. 3-6 Cycloalkyl C 1-4 Alkyl (unsubstituted C 1-4 Alkyl) and monocyclic C 3-6 Cycloalkyl C 2-4 Alkenyl (unsubstituted C 2-4Alkenyl) may be straight or branched chain. 3-6 Exemplary cycloalkyl groups 1-4 Alkyl (unsubstituted C 1-4 Alkyl) includes -CH-, -CHCH-, -CHCHCH-, and -CHCHCHCHCH-. 3-6 Exemplary cycloalkyl groups 2-4 Alkenyl (unsubstituted C 2-4 Alkenyl) includes -CH=CH2-, -CH=CHCH2-, -CH2CH=CH2-, -CH=C=CH2-, -CH=CHCH2CH2-, -CH2CH=CHCH2-, and -CH2CH2CH=CH-.

[0088] In some embodiments, R 1b can be hydrogen. In other embodiments, R 1b is an unsubstituted C alkyl group such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and tert-butyl. 1-4 In yet other embodiments, R 1b is an unsubstituted C, including those described herein. 1-4 R can be haloalkyl. 1b Non-substituted C 1-4 Examples of haloalkyl include -CF, -CCl, -CHF, -C(CH)F, -CHCl, -CHF, -CH(CH)F, -CHCF, -CHCl, -CHCHF, -CHCHCl, -CHCHCHF, -CHCHCHF, and -CHCHCHCHCl. ​​In some embodiments, R 1a If is hydrogen, R 1b is hydrogen, unsubstituted C 2-4 Alkyl or unsubstituted C 1-4 It may be a haloalkyl.

[0089] R 1a If is a non-hydrogen moiety, R 1a and R 1b The carbon to which R is attached may be a chiral center. For example, R 1a is unsubstituted C 2-4is alkyl, R 1b can be hydrogen, R 1a and R 1b The carbon to which R is attached may be in the (R) or (S) configuration. 1a may be a hydrogen moiety, R 1b may be non-hydrogen, R 1a and R 1b The carbon to which R is attached may be in the (R) configuration, such that the compound of formula (I) has the structure of the compound of formula (Id). 1a may be a hydrogen moiety, R 1b may be non-hydrogen, R 1a and R 1b The carbon to which R is attached may be in the (S) configuration, such that the compound of formula (I) has the structure of the compound of formula (Ie). 1b is hydrogen, R 1a is deuterium, unsubstituted C 2-4 Alkyl, substituted C 1-4 Alkyl Unsubstituted C 2-4 Alkenyl, unsubstituted C 1-4 Haloalkyl, unsubstituted C 1-4 Hydroxyalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl, substituted monocyclic C 3-6 Cycloalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, Substituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl). In other embodiments, R 1b is hydrogen, R 1a is deuterium, unsubstituted C 2-4 Alkyl, substituted C 1-4 Alkyl Unsubstituted C 2-4 Alkenyl, unsubstituted C1-4 Haloalkyl, unsubstituted C 1-4 Hydroxyalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, Substituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 alkenyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 2-4 In yet other embodiments, R 1b is hydrogen, R 1a is deuterium, unsubstituted C 2-4 Alkyl, substituted C 1-4 Alkyl Unsubstituted C 2-4 Alkenyl, unsubstituted C 1-4 Haloalkyl and unsubstituted C 1-4 In still yet other embodiments, R 1b is hydrogen, R 1a is unsubstituted C 2-4 In some embodiments, R 1b is hydrogen, R 1a is unsubstituted C 1-4 In some embodiments, R 1b is hydrogen, R 1a is an unsubstituted monocyclic C 3-6 In other embodiments, R 1b is hydrogen, R 1a is a substituted monocyclic C 3-6 In yet other embodiments, R 1b is hydrogen, R 1a is an unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 In still other embodiments, R 1b is hydrogen, R 1a is a substituted monocyclic C3-6 Cycloalkyl (unsubstituted C 1-4 alkyl). [ka]

[0090] As provided herein, R 1a and R 1b is R 1a and R 1b may be taken together with the carbon to which it is attached to form an unsubstituted or substituted monocyclic 3-4 membered cycloalkyl or an unsubstituted or substituted monocyclic 4-5 membered heterocyclyl, such that the monocyclic ring formed is spiro-connected to the morpholinone ring of formula (I). 1a and R 1b is R 1a and R 1b may be taken together with the carbon to which it is attached to form an unsubstituted monocyclic 3-4 membered cycloalkyl. In other embodiments, the monocyclic 3-4 membered cycloalkyl is selected from the group consisting of halogen, unsubstituted C 1-3 Alkyl and unsubstituted C 1-3 R can be substituted with one or more (such as 1, 2, or 3) moieties independently selected from haloalkyl. 1a and R 1b But R 1a and R 1b may be taken together with the carbon to which it is attached to form a substituted monocyclic 3-4 membered cycloalkyl. 1a and R 1b is R 1a and R 1b may be taken together with the carbon to which it is attached to form an unsubstituted 4-membered heterocyclyl. 1a and R 1b But R 1a and R 1b Together with the carbon to which it is attached, halogen, unsubstituted C 1-3 Alkyl and unsubstituted C 1-3 A substituted 4-membered heterocyclyl can be formed, substituted with one or more (such as 1, 2, or 3) moieties independently selected from haloalkyl.

[0091] Exemplary moieties that may be present on the substituted 3-4 membered cycloalkyl and / or substituted monocyclic 4-5 membered heterocyclyl include fluoro, chloro, methyl, ethyl, n-propyl, iso-propyl, -CF3, -CCl3, -CHF2, -C(CH3)F2, -CHCl2, -CH2F, CH(CH3)F, -CH2CF3, -CH2Cl, -CH2CH2F, -CH2CH2Cl, -CH2CH2CH2F, and -CH2CH2CH2Cl. A non-limiting list of 3-4 membered cycloalkyl and monocyclic 4-5 membered heterocyclyl includes the following: cyclopropyl, cyclobutyl, oxetane, thietane, azetidine, tetrahydrofuran, tetrahydrothiophene, and pyrrolidine. In some embodiments, R 1a and R 1b is R 1a and R 1b together with the carbon to which it is bonded, [ka] may form a cyclic group selected from:

[0092] In some embodiments, R 2 and R 3 Each can be hydrogen. In other embodiments, R 2 and R 3 Each of R can be deuterium. 2 and R 3 are unsubstituted C 1-4 For example, R 2 and R 3 may be independently selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and tert-butyl. 2 and R 3 can be deuterium, R 2 and R 3 The other is hydrogen or unsubstituted C 1-4 In some embodiments, R 2 and R 3 is R2 and R 3 Together with the carbon to which it is attached, it forms an unsubstituted or substituted monocyclic C 3-6 For example, R 2 and R 3 is R 2 and R 3 together with the carbon to which it is attached can form an unsubstituted or substituted cyclopropyl, unsubstituted or substituted cyclobutyl, unsubstituted or substituted cyclopentyl, or unsubstituted or substituted cyclohexyl.

[0093] In some embodiments, the compound of formula (I), or a pharma- ceutically acceptable salt thereof, is 1 is O (oxygen), CH2, or CHR Y1 R Y1 is deuterium, halogen, or unsubstituted C 1-4 and ring A may be selected from pyrrole, thiophene, pyridine, and phenyl, which may be optionally substituted, and when substituted, each may be selected from deuterium, halogen, unsubstituted C 1-4 Alkyl and unsubstituted C 1-4 haloalkyl; Ring B may be selected from unsubstituted or substituted 6-membered monocyclic nitrogen-containing heterocyclyl, unsubstituted or substituted 7-membered bicyclic nitrogen-containing heterocyclyl, and unsubstituted or substituted 8-membered bicyclic nitrogen-containing heterocyclyl; Ring C may be selected from pyrrole, thiophene, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, and phenyl, which may be optionally substituted and, when substituted, each may be selected from deuterium, halogen, unsubstituted C 1-4 Alkyl, unsubstituted C 2-4 Alkenyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), and unsubstituted C 1-4 haloalkyl; R 1a is hydrogen, unsubstituted C 2-4 Alkyl, unsubstituted C2-4 Alkenyl, unsubstituted C 1-4 Haloalkyl, unsubstituted C 1-4 Hydroxyalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkenyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkenyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl) may be substituted with one or more deuterium atoms; R 1b is hydrogen, unsubstituted C 1-4 Alkyl or unsubstituted C 1-4 may be haloalkyl or R 1a and R 1b is R 1a and R 1b may be combined with the carbon to which it is attached to form an unsubstituted or substituted monocyclic 3- to 4-membered cycloalkyl or an unsubstituted or substituted monocyclic 4- to 5-membered heterocyclyl, each of which may be selected from the group consisting of halogen, unsubstituted C 1-3 Alkyl and unsubstituted C 1-3 haloalkyl, where R 1a If is hydrogen, R 1b is hydrogen, unsubstituted C 2-4 Alkyl or unsubstituted C 1-4 R may be haloalkyl; 2 and R 3 are independently hydrogen, deuterium, or unsubstituted C 1-4 can be alkyl or R 2 and R 3 is R 2 and R 3 Together with the carbon to which it is attached, it forms an unsubstituted or substituted monocyclic C3-6 cycloalkyl, m can be 0 or 1, n can be 0, 1, or 2, R 3a is deuterium, halogen, unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Haloalkyl, or unsubstituted monocyclic C 3-6 R may be cycloalkyl; 3b is deuterium, halogen, unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Haloalkyl, or unsubstituted monocyclic C 3-6 may be cycloalkyl, R 4 is -C(=O)NR 5 R 6 R 5 is hydrogen or unsubstituted C 1-4 may be alkyl, R 6 is hydrogen, unsubstituted C 1-4 Alkyl, substituted C 1-4 Alkyl, unsubstituted monocyclic C 3-6 Cycloalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), or unsubstituted bicyclic C 5-8 Cycloalkyl (unsubstituted C 1-4 alkyl), and may be substituted C 1-4 The alkyl is substituted with one or more deuterium atoms.

[0094] In some embodiments, the compound of formula (I), or a pharma- ceutically acceptable salt thereof, is 1 is O (oxygen), CH2, or CHR Y1 R Y1 is deuterium, halogen, or unsubstituted C 1-4 and ring A may be selected from pyrrole, thiophene, pyridine, and phenyl, which may be optionally substituted, and when substituted, each may be selected from deuterium, halogen, unsubstituted C 1-4 Alkyl and unsubstituted C 1-4haloalkyl; Ring B may be selected from unsubstituted or substituted 6-membered monocyclic nitrogen-containing heterocyclyl, unsubstituted or substituted 7-membered bicyclic nitrogen-containing heterocyclyl, and unsubstituted or substituted 8-membered bicyclic nitrogen-containing heterocyclyl; Ring C may be selected from pyrrole, thiophene, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, and phenyl, which may be optionally substituted and, when substituted, each may be selected from deuterium, halogen, unsubstituted C 1-4 Alkyl, unsubstituted C 2-4 Alkenyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), and unsubstituted C 1-4 haloalkyl; R 1a is hydrogen, unsubstituted C 2-4 Alkyl, unsubstituted C 2-4 Alkenyl, unsubstituted C 1-4 Haloalkyl, unsubstituted C 1-4 Hydroxyalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkenyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkenyl), and substituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl) may be substituted with one or more deuterium atoms; R 1b is hydrogen, unsubstituted C 1-4 Alkyl or unsubstituted C 1-4 may be haloalkyl or R 1a and R 1b is R 1a and R 1bmay be combined with the carbon to which it is attached to form an unsubstituted or substituted monocyclic 3- to 4-membered cycloalkyl or an unsubstituted or substituted monocyclic 4- to 5-membered heterocyclyl, each of which may be selected from the group consisting of halogen, unsubstituted C 1-3 Alkyl and unsubstituted C 1-3 haloalkyl, where R 1a If is hydrogen, R 1b is hydrogen, unsubstituted C 2-4 Alkyl or unsubstituted C 1-4 R may be haloalkyl; 2 and R 3 are independently hydrogen, deuterium, or unsubstituted C 1-4 can be alkyl or R 2 and R 3 is R 2 and R 3 Together with the carbon to which it is attached, it forms an unsubstituted or substituted monocyclic C 3-6 cycloalkyl, m can be 0 or 1, n can be 0, 1, or 2, R 3a is deuterium, halogen, unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Haloalkyl, or unsubstituted monocyclic C 3-6 may be cycloalkyl, R 3b is deuterium, halogen, unsubstituted C 1-4 Alkyl, unsubstituted C 1-4 Haloalkyl, or unsubstituted monocyclic C 3-6 may be cycloalkyl, R 4 is -C(=O)NR 5 R 6 R 5 is hydrogen or unsubstituted C 1-4 may be alkyl, R 6 is hydrogen, unsubstituted C 1-4 Alkyl, substituted C 1-4 Alkyl, unsubstituted monocyclic C 3-6 Cycloalkyl, Unsubstituted Bicyclic C 5-8 Cycloalkyl, unsubstituted monocyclic C 3-6 Cycloalkyl (unsubstituted C 1-4 alkyl), or unsubstituted bicyclic C5-8 Cycloalkyl (unsubstituted C 1-4 alkyl), and may be substituted C 1-4 The alkyl is substituted with one or more deuterium atoms.

[0095] Examples of compounds of formula (I) include the following: [ka] [ka] [ka] [ka] [ka] [ka] [ka] or a pharma- ceutically acceptable salt of any of the foregoing.

[0096] Further examples of compounds of formula (I) include the following: [ka] [ka] [ka] [ka] [ka] [ka] [ka] or a pharma- ceutically acceptable salt of any of the foregoing.

[0097] In some embodiments, the compound of formula (I) or a pharma- ceutically acceptable salt thereof is [ka] or a pharma- ceutically acceptable salt of any of the foregoing. In some embodiments, the compound of formula (I) or a pharma- ceutically acceptable salt thereof may not be provided in WO2022 / 222921, WO2022 / 223025, and / or WO2010 / 111626. In some embodiments, ring A may not be phenyl. In some embodiments, ring A may be [ka] In some embodiments, ring A cannot be phenyl. In some embodiments, ring C cannot be [ka] In some embodiments, ring C cannot be: [ka] In some embodiments, ring A and ring C cannot each be unsubstituted. In some embodiments, ring A cannot be unsubstituted and ring C cannot be substituted (e.g., mono-substituted). In other embodiments, ring A cannot be substituted (e.g., mono-substituted) and ring C cannot be unsubstituted.

[0098] synthesis Compounds of formula (I) may be prepared in various ways, as described herein. A general synthetic route for preparing compounds of formula (I) is shown and described herein, along with some examples of starting materials used to synthesize the compounds described herein. Additionally, for the purposes of the general synthetic route, the structures shown are appropriately protected as known by those skilled in the art, and the general structures are meant to include these protecting groups. The routes shown and described herein are illustrative only, and are not intended or should be construed to limit the scope of the claims in any manner. Those skilled in the art will recognize modifications of the disclosed synthesis and will be able to devise alternative routes based on the disclosure of this specification. All such modifications and alternative routes are within the scope of the claims. [ka] [ka]

[0099] Scheme 1 provides an exemplary method for preparing compounds of formula (I), including pharma- ceutically acceptable salts thereof. In Scheme 1, separation can be achieved by methods known to those skilled in the art, such as supercritical fluid chromatography, to provide compounds of formula (I), where the compound designated with an asterisk is in the (R) or (S) configuration.

[0100] Pharmaceutical Compositions Some embodiments described herein relate to pharmaceutical compositions that may include an effective amount of a compound described herein (e.g., a compound described herein, or a pharma- ceutically acceptable salt thereof) and a pharma- ceutically acceptable carrier, excipient, or combination thereof. The pharmaceutical compositions described herein are suitable for human and / or veterinary use.

[0101] As used herein, a "carrier" refers to a compound that facilitates the uptake of a compound into cells or tissues. For example, but not limited to, dimethyl sulfoxide (DMSO) is a commonly used carrier that facilitates the uptake of many organic compounds into cells or tissues of a subject.

[0102] As used herein, "diluent" refers to an ingredient in a pharmaceutical composition that lacks pharmacological activity but may be pharma- ceutically necessary or desirable. For example, a diluent may be used to increase the volume of a potent drug whose mass is too small to manufacture and / or administer. It may also be a liquid for dissolving a drug to be administered by injection, ingestion, or inhalation. A common form of diluent in the art is a buffered aqueous solution, such as, but not limited to, phosphate buffered saline, which mimics the composition of human blood.

[0103] As used herein, "excipient" refers to an inert substance added to a pharmaceutical composition to provide the composition with, but is not limited to, bulk, consistency, stability, binding ability, lubricity, disintegration ability, etc. A "diluent" is a type of excipient.

[0104] Appropriate formulation depends on the route of administration selected. The techniques for formulating and administering the compounds described herein are known to those skilled in the art. In the art, there are multiple techniques for administering compounds, including but not limited to oral, rectal, topical, aerosol, injection, inhalation, and parenteral delivery, including intramuscular, subcutaneous, intravenous, intramedullary injection, intrathecal, direct intraventricular, intraperitoneal, intranasal, and intraocular injection. Pharmaceutical compositions will generally be adjusted to the specific intended route of administration.

[0105] The compounds may also be administered in a local rather than systemic manner, for example, by injecting the compound directly into the infected area, often in a depot or sustained release formulation. Furthermore, the compounds may be administered in a targeted drug delivery system, for example, in liposomes coated with tissue-specific antibodies. The liposomes may be targeted to and taken up selectively by organs.

[0106] The pharmaceutical compositions disclosed herein may be manufactured in a manner known per se, for example by conventional mixing, dissolving, granulating, dragee-making, pulverizing, emulsifying, encapsulating, entrapping or tabletting processes. As described herein, the compounds used in the pharmaceutical compositions may be provided as salts having pharma- ceutically compatible counterions.

[0107] How to use Some embodiments described herein relate to methods for treating a cancer described herein, which may include administering an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) to a subject having a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) in the manufacture of a medicament for treating a cancer described herein. Still other embodiments described herein relate to a pharmaceutical composition comprising an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) to treat a cancer described herein.

[0108] Some embodiments described herein relate to methods for inhibiting the growth of a malignant growth or tumor, which may include contacting the growth or tumor with an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), wherein the malignant growth or tumor results from a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), in the manufacture of a medicament for inhibiting the growth of a malignant growth or tumor, wherein the malignant growth or tumor results from a cancer described herein. Yet other embodiments described herein relate to an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), for inhibiting malignant growth or tumor growth, wherein the malignant growth or tumor results from a cancer described herein.

[0109] Some embodiments described herein relate to methods for treating a cancer described herein, which may include contacting a malignant growth or tumor with an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) in a subject having a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) in the manufacture of a medicament for treating a cancer, which may include contacting a malignant growth or tumor resulting from a cancer described herein. Yet other embodiments described herein relate to an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), for treating a cancer, which may involve contacting a malignant growth or tumor, wherein the malignant growth or tumor is due to a cancer described herein.

[0110] Some embodiments described herein relate to a method for inhibiting the activity of PARP1, which may include providing an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), to a cancer cell derived from a cancer described herein. Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), in the manufacture of a medicament for inhibiting the activity of PARP1. Still other embodiments described herein relate to a pharmaceutical composition comprising an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), to inhibit the activity of PARP1. Some embodiments described herein relate to methods for inhibiting the activity of PARP1, which may include providing an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), to a cancer cell derived from a cancer described herein. Other embodiments described herein relate to methods for inhibiting the activity of PARP1, which may include contacting a cancer cell derived from a cancer described herein with an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), thereby inhibiting the activity of PARP1.

[0111] Some embodiments described herein relate to methods for treating cancers described herein, which may include inhibiting the activity of PARP1 using an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof). Other embodiments described herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), in the manufacture of a medicament for treating a cancer described herein by inhibiting the activity of PARP1. Still other embodiments described herein relate to a pharmaceutical composition comprising an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), to treat a cancer described herein by inhibiting the activity of PARP1. Some embodiments described herein relate to methods for treating cancer described herein, which may include contacting a cancer cell with an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), wherein the compound inhibits the activity of PARP1.

[0112] Some embodiments disclosed herein relate to a method for inhibiting the activity of PARP1, which may include providing an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), to a subject having a cancer described herein or a cancer cell derived from a cancer described herein. Other embodiments disclosed herein relate to the use of an effective amount of a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), in the manufacture of a medicament for inhibiting the activity of PARP1. Still other embodiments disclosed herein relate to a pharmaceutical composition comprising a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof), or a compound described herein (e.g., a compound of Formula (I), or a pharma- ceutically acceptable salt thereof) for inhibiting the activity of PARP1.

[0113] Examples of suitable cancers include, but are not limited to, cancers that are lung cancer, pancreatic cancer, colon cancer (e.g., colorectal cancer), myeloid leukemia (e.g., AML, CML, and CMML), thyroid cancer, myelodysplastic syndrome (MDS), bladder cancer, epidermal cancer, melanoma, breast cancer, prostate cancer, head and neck cancer (e.g., squamous cell carcinoma of the head and neck), ovarian cancer, brain cancer (e.g., gliomas such as glioblastoma multiforme), cancers of mesenchymal origin (e.g., fibrosarcoma and rhabdomyosarcoma), sarcoma, tetracarcinoma, nuroblastoma, renal cancer, liver cancer, non-Hodgkin's lymphoma, multiple myeloma, or anaplastic thyroid carcinoma.

[0114] As used herein, the terms "treat," "treating," "treatment," "therapeutic," and "therapy" do not necessarily mean a complete cure or abolition of a disease or condition. Any alleviation of any undesirable signs or symptoms of a disease or condition can be considered treatment and / or therapy to any degree. Furthermore, treatment can include actions that may worsen the subject's overall well-being or appearance.

[0115] As used herein, "subject" refers to an animal that is the object of treatment, observation, or experiment. "Animals" include cold-blooded and warm-blooded vertebrates, as well as invertebrates, such as fish, shellfish, reptiles, and especially mammals. "Mammals" include, but are not limited to, mice, rats, rabbits, guinea pigs, dogs, cats, sheep, goats, cows, horses, camels, non-human primates, such as monkeys, chimpanzees, and apes, and especially humans. In some embodiments, the subject may be a human, for example, a human subject aged 18 years or older.

[0116] The term "effective amount" is used to indicate the amount of an active compound or drug that induces the indicated biological or pharmaceutical response. For example, an effective amount of a compound may be the amount necessary to alleviate or ameliorate the symptoms of a disease or to prolong the survival of the subject being treated. This response may occur in a tissue, system, animal, or human, and includes the alleviation of signs or symptoms of the disease being treated. Determination of an effective amount is well within the capabilities of one of ordinary skill in the art in light of the disclosure provided herein. The effective amount of the compounds disclosed herein required as a dose will depend on the route of administration, the type of animal, including humans, being treated, and the physical characteristics of the particular animal under consideration. Dosages can be adjusted to achieve the desired effect, but will depend on factors such as body weight, diet, concomitant medications, and other factors that one of ordinary skill in the medical arts would recognize. EXAMPLES

[0117] Additional embodiments are disclosed in further detail in the following examples, which are in no way intended to limit the scope of the claims. [Table 1]

[0118] Example 1 Compounds A1, 1aa and 1ab [ka] [ka] To a solution of 1 (1 g, 5.98 mmol) and NaHCO3 (552.80 mg, 6.58 mmol) in EA (10 mL) and H2O (10 mL) was added 2-bromobutanoyl bromide (2.06 g, 8.97 mmol). The mixture was stirred at 25 °C for 16.5 h. The mixture was extracted with EA (3 × 30 mL). The combined organic phase was washed with brine (50 mL), dried over Na2SO4, and concentrated to give a residue. The residue was dissolved in N,N-dimethylformamide (10 mL) and K2CO3 (826.78 mg, 5.98 mmol) and added to the mixture at 25 °C. The mixture was stirred at 25 °C for 16 h. The solution was poured into ice water (30 mL). The resulting solid was collected by filtration and the cake was dried under high vacuum to give the crude product. The crude product was triturated with PE:EA (3:1) at 25° C. for 30 min and filtered to give compound 2 (1.01 g, 71.77% yield) as a white solid.

[0119] To a solution of 2 (1 g, 4.25 mmol) in THF (20 mL) was added LiAlH4 (322.69 mg, 8.50 mmol) at 0°C. The mixture was stirred at 0°C for 0.5 h. The mixture was cooled to 0°C. H2O (0.3 mL) was added dropwise to the mixture at 0°C, followed by 15% NaOH (0.3 mL) and H2O (0.9 mL). The mixture was stirred for 20 min and then filtered. The filtrate was dried over Na2SO4 and concentrated to give the crude product. The crude product was triturated with EA (20 mL) at 20°C for 30 min and then filtered. Compound 3 (440 mg, 47.45% yield) was obtained as a white solid.

[0120] To a solution of 3 (396.22 mg, 1.91 mmol) in dichloromethane (8 mL) and N,N-dimethylformamide (0.01 mL) was added SOCl2 (454.95 mg, 3.82 mmol, 277.41 uL) at 20°C. The mixture was stirred at 20°C for 2 h. The mixture was filtered. The filter cake was dried under high vacuum to give a residue which was stirred in EA (3 mL) for 1 h to form a slurry and then filtered. Compound 4 (420 mg, 97.34% yield) was obtained as a yellow solid.

[0121] To a solution of 4 (350 mg, 1.55 mmol) and N-methyl-5-piperazin-1-yl-pyridine-2-carboxamide (341.62 mg, 1.55 mmol) in acetonitrile (8 mL) was added N-N-diisopropylethylamine (1.62 mL) and NaBr (478.74 mg, 4.65 mmol) at 20° C. The mixture was stirred at 80° C. for 12 h. The mixture was filtered and the cake was dried under reduced pressure to give a residue (630 mg, 99.20% yield). The residue (100 mg) was purified by preparative HPLC to give pure 1A (19.4 mg, 19.4% yield) as a white solid. The residue (100 mg) was separated by SFC to give the two enantiomers: 1aa (13.3 mg, 26% yield) and 1ab (16.2 mg, 32% yield) as white solids. The absolute configurations of 1aa and 1ab remain to be determined. The relative configurations are shown above and the configurations are arbitrarily assigned.

[0122] LC / MS: The gradient was 5% B in 0.40 min and 5-95% B in 0.40-3.00 min, held at 95% B for 1.00 min, then 95-5% B in 0.01 min, and the flow rate was 1.0 mL / min. Mobile phase A was 0.04% trifluoroacetic acid in water, and mobile phase B was 0.02% trifluoroacetic acid in acetonitrile. The column used for chromatography was a Luna C18 50 x 2.0 mm column (5 um particles). The detection method was diode array (DAD) and evaporative light scattering (ELSD) detection. The MS mode was positive electrospray ionization. The MS range was 100-1000.

[0123] SFC: Column: Phenomenex Luna C18 75×30mm×3um; Mobile phase: [water (FA)-ACN]; B%: 15%-45%, &min.

[0124] Compound 1A: 1 H NMR:(400MHz,DMSO-d6) δ 0.99(br d,J=4.88Hz,3H) 1.66-1.91(m,2H) 2.54(br d,J=3.75Hz,4H) 2.68-2.89(m,3H) 3.32-3.39(m,4H) 3.43(br d,J=7.00Hz,2H) 4.41-4.59(m,1H) 6.75-7.07(m,3H) 7.25-7.54(m,1H) 7.64-7.99(m,1H) 8.09-8.51(m,3H) 10.46-10.81(m,1H).LCMS(ESI+):410.2[M+H] + , RT: 1.748 minutes.

[0125] Compound 1aa: 1H NMR(400MHz,DMSO-d6) δ 0.98(t,J=7.38Hz,3H) 1.67-1.89(m,2H) 2.47-2.49(m,2H) 2.51-2.53(m,2H) 2.78(d,J=4.88Hz,3H) 3.32(br s,4H) 3.42(s,2H) 4.48(dd,J=7.75,4.50Hz,1H) 6.82-6.94(m,3H) 7.37(dd,J=8.82,2.81Hz,1H) 7.82(d,J=8.75Hz,1H) 8.11-8.18(m,1H) 8.14(s,1H) 8.25(d,J=2.75Hz,1H) 8.39(q,J=4.50Hz,1H) 10.61(s,1H).LCMS(ESI+):410.1[M+H] + 、RT:1.721 points.

[0126] Compound 1ab: 1 H NMR(400MHz,DMSO-d6) δ 0.98(t,J=7.38Hz,3H) 1.68-1.87(m,2H) 2.52(br s,4H) 2.77(d,J=4.88Hz,3H) 3.34(br s,4H) 3.40-3.45(m,2H) 4.48(dd,J=7.75,4.50Hz,1H) 6.82-6.93(m,3H) 7.35-7.41(m,1H) 7.82(d,J=8.88Hz,1H) 8.24-8.27(m,1H) 8.35-8.42(m,1H) 10.58-10.64(m,1H).LCMS(ESI+):410.2[M+H] + 、RT:1.766 points.

[0127] Example 2 Compounds A2, 2aa and 2ab

change

[0128] To a solution of 52 (0.5 g, 2.13 mmol) in THF (10 mL) was added LiAlH4 (161.35 mg, 4.25 mmol) at 0 °C. The mixture was stirred at 0 °C for 0.5 h and then cooled to 0 °C. Water (0.22 mL) was added dropwise to the mixture at 0 °C. The mixture was stirred for 5 min. 15% NaOH (0.0.22 mL) was added to the mixture, which was at 0 °C, and the mixture was stirred for 20 min. Water (0.66 mL) was added dropwise to the mixture at 0 °C, and the mixture was stirred for 5 min. The mixture was dried over Na2SO4 and concentrated to give the crude product. The crude product was triturated with EA (5 mL) for 30 min to give 53 (0.2 g, 45.41% yield) as a white solid.

[0129] To a solution of 53 (200 mg, 965.13 umol) and SOCl2 (229.64 mg, 1.93 mmol, 140.03 uL) in DCM (4 mL) was added at 20°C. The mixture was stirred at 20°C for 2 h and then concentrated under reduced pressure to give the crude product. The crude product was used directly in the next step without further purification. Compound 54 (150 mg, 68.87% yield) was obtained as a white solid.

[0130] To a solution of 54 (150 mg, 572.23 umol, HCl), N,6-Dimethyl-5-piperazin-1-yl-pyridine-2-carboxamide (185.92 mg, 686.68 umol, HCl), and NaBr (117.75 mg, 1.14 mmol, 36.80 uL) in MeCN (1 mL) was added DIEA (443.73 mg, 3.43 mmol, 598.02 uL) at 20° C. The mixture was stirred at 80° C. for 2 h. The mixture was filtered and the cake was collected. The filtered cake was separated by SFC to give two products. Compounds 2aa (20.2 mg, 8.34% yield) and 2ab (25.4 mg, 10.48% yield) were obtained as white solids. The absolute configurations of 2aa and 2ab remain to be determined. The relative configurations are shown above and the configurations are assigned arbitrarily.

[0131] SFC method: Column: ChiralPak IH, 250×30mm, 10um; Mobile phase: [0.1%NH3H2O ​​EtOH]; B%: 50%-50%, 12 min.

[0132] Compound 2aa: 1 H NMR(400MHz,DMSO-d6) δ 10.61(s,1H),8.41(q,J=4.8Hz,1H),7.79(d,J=8.3Hz,1H),7.47(d,J=8.4H z,1H),6.98-6.78(m,3H),4.48(dd,J=4.6,7.7Hz,1H),3.44(s,2H),2.93(br s,4H),2.80(d,J=4.9Hz,3H),2.52(br s,4H),2.48(s,3H),1.89-1.68(m,2H),0.98(t,J=7.4Hz,3H).

[0133] Compound 2ab: 1 H NMR(400MHz,DMSO-d6) δ 10.63(s,1H),8.43(q,J=4.7Hz,1H),7.80(d,J=8.3Hz,1H),7.48(d,J=8.3H z,1H),6.99-6.81(m,3H),4.50(dd,J=4.5,7.8Hz,1H),3.46(s,2H),2.95(br s,4H),2.81(d,J=4.9Hz,3H),2.58-2.53(m,4H),2.50(s,3H),1.91-1.69(m,2H),1.00(t,J=7.4Hz,3H).

[0134] Example 3 Compounds A3, 3aa and 3ab [ka] To 15 (20 g, 116.87 mmol) in AcOH (200 mL) was added Br2 (74.71 g, 467.49 mmol, 24.10 mL) at 25° C. The mixture was stirred at 55° C. for 12 h and then concentrated under reduced pressure to remove AcOH. The mixture was extracted with EA (3×40 mL). The combined organic layers were washed with brine (3×30 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was used in the next step without further purification. Compound 16 (24.5 g, 83.84% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 8.06-7.80(m,1H),7.22(d,J=9.3Hz,1H),3.95(s,3H).

[0135] To a solution of 16 (24.5 g, 97.99 mmol) in MeOH (500 mL) was added Zn (25.63 g, 391.97 mmol) in portions (0.5 grams at a time in a batch) at 25° C. The mixture was stirred at 25° C. for 2 hours. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The filter cake was quenched with 0.1 N HCl (1 g scale each time) and stirred at 25° C. for 1 hour. The mixture was basified to pH 9 with solid NaHCO3. The residue was purified by column chromatography (SiO2, PE:EA=20:1-5:1). Compound 17 (19.6 g, 90.90% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 6.80-6.73(m,1H),6.65(dd,J=1.3,8.8Hz,1H),4.96(s,2H),3.79(s,3H).

[0136] To 17 (10 g, 45.45 mmol) in DCM (300 mL) was added BBr3 (28.46 g, 113.62 mmol, 79.53 mL) at 25° C. The mixture was stirred at 25° C. for 12 h and then poured into NaHCO3 (100 mL). The mixture was stirred at 0° C. for 0.5 h. The mixture was extracted with dichloromethane (3×50 mL). The combined organic layers were washed with brine (3×50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, PE:EA=20:1-5:1). Compound 18 (8.3 g, 88.65% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 9.74(br s,1H),6.63(dd,J=7.6,8.7Hz,1H),6.50-6.45(m,1H),4.72(br s,2H).

[0137] To a solution of 18 (10.88 g, 47.33 mmol) in H2O (120 mL) and EA (120 mL) was added NaHCO3 (2.92 g, 34.71 mmol, 1.35 mL) and 2-amino-4-bromo-3-fluoro-phenol (6.5 g, 31.55 mmol) at 25 °C. The mixture was stirred at 25 °C for 12 h and then concentrated under reduced pressure to give a residue. To the residue in DMF (120 mL) was added K2CO3 (4.36 g, 31.55 mmol) at 25 °C. The mixture was stirred at 25 °C for 12 h. The mixture was poured into ice water (360 mL) and then filtered. The filter cake was dried under high vacuum to give the product. The residue was used directly in the next step without further purification. Compound 19 (8.4 g, 97.13% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 11.05(br s,1H),7.20(dd,J=7.5,8.6Hz,1H),6.83(dd,J=1.5,8.8Hz,1H),4.58(dd,J=4.6,7.8Hz,1H),1.97-1.64(m,2H),0.98(t,J=7.4Hz,3H).

[0138] A mixture of 19 (8.79 g, 27.36 mmol) 6-bromo-2-ethyl-5-fluoro-4H-1,4-benzoxazin-3-one (5 g, 18.24 mmol) and [2-(2-aminophenyl)phenyl]-chloro-palladium;dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane (1.44 g, 1.82 mmol) in dioxane (100 mL) was degassed and purged with N2 (3 times). The mixture was stirred at 80 °C under N2 atmosphere for 12 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, PE:EA=50:1-1:1). Compound 20 (3.7 g, 90.06% yield) was obtained as a white solid. 1H NMR(400MHz,DMSO-d6) δ 10.83(s,1H),6.97(t,J=8.1Hz,1H),6.80(d,J=8.5Hz,1H),5.18(t,J=5.7Hz,1H),4.52 (dd,J=4.6,7.9Hz,1H),4.45(d,J=5.7Hz,2H),1.91-1.63(m,2H),0.98(t,J=7.4Hz,3H).

[0139] A mixture of 20 (6.3 g, 27.97 mmol) and SOCl2 (6.66 g, 55.95 mmol, 4.06 mL) in DCM (120 mL) was degassed and purged with N2 (3 times). The mixture was stirred under N2 atmosphere at 25 °C for 2 h. The mixture was filtered and the filter cake was concentrated under reduced pressure to give a residue. The residue was used directly in the next step without further purification. Compound 21 (6.5 g, 95.36% yield) was obtained as a white solid.

[0140] A mixture of 21 (3.10 g, 12.74 mmol), 6-fluoro-N-methyl-5-piperazin-1-yl-pyridine-2-carboxamide (3.5 g, 12.74 mmol, HCl), DIEA (9.88 g, 76.44 mmol, 13.31 mL), and NaBr (3.93 g, 38.22 mmol, 1.23 mL) in CH3CN (100 mL) was degassed and purged with N2 (3 times). The mixture was stirred under N2 atmosphere at 25 °C for 2 h. The mixture was filtered and the filter cake was concentrated under reduced pressure to give a residue that was separated by SFC and concentrated to give two products (Rt1 = 1.518 min, Rt2 = 1.747 min). The residue was purified by preparative HPLC (FA conditions). Compounds 3aa (0.97 g, 17.09% yield) and 3ab (1.7 g, 29.95% yield) were obtained as white solids. The absolute configurations of 3aa and 3ab remain to be determined. The relative configurations are shown above and the configurations are arbitrarily assigned.

[0141] Fractional HPLC method: Column: ChiralPak IH, 250×30 mm, 10 μm; Mobile phase: [0.1% NH₃·H₂O EtOH]; B%: 50% - 50%, 12 minutes. SFC method: Column: ChiralPak IH, 250×30 mm, 10 μm; Mobile phase: [0.1% NH₃·H₂O EtOH]; B%: 50% - 50%, 12 minutes

[0142] Compound 3aa: 1 H NMR (400 MHz, DMSO-d₆) δ 1.00 (t, J = 7.38 Hz, 3H) 1.68 - 1.93 (m, 2H) 2.55 (br s, 4H) 2.77 (d, J = 4.75 Hz, 3H) 3.15 (br s, 4H) 3.54 (br s, 2H) 4.55 (dd, J = 7.69, 4.57 Hz, 1H) 6.82 (d, J = 8.38 Hz, 1H) 6.95 (t, J = 7.94 Hz, 1H) 7.55 (dd, J = 10.51, 8.13 Hz, 1H) 7.84 (d, J = 7.88 Hz, 1H) 8.40 (q, J = 4.38 Hz, 1H) 10.84 (s, 1H).

[0143] Compound 3ab: 1 H NMR (400 MHz, DMSO-d₆) δ 0.99 (t, J = 7.38 Hz, 3H) 1.67 - 1.92 (m, 2H) 2.54 (br d, J = 4.25 Hz, 4H) 2.76 (d, J = 4.88 Hz, 3H) 3.14 (br s, 4H) 3.53 (br s, 2H) 4.55 (dd, J = 7.69, 4.57 Hz, 1H) 6.81 (d, J = 8.38 Hz, 1H) 6.90 - 6.98 (m, 1H) 7.54 (dd, J = 10.57, 8.19 Hz, 1H) 7.72 - 8.04 (m, 1H) 8.39 (q, J = 4.42 Hz, 1H) 10.83 (s, 1H).

[0144] Example 4 Compound A4

Chemical Structure

[0145] A mixture of 63B (1 g, 2.87 mmol) and K2CO3 (593.99 mg, 4.30 mmol) in NMP (20 mL) was degassed and purged with N2 (3 times). The mixture was stirred under N2 atmosphere at 80 °C for 2 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was used directly in the next step without purification. Compound 64 (680 mg, 88.52% yield) was obtained as a white solid.

[0146] To a mixture of [dibutyl(propyl)stannyl]methanol (171.79 mg, 559.48 umol) and 64 (100 mg, 372.99 umol) in dioxane (6 mL) was added XPhos-Pd-G2 (29.35 mg, 37.30 umol) at 25°C. The mixture was degassed and purged with N2 (3 times). The mixture was stirred at 80°C under N2 atmosphere for 12 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, PE:EA=50:1-2:1). Compound 65 (98 mg, 97.83% yield) was obtained as a white solid.

[0147] To a solution of 65 (98 mg, 456.13 umol) in DCM (5 mL) was added SOCl2 (108.53 mg, 912.26 umol, 66.18 uL) at 25°C. The mixture was stirred at 25°C for 2 h. The mixture was filtered and the filter cake was concentrated under reduced pressure to give a residue. The residue was used directly in the next step without purification. Compound 66 (95 mg, 98.4% yield) was obtained as a white solid.

[0148] To a mixture of N-methyl-5-piperazin-1-yl-pyridine-2-carboxamide (111.21 mg, 433.17 umol, HCl), 66 (80 mg, 336.58 umol) in ACN (2 mL) was added NaBr (103.90 mg, 1.01 mmol, 32.47 uL) and DIEA (261.01 mg, 2.02 mmol, 351.76 uL) at 25 °C. The mixture was degassed and purged with N2 (3 times). The mixture was stirred at 80 °C under N2 atmosphere for 2 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (FA conditions). Compound A4 (92 mg, 55.54% yield, 95.0% purity, FA) was obtained as a yellow solid. Preparative HPLC method: Column: Phenomenex C18 75×30 mm×3 um; Mobile phase: [water (FA)-ACN]; B%: 20%-45%, 8 min. 1H NMR(400MHz,DMSO-d6) δ 11.03(s,1H),8.41(br d,J=4.8Hz,1H),8.28(br s,1H),8.13(s,1H),7.85(br d,J=8.8Hz,1H),7.41(br d,J=7.6Hz,1H),7.10-6.86(m,3H),4.45-3.72(m,2H),3.28-2.92(m,4H),2.78(d,J=4.8Hz,3H) ,2.55-2.50(m,4H),2.49-2.45(m,2H),2.28-2.13(m,2H),1.99-1.85(m,1H),1.85-1.71(m,1H).

[0149] Example 5 Compound A5 [ka] To a mixture of methyl 1-hydroxycyclopropanecarboxylate (791.71 mg, 6.82 mmol) in THF (20 mL) was added NaH (363.61 mg, 9.09 mmol, 60% purity) at 0° C. The mixture was stirred at 25° C. for 15 min. Compound 62 (1 g, 4.55 mmol, 558.66 uL) was added to the mixture at 25° C. The mixture was degassed and purged with Ar (3 times). The mixture was stirred under Ar atmosphere at 25° C. for 12 h. The mixture was poured into NH4Cl and then filtered. The filter cake was concentrated under reduced pressure to give a residue. The residue was used directly in the next step without purification. Compound 68 (0.9 g, 62.64% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 1.34-1.50(m,2H) 1.56-1.70(m,2H) 3.66(s,3H) 7.22-7.38(m,1H) 7.74-7.90(m,1H) 8.05-8.21(m,1H).

[0150] A solution of 68 (810 mg, 2.56 mmol) and Fe (1.43 g, 25.62 mmol) in HOAc (18 mL) was degassed and purged with N2 (3 times). The mixture was stirred at 60 °C under N2 atmosphere for 3 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was used directly in the next step without purification. Compound 69 (580 mg, 89.08% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 1.15-1.21(m,2H) 1.21-1.29(m,2H) 3.33(s,1H) 6.84(d,J=8.25Hz,1H) 7.01-7.14(m,1H) 10.87(s,1H).

[0151] To a solution of tributylstannylmethanol (947.79 mg, 2.95 mmol) and 69 (500 mg, 1.97 mmol) in dioxane (10 mL) was added XPhos-Pd-G2 (154.83 mg, 196.79 umol) at 25° C. The mixture was degassed and purged with N2 (3 times). The mixture was stirred at 80° C. under N2 atmosphere for 12 h. The mixture was filtered and the filter cake was concentrated under reduced pressure to give a residue. The residue was used directly in the next step without purification. Compound 70 (180 mg, 44.57% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 1.10-1.18(m,2H) 1.19-1.26(m,2H) 4.39(d,J=5.75Hz,2H) 5.14(t,J=5.69Hz,1H) 6.77-6.96(m,3H) 10.74(s,1H).

[0152] To a solution of 70 (100 mg, 487.31 umol) in DCM (2 mL) was added SOCl2 (115.95 mg, 974.61 umol, 70.70 uL) at 0°C. The mixture was stirred at 20°C for 2 h. The mixture was filtered and the filter cake was concentrated under reduced pressure to give a residue. The residue was used directly in the next step without purification. Compound 71 (100 mg, 91.75% yield) was obtained as a white solid.

[0153] To a mixture of N-methyl-5-piperazin-1-yl-pyridine-2-carboxamide (154.96 mg, 603.61 umol, HCl) and 71 (90 mg, 402.41 umol) in ACN (1.8 mL) was added DIEA (312.05 mg, 2.41 mmol, 420.55 uL) and NaBr (124.22 mg, 1.21 mmol, 38.82 uL) at 25° C. The mixture was degassed and purged with N2 (3 times). The mixture was stirred at 80° C. under N2 atmosphere for 2 h. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (neutral conditions). Compound A4 (44.4 mg, 27.08% yield) was obtained as a yellow solid. Preparative HPLC method: Column: Waters Xbridge BEH C18 100 x 30 mm x 10 um; Mobile phase: [Water (NH4HCO3)-ACN]; B%: 25%-55%, 8 minutes. 1 H NMR(400MHz,DMSO-d6) δ 1.13-1.19(m,2H) 1.20-1.26(m,2H) 2.51(br s,4H) 2.78(d,J=4.88Hz,3H) 3.32-3.34(m,4H) 3.44(s,2H) 6.80-6.88(m,2H) 6.92(d,J=1.63Hz,1H) 7.38(dd,J=8.82,2.94Hz,1H) 7.77(br d,J=4.13Hz,1H) 8.25(d,J=2.75Hz,1H) 8.32-8.43(m,1H) 10.72(s,1H).

[0154] Example 6 Compound A6 [ka] To a solution of 1 (1 g, 4.55 mmol) and ethyl 1-hydroxycyclopropanecarboxylate (887.34 mg, 6.82 mmol) in THF (20 mL) was added NaH (363.64 mg, 9.09 mmol, 60% purity) under N2 at 0 °C. The mixture was stirred at 20 °C for 12 h. The mixture was poured into aqueous NH4Cl (20 mL) at 0 °C and then extracted with EA (3 × 20 mL). The combined organic phase was washed with brine (20 mL), dried over Na2SO4 and concentrated to give the crude product. The residue was purified by column chromatography (SiO2, PE:EA = 50:1-3:1). Compound 2 (1.2 g, 79.97% yield) was obtained as a yellow solid. 1 H NMR(400MHz,DMSO-d6) δ 8.16(d,J=2.4Hz,1H),7.83(dd,J=2.5,9.0Hz,1H),7.31(d,J=9.0Hz,1H),4.14 (q,J=7.1Hz,2H),1.66-1.58(m,2H),1.48-1.39(m,2H),1.13(t,J=7.1Hz,3H).

[0155] A mixture of 2 (1.2 g, 3.63 mmol), Fe (2.03 g, 36.35 mmol) in AcOH (20 mL) was degassed and purged with N2 (3 times). The mixture was stirred at 60 °C under N2 atmosphere for 3 h. The mixture was filtered and the filtrate was concentrated to give the crude product. The residue was purified by column chromatography (SiO2, PE:EA = 50:1-1:1). Compound 3 (530 mg, yield 57.39%) was obtained as a yellow solid. 1 H NMR(400MHz,DMSO-d6) δ 10.87(br s,1H),7.11-7.02(m,2H),6.85(d,J=8.5Hz,1H),3.32(s,18H),1.29-1.22(m,2H),1.21-1.16(m,2H).

[0156] To a solution of tributylstannylmethanol (1.00 g, 3.13 mmol) and XPhos-Pd-G2 (164.12 mg, 208.60 umol) in dioxane (10 mL) was added 3 (530 mg, 2.09 mmol) at 25° C. The mixture was stirred at 80° C. for 12 h. The mixture was filtered and the filtrate was concentrated to give the crude product. The residue was purified by column chromatography (SiO2, PE:EA=3:1-2:1). Compound 4 (390 mg, 91.11% yield) was obtained as a white solid.

[0157] A solution of 4 (390 mg, 1.90 mmol) and SOCl2 (452.20 mg, 3.80 mmol, 275.73 uL) in DCM (5 mL) was stirred at 25 °C for 2 h. The mixture was filtered and the filtrate was concentrated to give the crude product. The crude product was used directly in the next step without further purification. Compound 5 (300 mg, 70.58% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 10.94-10.79(m,1H),7.11-6.91(m,2H),6.86(d,J=7.9Hz,1H),4.82-4.53(m,2H),1.35-1.05(m,4H).

[0158] To a solution of N,6-dimethyl-5-piperazin-1-yl-pyridine-2-carboxamide (80 mg, 341.45 umol) and DIEA (173.36 mg, 1.34 mmol, 233.64 uL) in CH3CN (1 mL) was added 5 (50 mg, 223.56 umol) and NaBr (69.01 mg, 670.68 umol, 21.57 uL) at 25°C. The mixture was stirred at 80°C for 12 h. The mixture was filtered and the filtrate was concentrated to give the crude product. The residue was purified by preparative HPLC (neutral condition). Compound A6 (58.1 mg, 61.66% yield) was obtained as a white solid. Preparative HPLC method: Column: Waters Xbridge BEH C18 100 x 30 mm x 10 um; Mobile phase: [Water (NH4HCO3)-ACN]; B%: 35%-65%, 8 minutes 1H NMR(400MHz,DMSO-d6) δ 10.87-10.53(m,1H),8.47-8.37(m,1H),7.79(d,J=8.3Hz,1H),7.47(d,J=8.3Hz,1H),6.92(d,J=1.8Hz,1H), 6.89-6.80(m,2H),3.45(s,2H),3.01-2.73(m,7H),2.68-2.50(m,7H),1.26-1.20(m,2H),1.19-1.12(m,2H).

[0159] Example 7 Compound A7 [ka] To a solution of 5 (80 mg, 335.77 umol) and DIEA (260.37 mg, 2.01 mmol, 350.90 uL) in CH3CN (1.6 mL) was added 6-(chloromethyl)spiro[4H-1,4-benzoxazine-2,1'-cyclopropane]-3-one (75.10 mg, 335.77 umol) and NaBr (103.64 mg, 1.01 mmol, 32.39 uL). The mixture was stirred at 80°C for 12 h. The mixture was filtered and the filtrate was concentrated to give the crude product. The residue was purified by preparative HPLC (neutral condition). Compound A7 (67.5 mg, 47.70% yield) was obtained as a white solid. Preparative HPLC method: Column: Waters Xbridge BEH C18 100 x 30 mm x 10 um; Mobile phase: [Water (NH4HCO3)-ACN]; B%: 35%-65%, 8 minutes. 1 H NMR(400MHz,DMSO-d6) δ 10.81-10.61(m,1H),8.39(q,J=4.5Hz,1H),7.84(dd,J=1.1,8.0Hz,1H),7.55(dd,J=8.2,10.6Hz,1H),6.96-6.75(m,3H),3.44(s,2H),3.15(br d,J=4.5Hz,4H),2.76(d,J=4.8Hz,3H),1.27-1.20(m,2H),1.19-1.11(m,2H).

[0160] Example 8 Compounds A8 and A9 [ka] To a solution of 11 (1 g, 6.29 mmol, 666.67 uL) and methyl 1-hydroxycyclopropanecarboxylate (696.69 mg, 6.00 mmol) in THF (20 mL) was added NaH (342.86 mg, 8.57 mmol, 60% purity) under N2 at 0 °C. The mixture was stirred at 20 °C for 12 h. The mixture was poured into aqueous NH4Cl (50 mL) at 0 °C. The mixture was extracted with EA (3 x 10 mL). The combined organic phase was washed with brine (20 mL), dried over Na2SO4 and concentrated to give the crude product. The residue was purified by column chromatography (SiO2, PE:EA = 50:1-1:50). Compound 12 (1 g, 68.57% yield) was obtained as a yellow solid. 1 H NMR(400MHz,DMSO-d6) δ 7.63(dt,J=6.5,8.6Hz,1H),7.29-7.15(m,2H),3.68(s,3H),1.67-1.60(m,2H),1.48-1.40(m,2H).

[0161] To a solution of 12 (1 g, 3.92 mmol) in H2SO4 (10 mL) was added NBS (697.43 mg, 3.92 mmol) under N2 at 0 °C. The mixture was stirred at 25 °C for 12 h. The mixture was poured into ice water (20 mL) at 0 °C. The mixture was extracted with EA (3 x 20 mL). The combined organic phase was washed with brine (20 mL), dried over Na2SO4 and concentrated to give the crude product. The residue was purified by column chromatography (SiO2, PE:EA = 50:1-4:1). Compound 13 (0.7 g, 53.47% yield) was obtained as a yellow solid. 1 H NMR(400MHz,DMSO-d6) δ 7.91(dd,J=7.9,9.3Hz,1H),7.21(dd,J=1.7,9.3Hz,1H),3.67(s,3H),1.65-1.59(m,2H),1.47-1.42(m,2H).

[0162] To a solution of 13 (700 mg, 2.10 mmol) in AcOH (10 mL) was added Fe (1.17 g, 20.95 mmol) under N2 at 25°C. The mixture was stirred at 60°C for 3 h. The mixture was poured into aqueous NH4Cl (20 mL) at 0°C. The mixture was extracted with EA (3 x 20 mL). The combined organic phases were washed with brine (20 mL), dried over Na2SO4 and concentrated to give the crude product. The residue was purified by column chromatography (SiO2, PE:EA = 50:1-1:50). Compound 8 (560 mg, 98.24% yield) was obtained as a yellow solid. 1 H NMR(400MHz,DMSO-d6) δ 11.38-11.04(m,1H),7.22(dd,J=7.5,8.6Hz,1H),6.75(dd,J=1.3,8.8Hz,1H),1.32-1.26(m,2H),1.26-1.19(m,2H).

[0163] A mixture of 8 (560 mg, 2.06 mmol), tributylstannylmethanol (991.33 mg, 3.09 mmol) in dioxane (10 mL) was degassed and purged with N2 (3 times), then [2-(2-aminophenyl)phenyl]-chloro-palladium;dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane (161.95 mg, 205.83 umol) was added to the mixture under N2. The mixture was stirred at 80° C. for 12 h under N2 atmosphere. The mixture was filtered and concentrated to give the crude product. The residue was purified by column chromatography (SiO2, PE:EA=50:1-3:1). Compound 9 (320 mg, 69.65% yield) was obtained as a white solid. 1 H NMR(400MHz,DMSO-d6) δ 7.80(br d,J=0.8Hz,1H),6.99(t,J=8.2Hz,1H),6.68(dd,J=0.9,8.4Hz,1H),4.72(s,2H),1.51-1.44(m,2H),1.30-1.24(m,2H).

[0164] A mixture of 9 (320 mg, 1.43 mmol) in DCM (0.5 mL) was degassed and purged with N2 (3 times), then SOCl2 (341.13 mg, 2.87 mmol, 208.01 uL) was added under N2. The mixture was stirred at 25 °C under N2 atmosphere for 2 h. The mixture was concentrated to give a residue. The residue was used directly in the next step without further purification. Compound 14 (250 mg, 72.16% yield) was obtained as a white solid.

[0165] To a solution of N,6-dimethyl-5-piperazin-1-yl-pyridine-2-carboxamide (89.64 mg, 331.06 umol, HCl) and DIEA (256.72 mg, 1.99 mmol, 345.98 uL) in CH3CN (0.5 mL) was added 14 (80 mg, 331.06 umol) and NaBr (102.19 mg, 993.19 umol, 31.93 uL) at 25°C. The mixture was stirred at 80°C for 12 h. The mixture was filtered and the filtrate was concentrated to give the crude product. The residue was purified by preparative HPLC to give A8 (97.6 mg, 60.11% yield) as a white solid. Column: Phenomenex Luna C18 75×30mm×3um; Mobile phase: [water (FA)-ACN]; B%: 5%-40%, 8min. 1 H NMR(400MHz,DMSO-d6) δ 10.97(s,1H),8.46-8.35(m,1H),8.15(s,1H),7.78(d,J=8.3Hz,1H),7.46(d,J =8.3Hz,1H),6.95(t,J=7.9Hz,1H),6.73(d,J=8.4Hz,1H),3.55(s,2H),2.92(br s,4H),2.79(d,J=4.8Hz,3H),2.57(br s,4H),2.48(s,3H),1.31-1.24(m,2H),1.23-1.17(m,2H).

[0166] To a solution of 6-fluoro-N-methyl-5-piperazin-1-yl-pyridine-2-carboxamide (90.95 mg, 331.06 umol, HCl) and DIEA (256.72 mg, 1.99 mmol, 345.98 uL) in CH3CN (0.5 mL) was added 10 (80 mg, 331.06 umol) and NaBr (102.19 mg, 993.19 umol, 31.93 uL) at 25°C. The mixture was stirred at 80°C for 12 hours. The mixture was filtered and the filtrate was concentrated to give the crude product. The residue was purified by preparative HPLC (or neutral conditions). Compound A9 (72.6 mg, 148.18 umol, 44.76% yield, 99.9% purity, FA salt) was obtained as a white solid. Column: Phenomenex Luna C18 75×30mm×3um; Mobile phase: [water (FA)-ACN]; B%: 5%-40%, 8 min, 1 H NMR(400MHz,DMSO-d6) δ 10.97(s,1H),8.39(q,J=4.4Hz,1H),7.83(d,J=8.1Hz,1H),7.54(dd,J=8.3,1 0.4Hz,1H),6.95(t,J=8.0Hz,1H),6.73(d,J=8.4Hz,1H),3.54(s,2H),3.14(br s,4H),2.76(d,J=4.9Hz,3H),2.55(br s,4H),1.31-1.24(m,2H),1.23-1.16(m,2H).

[0167] Example 9 Additional Compounds Additional compounds of formula (I) can be prepared using similar materials and methods described herein, such as those described herein. [ka] [ka] [ka] [ka] [ka] (including stereoisomers / pharma- ceutically acceptable salts of any of the foregoing).

[0168] Example A PARP assay FP binding assay (PARP1, PARP2) PARP1 and PARP2 proteins and PARPi-FL were purchased from BPS Bioscience. Assay buffer was 50 mM Tris (pH 8.0), 0.001% Triton X-100, 10 mM MgCl2, 150 mM NaCl. Compounds were diluted to apical concentrations in 384PP-plates and transferred sequentially to Optiplate-384F plates. Compounds (20 nL) or DMSO were added to the assay plate, followed by 10 uL of 40 nM PARP1 or PARP2 (diluted using assay buffer). Assay plates were centrifuged at 1000 rpm for 1 min and then incubated at room temperature for 30 min. 6 nM PARPi-FL (diluted using assay buffer) (10 uL) was added to the plate (final concentrations of PARP1 and PARP2 were 20 nM and PARPi-FL was 3 nM). After centrifugation at 1000 rpm for 1 minute, the assay plate was incubated at room temperature for 4 hours. The plate was read using Envision with an excitation filter. Data analysis was performed by calculating the percentage inhibition using the mP values ​​using the following equation: Inhibition (%) = (1-mpC-mpL) / mpH-mpL x 100%.

[0169] Proliferation assay in DLD-1 wt and DLD-1 BRCA2 (PARP inhibitor) Culture DLD-1-wt and DLD-1 mutant cells in RPMI 1640 + 10% FBS + 1% PS. Allow the cells to settle in culture medium for 2-3 days. Resuspend the cells in culture medium (density 2-3 × 10 6) and 40 μL of cell suspension (50 cells / well for DLD-1 wt and 50 cells / well for DLD-1 BRCA(- / -). Cover the plate and spin at 1000 rpm for 1 minute at room temperature and then transfer. Place the plate in a 5% CO2 incubator at 37°C overnight. Test compounds are dissolved in 10 mM DMSO stock solutions and then 40 uL of the stock solution is diluted to 384 Transfer to PP plate. Using a TECAN (EVO200) liquid handler, perform a 10-point dilution by transferring 10 uL of compound to 30 μL of DMSO. Spin the plate at 1000 rpm for 1 minute at room temperature, then shake on a plate shaker for 2 minutes. Using a liquid handler, transfer 40 nL of diluted compound to the cell plate. After 7 days of incubation, perform a CTG detection assay. The CTG detection assay is performed by removing the plate from the incubator, then equilibrating at room temperature for 15 minutes. Thaw CellTiter Glo reagent and equilibrate at room temperature. Add CellTiter-Glo reagent (30 μL) to each well, place the plate at room temperature for 30 minutes, and then read on EnVision. Inhibitory activity is calculated using the formula: % Inhibition = 100 x (LumHC-LumSample) / (LumHC-LumLC).

[0170] The results of the cell-based assay are provided in Table 1. In Table 1, "A" denotes an IC of <0.1 μM 50 "B" indicates IC of ≥ 0.1 μM and < 1.0 μM 50 "C" indicates IC ≥ 1.0 μM 50 As shown by the results in Table 1, the compounds of formula (I) (including pharma- ceutically acceptable salts thereof) are effective PARP1 inhibitors. [Table 2]

[0171] The results of the biochemical assays are provided in Table 2. In Table 2, "A" denotes an IC of <0.005 μM. 50 "B" indicates IC of ≥ 0.005 μM and < 0.01 μM.50 "C" indicates IC of ≥ 0.01 μM 50 As shown by the results in Table 2, the compounds of formula (I) (including pharma- ceutically acceptable salts thereof) are effective PARP1 inhibitors. [Table 3]

[0172] Although the foregoing has been described in some detail by way of illustration and example for purposes of clarity and understanding, it will be appreciated by those skilled in the art that numerous and various modifications may be made without departing from the spirit of the present disclosure. It is therefore to be clearly understood that the forms disclosed herein are illustrative only and are not intended to limit the scope of the present disclosure, but are intended to encompass all modifications and alternatives which come within the true scope and spirit of the present disclosure.

Claims

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof, 【Chemistry 1】 During the ceremony, Y １ However, O, CH ２ , or CR Ｙ１ R Ｙ２ And R Ｙ１ and R Ｙ２ Each of these independently comprises deuterium, halogen, or unsubstituted C. １－４ It is alkyl, Ring A is selected from the group consisting of pyrrole, thiophene, pyridine, and phenyl, and the pyrrole, the thiophene, the pyridine, or the phenyl is optionally deuterium, halogen, unsubstituted C １－４ alkyl, unsubstituted C １－４ alkoxy, unsubstituted C １－４ haloalkyl, and unsubstituted C １－４ substituted with one or more substituents independently selected from haloalkoxy, respectively, Ring B is selected from the group consisting of a 6-membered monocyclic nitrogen-containing heterocycline, a 7-membered bicyclic nitrogen-containing heterocycline, and an 8-membered bicyclic nitrogen-containing heterocycline. Ring C is selected from the group consisting of pyrrole, thiophene, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, and phenyl. R １ａ However, hydrogen, deuterium, and unsubstituted carbon ２－４ Alkyl, substituted C １－４ Alkyl, unsubstituted C ２－４ Alkenyl, unsubstituted C １－４ Haloalkyl, unsubstituted C １－４ Hydroxyalkyl, unsubstituted monocyclic C ３－６ Cycloalkyl, substituted monocyclic C ３－６ Cycloalkyl, unsubstituted bicyclic C ５－８ Cycloalkyl, substituted bicyclic C ５－８ Cycloalkyl, unsubstituted monocyclic C ３－６ Cycloalkyl (unsubstituted C １－４ Alkyl), Substituted monocyclic C ３－６ Cycloalkyl (unsubstituted C １－４ Alkyl), unsubstituted monocyclic C ３－６ Cycloalkyl (unsubstituted C ２－４ Alkenyl), and substituted monocyclic C ３－６ Cycloalkyl (unsubstituted C ２－４ Selected from the group consisting of alkenyls, the substituted C １－４ The alkyl group is substituted with one or more deuterium atoms, and the monocyclic C ３－６ Cycloalkyl, the substituted bicyclic C ５－８ Cycloalkyl, the substituted monocyclic C ３－６ Cycloalkyl (unsubstituted C １－４ Alkyl), and the substituted monocyclic C ３－６ Cycloalkyl (unsubstituted C ２－４ The alkenyl is independently substituted by one or more substituents independently selected from deuterium and halogens. R １ｂ However, hydrogen, deuterium, and unsubstituted carbon １－４ Alkyl or unsubstituted C １－４ It is a haloalkyl, or R １ａ and R １ｂ However, R １ａ and R １ｂ Together with the bonded carbon atom, it forms an unsubstituted or substituted monocyclic 3-4 membered cycloalkyl or an unsubstituted or substituted monocyclic 4-5 membered heterocycline, and the substituted monocyclic 3-4 membered cycloalkyl and the substituted 4-5 membered heterocycline are deuterium, halogen, and unsubstituted C １－３ Alkyl and unsubstituted C １－３ Each is independently substituted with one or more substituents independently selected from the haloalkyl group. However, R １ｂ If R is hydrogen, １ａ However, deuterium, unsubstituted C ２－４ Alkyl, substituted C １－４ Alkyl unsubstituted C ２－４ Alkenyl, unsubstituted C １－４ Haloalkyl, unsubstituted C １－４ Hydroxyalkyl, unsubstituted monocyclic C ３－６ Cycloalkyl, substituted monocyclic C ３－６ Cycloalkyl, unsubstituted bicyclic C ５－８ Cycloalkyl, substituted bicyclic C ５－８ Cycloalkyl, unsubstituted monocyclic C ３－６ Cycloalkyl (unsubstituted C １－４ Alkyl), Substituted monocyclic C ３－６ Cycloalkyl (unsubstituted C １－４ Alkyl), unsubstituted monocyclic C ３－６ Cycloalkyl (unsubstituted C ２－４ Alkenyl), and substituted monocyclic C ３－６ Cycloalkyl (unsubstituted C ２－４ Selected from the group consisting of alkenyls, the substituted C １－４ The alkyl group is substituted with one or more deuterium atoms, and the monocyclic C ３－６ Cycloalkyl, the substituted bicyclic C ５－８ Cycloalkyl, the substituted monocyclic C ３－６ Cycloalkyl (unsubstituted C １－４ Alkyl), and the substituted monocyclic C ３－６ Cycloalkyl (unsubstituted C ２－４ The alkenyl is independently substituted by one or more substituents independently selected from deuterium and halogens, R ２ and R ３ Each of these independently contains hydrogen, deuterium, or unsubstituted C. １－４ It is alkyl, or R ２ and R ３ However, R ２ and R ３ Together with the bonded carbon atom, it forms an unsubstituted or substituted monocyclic C ３－６ Forming a cycloalkyl group, m is 0, 1, or 2, n is 0, 1, or 2, Each R ３ａ These independently produce deuterium, halogen, and unsubstituted C. １－４ Alkyl, unsubstituted C １－４ Haloalkyl, cyanosubstituted C １－４ Alkyl and unsubstituted monocyclic C ３－６ Selected from the group consisting of cycloalkyl groups, Each R ３ｂ is independently deuterium, halogen, unsubstituted C １－４ alkyl, deuterium-substituted C １－４ alkyl, unsubstituted C ２－４ alkenyl, unsubstituted C １－４ haloalkyl, unsubstituted monocyclic C ３－６ cycloalkyl, and unsubstituted monocyclic C ３－６ cycloalkyl (unsubstituted C １－４ alkyl), and is selected from the group consisting of R ４ However, -C(=O)NR ５ R ６ And, R ５ is hydrogen or unsubstituted C １－４ alkyl, and R ６ However, hydrogen, unsubstituted C １－４ Alkyl, substituted C １－４ Alkyl, unsubstituted monocyclic C ３－６ Cycloalkyl, unsubstituted bicyclic C ５－８ Cycloalkyl, unsubstituted monocyclic C ３－６ Cycloalkyl (unsubstituted C １－４ Alkyl, or unsubstituted bicyclic C ５－８ Cycloalkyl (unsubstituted C １－４ Alkyl) and the substituted C １－４ The alkyl group is substituted with one or more deuterium atoms, provided that the compound of formula (I) or a pharmaceutically acceptable salt thereof is: 【Chemistry 2-1】 【Chemistry 2-2】 【change】 A compound, or a pharmaceutically acceptable salt thereof, provided that it is not a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein ring A is thiophene, pyridine, or phenyl, and the thiophene, pyridine, or phenyl is optionally substituted with one or more substituents independently selected from deuterium, halogen, unsubstituted C1-4 alkyl, unsubstituted C1-4 alkoxy, unsubstituted C1-4 haloalkyl, and unsubstituted C1-4 haloalkoxy.

3. Ring A is 【Transformation 3】 Selected from, Ring A is optionally substituted with one or more substituents independently selected from deuterium, halogen, unsubstituted C1-4 alkyl, unsubstituted C1-4 alkoxy, unsubstituted C1-4 haloalkyl, and unsubstituted C1-4 haloalkoxy. * indicates a point in formula (I) where ring A is bonded to -NH-C(=O)-C(R 1a)(R 1b)-Y 1-, the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein ring B is a 6-membered monocyclic nitrogen-containing heterocycline, a 7-membered bicyclic nitrogen-containing heterocycline, or an 8-membered bicyclic nitrogen-containing heterocycline.

5. Ring B is 【Chemistry 4】 A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the above.

6. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1 and n is 0 or 1.

7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 3a is an unsubstituted C1-4 alkyl or an unsubstituted C1-4 haloalkyl.

8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein ring C is thiophene, thiazole, pyridine, pyridazine, pyrimidine, or phenyl.

9. Ring C is 【Transformation 5】 A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the above.

10. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 3b is deuterium, halogen, unsubstituted C1-4 alkyl, deuterium-substituted C1-4 alkyl, or unsubstituted C1-4 haloalkyl.

11. R5 is hydrogen, The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 6 is hydrogen, an unsubstituted C1-4 alkyl, a substituted C1-4 alkyl, an unsubstituted monocyclic C3-6 cycloalkyl, an unsubstituted bicyclic C5-8 cycloalkyl, an unsubstituted monocyclic C3-6 cycloalkyl (unsubstituted C1-4 alkyl), or an unsubstituted bicyclic C5-8 cycloalkyl (unsubstituted C1-4 alkyl).

12. (a) R 1a is hydrogen, unsubstituted or substituted C 2-4 alkyl, unsubstituted C 2-4 alkenyl, unsubstituted C 1-4 haloalkyl, unsubstituted C 1-4 hydroxyalkyl, unsubstituted or substituted monocyclic C 3-6 cycloalkyl, unsubstituted or substituted bicyclic C 5-8 cycloalkyl, unsubstituted or substituted monocyclic C 3-6 cycloalkyl (unsubstituted C 1-4 alkyl), or unsubstituted or substituted monocyclic C 3-6 cycloalkyl (unsubstituted C 2-4 alkenyl); and R1b is hydrogen, an unsubstituted C1-4 alkyl, or an unsubstituted C1-4 haloalkyl; or (b) The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R1a and R1b, together with the carbon atoms to which R1a and R1b are bonded, form an unsubstituted or substituted monocyclic 3-4 membered ring cycloalkyl or an unsubstituted or substituted monocyclic 4-5 membered ring heterocycline.

13. (a) R2 and R3 are each hydrogen or an unsubstituted C1-4 alkyl; or (b) The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R2 and R3, together with the carbon atom to which R2 and R3 are bonded, form an unsubstituted or substituted monocyclic C3-6 cycloalkyl group. 【Request Item 14】 【Chemistry 9-1】 【change】 【Chemistry 9-2】 【change】 【Chemistry 9-3】 【change】 【Chemistry 9-4】 【change】 【change】 【Chemistry 9-5】 【change】 【Chemistry 9-6】 【change】 【Chemistry 9-7】 【change】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the compounds and pharmaceutically acceptable salts thereof. 【Request Item 15】 【Chemistry 10-1】 【Chemistry 10-2】 【change】 【Chemistry 10-3】 【change】 [Chemistry 10-4] 【change】 【Transformation 10-5】 【change】 【Chemistry 10-6】 【change】 【Chemistry 10-7】 【change】 [Transformation 10-8] 【change】 【Chemistry 10-9】 【change】 【Chemistry 10-10】 【change】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the compounds and pharmaceutically acceptable salts thereof.

16. The compound is 【Chemistry 11】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

17. The compound is 【Chemistry 12】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

18. The compound is 【Chemistry 13】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

19. The compound is 【Chemistry 14】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

20. The compound is 【Chemistry 15】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

21. The compound is 【Chemistry 16】 The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

22. A pharmaceutical composition comprising a compound according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, or excipients, or a combination thereof.

23. A pharmaceutical composition according to claim 22 for treating cancer.

24. The pharmaceutical composition according to claim 23, wherein the cancer is selected from the group consisting of lung cancer, pancreatic cancer, colon cancer, myeloid leukemia, thyroid cancer, myelodysplastic syndrome (MDS), bladder cancer, epidermal cancer, melanoma, breast cancer, prostate cancer, head and neck cancer, ovarian cancer, brain cancer, mesenchymal cancer, sarcoma, teratoma, neuroblastoma, kidney cancer, liver cancer, non-Hodgkin lymphoma, multiple myeloma, and anaplastic thyroid carcinoma.

25. The pharmaceutical composition according to claim 23, wherein the cancer is selected from colorectal cancer, acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic myelomonocytic leukemia (CMML), squamous cell carcinoma of the head and neck, glioblastoma, fibrosarcoma, and rhabdomyosarcoma.

26. A pharmaceutical composition according to claim 22 for inhibiting PARP1.

27. ​​A method for producing a compound according to any one of claims 1 to 21 or a pharmaceutically acceptable salt thereof, comprising one or more steps described in the scheme below. 【Chemistry 17】

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