Ikaros zinc finger family degraders and uses thereof

Abstract

This disclosure generally relates to compounds that bind to and act as degraders of IKZF family zinc finger (IKZF) proteins, such as IKZF2 (Helios) and / or IKZF4 (Eos) . This disclosure further relates to the use of such compounds in the preparation of pharmaceuticals for treating diseases and / or conditions (including cancer) by binding to and degrading IKZF proteins, such as IKZF2 and / or IKZF4 .

Description

IKAROS Zinc Finger Degradants and Their Uses Cross-referencing of related applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 321,030, filed March 17, 2022, and U.S. Provisional Patent Application No. 63 / 386,605, filed December 8, 2022, pursuant to 35 USC § 119(e), the entire contents of which are hereby incorporated herein by reference for all purposes. This disclosure relates to compounds that bind to and act as degraders of IKZF family zinc finger (IKZF) proteins, such as IKZF2 (Helios) and / or IKZF4 (Eos) . This disclosure further relates to the use of these compounds for the treatment and / or prevention of diseases and / or conditions associated with one or more IKZF proteins (e.g., IKZF2 and / or IKZF4-related diseases or conditions), wherein reducing IKZF2 and / or IKZF4 protein levels can improve the disease or condition. sequence list This application contains a sequence list of electronically submitted files in .XML file format, the full text of which is hereby incorporated by reference. The .XML copy (created on February 21, 2023) is named 1423-TW-NP.xml and has a file size of 2,745 bytes. The IKAROS transcription factor family comprises five members: Ikaros (IKZF1), Helios (IKZF2), Aiolos (IKZF3), Eos (IKZF4), and Pegasus (IKZF5). Helios shares approximately 50% identity with Ikaros, Aiolos, and Eos, and binds to the same common DNA sites. When co-expressed in cells, these four IKZF proteins can heterodimerize with each other. Ikaros, Helios, and Aiolos are primarily expressed in hematopoietic cells, while Eos and Pegasus are more widely expressed in various tissues. Regulatory T cells (Tregs) are a subset of CD4+ T cells that maintain normal immune tolerance and homeostasis. Treg activity can also suppress antitumor immune responses. Helios is believed to be necessary for maintaining a stable Treg phenotype, particularly in the context of an inflammatory tumor microenvironment. Knockout of the Helios gene in Tregs has shown reduced Treg immunosuppressive activity and induced effector T cell phenotype. First-generation small-molecule Helios degraders have shown similar effects. Therefore, Helios has become a promising target in immuno-oncology. Furthermore, Helios degraders are expected to be used to treat chronic viral infections characterized by high levels of activated Tregs. There is still a need for Helios degraders that possess the desired selectivity, potency, metabolic stability, or reduction of harmful effects. This disclosure provides compounds that can be used as degraders of IKAROS family zinc finger (IKZF) protein 2 (IKZF2; Helios). This disclosure further relates to the use of these compounds in treating and / or preventing diseases and / or conditions by binding to and degrading IKZF2 protein. In one embodiment, a compound of formula (I) is provided herein. (I) or its pharmaceutically acceptable salt, wherein: R 1 System-H; R 2 -H, -F, or -Cl; R 21 -H, -F, or -Cl; R 3 -H, -F, or -Cl; R 4a and R 4b Each can be independently of -H, halogen, -OH, or C. 1-6 Alkyl; Cyclic A-series C 3-10 Cycloalkyl or heterocyclic groups; n-series 0, 1, 2, 3, or 4; each R 5 Independent halogens, =O, =CH 2. -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, -O-(R) 51 ), or -N(R 51 (R) 52 ); where R 5 Each of = CH 2. Alkyl, alkenyl, cycloalkyl, alkoxy, haloalkyl, haloalkoxy, heterocyclic, aryl, or heteroaryl groups may optionally be derived from one to four identical or different R groups. 5a Replace; Each R 5a Independent halogens, -CN, C 1-6 Alkyl, C 6-10 aryl, or -O(R) 51 ); where each R can be the same or different 51 and R 52 Independent phylogenetic systems - H, C 1-6 Alkyl, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl; R 6 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 1a (R) 1b ), -S(O)(NR 1a (R) 1b -C(O)R 1c -S(O) 2)R 1c 、or -C(O)OR 1d , where R 6 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 2a (R) 2b ), -S(O)(NR 2a (R) 2b -C(O)R 2c S(O) 2)R 2c 、or -C(O)OR 2d , where R 7 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 20 heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, =O, imine, -NO 2. -N 3. -CN, -OR 3a -C(O)-R 3a -C(O)OR 3a -C(O)-N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + ,-N(R 3a )C(O)-R 3b -N(R) 3a )C(O)OR 3b -N(R) 3a )C(O)N(R 3b (R) 3c ), -N(R 3a S(O) 2(R 3b -NR 3a S(O) 2N(R 3b (R) 3c -NR 3a S(O) 2O(R 3b -OC(O)R 3a -OC(O)OR 3a -OC(O)-N(R) 3a (R) 3b ), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R 3a (R) 3b ), -S(O)(NR 3a )R 3b -S(O)(NR) 3a )N(R 3b (R) 3c ),-SF 5. or -Si(R) 3a ) 3; where each Z 1 Z 2 、or Z 3 The alkyl, halogen, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups may each be optionally derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 halogenated, C 1-6 Alkoxy, C 1-6 halogenated alkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, =O, -NO 2. -CN, -N 3. -OR 3a -C(O)R 3a -C(O)OR 3a -C(O)N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + -N(R) 3a )-C(O)R 3b -N(R) 3a )C(O)O(R 3b ), -N(R 3a )C(O)N(R 3b (R) 3c ), -N(R 3a S(O) 2(R 3b ), -N(R 3a S(O) 2-N(R 3b (R) 3c ), -N(R 3a S(O) 2O(R 3b -OC(O)R 3a -OC(O)OR 3a -OC(O)-N(R) 3a (R) 3b ), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R 3a (R) 3b ), -S(O)(NR 3a )R 3b 、or -Si(R 3a ) 3; where Z 1a The alkyl, halogen, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups may each be optionally derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent C 1-9 Alkyl, C 1-8 halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 Cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, lateral group, -OH, -CN, -NO 2. -NH 2. -N 3. -SH, -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 2-6 alkenyl), -O(C) 2-6 alkynyl group), -O(C 3-15 cycloalkyl), -O (heterocyclic), -O (C 6-10 aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 2-6 alkenyl), -NH (C 2-6 ynyl group), -NH(C 3-15 cycloalkyl), -NH (heterocyclic), -NH (C 6-10 aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 1-8 (haloalkyl) 2. -N(C 2-6 alkenyl) 2. -N(C 2-6 (alkynyl group) 2. -N(C 3-15 cycloalkyl) 2. -N (heterocyclic group) 2. -N(C 6-10 Aryl) 2. -N (Heteroaryl) 2. -N(C 1-9 Alkyl)(C 1-8 Halogenated groups), -N(C) 1-9 Alkyl)(C 2-6 alkenyl), -N(C) 1-9 Alkyl)(C 2-6 alkynyl group), -N(C 1-9 Alkyl)(C 3-15 cycloalkyl), -N(C) 1-9 Alkyl (heterocyclic), -N(C) 1-9 Alkyl)(C 6-10 aryl), -N(C 1-9 Alkyl)(heteroaryl), -C(O)(C 1-9 Alkyl), -C(O)(C 1-8 Halogenated groups), -C(O)(C 2-6 alkenyl), -C(O)(C 2-6 ynyl group), -C(O)(C 3-15 cycloalkyl), -C(O)(heterocyclic), -C(O)(C 6-10 aryl), -C(O)(heteroaryl), -C(O)O(C 1-9 Alkyl), -C(O)O(C 1-8 Halogenated alkyl groups), -C(O)O(C 2-6 alkenyl), -C(O)O(C 2-6 alkynyl group), -C(O)O(C 3-15 cycloalkyl), -C(O)O (heterocyclic), -C(O)O (C 6-10 aryl), -C(O)O (heteroaryl), -C(O)NH 2. -C(O)NH(C) 1-9 Alkyl), -C(O)NH(C 1-8 Halogenated groups), -C(O)NH(C 2-6 alkenyl), -C(O)NH(C 2-6 ynyl group), -C(O)NH(C 3-15cycloalkyl), -C(O)NH (heterocyclic), -C(O)NH (C 6-10 aryl), -C(O)NH (heteroaryl), -C(O)N(C 1-9 alkyl) 2. -C(O)N(C 1-8 (haloalkyl) 2. -C(O)N(C 2-6 alkenyl) 2. -C(O)N(C 2-6 (alkynyl group) 2. -C(O)N(C 3-15 cycloalkyl) 2. -C(O)N (heterocyclic group) 2. -C(O)N(C 6-10 Aryl) 2. -C(O)N (Heteroaryl) 2. -NHC(O)(C 1-9 Alkyl), -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 2-6 alkenyl), -NHC(O)(C 2-6 ynyl group), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (C 6-10 aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 alkenyl), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (C 6-10 aryl), -NHC(O)O(heteroaryl), -NHC(O)NH(C 1-9 alkyl), -NHC(O)NH(C 1-8 Halogenated groups), -NHC(O)NH(C 2-6 alkenyl), -NHC(O)NH(C 2-6 ), -NHC(O)NH(C 3-15 cycloalkyl), -NHC(O)NH (heterocyclic), -NHC(O)NH (C 6-10 aryl), -NHC(O)NH (heteroaryl), -NHS(O)(C 1-9 alkyl), -N(C) 1-9 Alkyl)(S(O)(C) 1-9 alkyl), -S(C 1-9 alkyl), -S(C 1-8 Halogenated groups), -S(C 2-6 alkenyl), -S(C 2-6 alkynyl group), -S(C 3-15 cycloalkyl), -S (heterocyclic), -S (C 6-10 aryl), -S(heteroaryl), -S(O)N(C 1-9 alkyl) 2. -S(O)(C 1-9 Alkyl), -S(O)(C 1-8 Halogenated groups), -S(O)(C 2-6 alkenyl), -S(O)(C 2-6 ynyl group), -S(O)(C 3-15 cycloalkyl), -S(O)(heterocyclic), -S(O)(C 6-10 Aryl), -S(O) (heteroaryl), -S(O) 2(C 1-9 Alkyl groups, -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 2-6 alkenyl), -S(O) 2(C 2-6 Alkyne group), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(C 6-10 Aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups, -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2; where Z 1b The alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally have one to three carbon atoms. 1-9 Alkyl, C 1-8 Halogenated groups, halogens, -OH, -NH 2. -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 3-15 cycloalkyl), -O (heterocyclic), -O (aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 3-15 cycloalkyl), -NH (heterocyclic), -NH (aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 3-15 cycloalkyl) 2. -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (aryl), -NHC(O)O (heteroaryl), -NHC(O)NH(C 1-9 Alkyl groups), S(O) 2(C 1-9 Alkyl groups, -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups, -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2 Replacement; Each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c Independent phylogenetic systems - H, C 1-9 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Substitution; wherein, unless otherwise specified, the aryl groups of the compounds of formula (I) are C 6-10 Aryl; wherein, unless otherwise specified, each heteroaryl group of the compound of formula (I) is a 5- to 12-membered heteroaryl group having one to four heteroatoms of N, O, or S; wherein, unless otherwise specified, each heterocyclic group of the compound of formula (I) is a 3- to 20-membered heterocyclic group having one to four heteroatoms of N, O, or S. In some embodiments, this document provides pharmaceutical compositions comprising the compounds provided herein, or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable excipients or carriers. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the compounds provided herein, or pharmaceutically acceptable salts thereof, and pharmaceutically acceptable excipients or carriers. In some embodiments, the pharmaceutical composition provided herein further comprises one or more (e.g., one, two, three, four, one or two, one to three, or one to four) additional therapeutic agents or pharmaceutically acceptable salts thereof. In some embodiments, the pharmaceutical composition further comprises a therapeutically effective amount of one or more (e.g., one, two, three, four, one or two, one to three, or one to four) additional therapeutic agents or pharmaceutically acceptable salts thereof. In some embodiments, this disclosure provides a method for degrading the IKZF2 protein of a subject in need, comprising administering to the subject a therapeutically effective amount of a compound provided herein (e.g., a compound of formula (I), (Ia), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (IVb), (V), (Va), (VI), or (VIa)), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein. In some embodiments, this disclosure provides a method of treating a patient with an IKZF2 protein-mediated condition, comprising administering to the patient a therapeutically effective amount of a compound provided herein (e.g., a compound of formula (I), (Ia), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (IVb), (V), (Va), (VI), or (VIa)), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein. In some embodiments, this disclosure provides a method of treating a cancer patient, comprising administering to the cancer patient a therapeutically effective amount of a compound provided herein (e.g., a compound of formula (I), (Ia), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (IVb), (V), (Va), (VI), or (VIa)), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein. In some embodiments, this disclosure provides the use of compounds provided herein (e.g., compounds of formula (I), (Ia), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (IVb), (V), (Va), (VI), or (VIa)) or pharmaceutically acceptable salts thereof for the manufacture of medicaments for the treatment of IKFZ2-related diseases or conditions. In some embodiments, this disclosure provides the use of compounds provided herein (e.g., compounds of formula (I), (Ia), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (IVb), (V), (Va), (VI), or (VIa)) or pharmaceutically acceptable salts thereof in the manufacture of medicaments for the treatment of cancer. In some embodiments, this disclosure provides a compound provided herein (e.g., a compound of formula (I), (Ia), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (IVb), (V), (Va), (VI), or (VIa)), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound provided herein, for pharmaceutical use. In some embodiments, this disclosure provides a compound provided herein (e.g., a compound of formula (I), (Ia), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (IVb), (V), (Va), (VI), or (VIa)), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound provided herein, for the treatment of IKFZ2-related diseases or conditions. In some embodiments, this disclosure provides a compound provided herein (e.g., a compound of formula (I), (Ia), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (IVb), (V), (Va), (VI), or (VIa)), a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound provided herein for the treatment of cancer. This disclosure relates to degraders of IKAROS family zinc finger (IKZF) proteins, such as IKZF2 (Helios) . This disclosure also relates to compositions and methods relating to IKZF2 protein degraders and the use of such compounds for the treatment and / or prevention of IKZF2-mediated diseases and conditions. This disclosure further relates to compositions and methods for the treatment and / or prevention of cancer or viral infections, comprising combinations of IKZF2 protein degraders with one or more additional therapeutic agents. It is generally believed that patients with certain IKZF2-mediated diseases (such as cancer and viral infections) can benefit from treatment with IKZF2 protein degraders and optionally one or more additional therapeutic agents. Definition and general parameters The following description is made under the understanding that this disclosure is considered as an example of the claimed claims and is not intended to limit the scope of the accompanying claims to the specific embodiments described. The headings used throughout this disclosure are provided for convenience and should not be construed as limiting the scope of the claims in any way. Embodiments described under any heading may be combined with embodiments described under any other heading. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. It should be noted that, as used herein and in the appended claims, the singular forms “a / an” and “the” include plural references unless the context clearly indicates otherwise. Thus, for example, reference to “the compound” includes a plural of such compounds, and reference to “the assay” includes one or more assays and their equivalents known to one of ordinary skill in the art, etc. As used in this specification, the following terms and phrases are generally intended to have the meanings set forth below, unless otherwise indicated in the context in which they are used. A hyphen ("-") not between two letters or symbols is used to indicate the attachment point of a substituent. For example, -CONH 2. Attachment via carbon atoms. The dashes before or at the end of chemical groups are for convenience; chemical groups may or may not be depicted with one or more dashes without losing their usual meaning. Wavy lines drawn through the structure indicate the attachment points of groups. Unless required by chemical or structural rules, the order in which chemical groups are written or named does not indicate or imply directionality. Solid lines extending from the center of the ring indicate that the attachment point of a substituent on the ring can be at any ring atom. For example, in the following structure, R... a It can be attached to any of the five carbon ring atoms or R aHydrogen atoms that can be displaced and attached to nitrogen ring atoms: . Such as the prefix "C" u-v "" indicates that the following group has u to v carbon atoms. For example, "C 1-6 "Alkyl" indicates that an alkyl group has 1 to 6 carbon atoms. Similarly, the term "x- to y-membered" ring, where the values ​​of x and y coefficients range (such as "3- to 12-membered heterocyclic"), refers to a ring containing x to y atoms (e.g., 3 to 12), of which up to 80% may be heteroatoms such as N, O, S, and P, while the remaining atoms are carbon. In addition, certain commonly used alternative chemical names may or may not be used. For example, divalent groups such as divalent "alkyl" and divalent "aryl" may also be referred to as "alkylene / alkylenyl / alkylyl" and "arylene / arylenyl / arylyl", respectively. "A compound disclosed herein," "a compound of the present disclosure," "a compound provided herein," or "a compound described herein" refers to compounds of formula (I), (Ia), (Ib), or (Ic). It also includes the specific compounds of Examples 1 to 339 provided herein. The use of "about" as a value or parameter in this document includes (and describes) embodiments for that value or parameter itself. In some embodiments, the term "about" includes an indication of ±10%. In other embodiments, the term "about" includes an indication of ±5%. In some still embodiments, the term "about" includes an indication of ±1%. Furthermore, the term "about X" includes a description of "X". Additionally, the singular forms "a" and "the" both include plural references unless the context clearly indicates otherwise. Thus, for example, referring to "the compound" includes a plural of such compounds, and referring to "the test" includes referring to one or more tests and their equivalents known to those skilled in the art. "alkyl" refers to unbranched or branched saturated hydrocarbon chains. As used herein, alkyl groups have 1 to 20 carbon atoms (i.e., C64-C ... 1-20 Alkyl groups, or 1 to 8 carbon atoms (i.e., C646) 1-8 Alkyl groups, 1 to 6 carbon atoms (i.e., C64) 1-6 Alkyl groups, 1 to 4 carbon atoms (i.e., C46) 1-4 Alkyl groups), or 1 to 3 carbon atoms (i.e., C464) 1-3 Alkyl groups. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, secondary butyl, isobutyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue with a specific number of carbons is named by a chemical name or determined by a molecular formula, it can encompass isomers with all positions having that number of carbons. Thus, for example, "butyl" includes n-butyl (i.e., -(CH3)2) 2) 3CH 3) Secondary butyl (i.e., -CH(CH) 3)CH 2CH 3) Isobutyl (i.e., -CH) 2CH(CH 3) 2) and tertiary butyl (i.e. -C(CH) 3) 3); and "propyl" includes n-propyl (i.e., -(CH) 2) 2CH 3) and isopropyl (i.e., -CH(CH) 3) 2). "Alkenyl" refers to a group containing at least one carbon-carbon double bond and having 2 to 20 carbon atoms (i.e., C atoms). 2-20 alkenyl), 2 to 8 carbon atoms (i.e., C 2-8 alkenyl), 2 to 6 carbon atoms (i.e., C 2-6 alkenyl), or 2 to 4 carbon atoms (i.e., C). 2-4 Alkenyl groups are aliphatic groups. Examples of alkenyl groups include vinyl, propenyl, and butadienyl (including 1,2-butadienyl and 1,3-butadienyl). "Alkynyl" refers to a group containing at least one carbon-carbon linkage and having 2 to 20 carbon atoms (i.e., C20). 2-20alkynyl group), 2 to 8 carbon atoms (i.e., C 2-8 alkynyl group), 2 to 6 carbon atoms (i.e., C64) 2-6 (alkynyl group), or 2 to 4 carbon atoms (i.e., C46) 2-4 Alkynyl is an aliphatic group. The term "alkynyl" also includes groups having one triple bond and one double bond. "Acyl" refers to the group -C(=O)R, where R is hydrogen, alkyl, cycloalkyl, heterocyclic, aryl, heteroalkyl, or heteroaryl; each may optionally be substituted, as defined herein. Examples of acyl groups include methylacyl, acetylated, cyclohexylcarbonyl, cyclohexylmethyl-carbonyl, and benzoyl. "Alkoxy" refers to an alkyl group having an oxygen atom attached to the alkyl group at the attachment point: alkyl-O-. Like alkyl groups, alkoxy groups will have any suitable number of carbon atoms, such as C. 1-6 Alkoxy groups include, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, 2-butoxy, isobutoxy, secondary butoxy, tertiary butoxy, pentoxy, and hexoxy. Alkoxy groups may be further substituted with the various substituents described herein. Alkoxy groups may be substituted or unsubstituted. "Alkoxyalkyl" refers to an alkoxy group attached to an alkyl group, which is then attached to the rest of the compound. Alkoxyalkyl groups have any suitable number of carbons, such as 2 to 6 (C6+). 2-6 alkoxyalkyl), 2 to 5 (C 2-5 alkoxyalkyl), 2 to 4 (C 2-4 alkoxyalkyl), or 2 to 3 (C 2-3 Alkoxyalkyl). The carbon number refers to the total number of carbons in the alkoxy and alkyl groups. For example, in some embodiments, C 6-alkoxyalkyl refers to the group linked to a butyl group (C 4-alkyl) ethoxy (C 2-alkoxy), and in other embodiments, n-propoxy (C 3-alkoxy group) linked to isopropyl group (C 3. Alkyl groups. Alkoxy and alkyl groups are as defined above, wherein the alkyl group is divalent and may include, but is not limited to, methoxymethyl (CH4). 3OCH 2-) Methoxyethyl (CH 3OCH 2CH 2-), and others. "Amino" refers to -NR y R z , where R y and R z It is independently selected from the group consisting of: hydrogen, alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocyclic; each of which may be optionally substituted. "Imino" refers to a group containing a carbon-nitrogen double bond and having the following structure. Where R 1 R 2 and R 3 It is independently selected from the group consisting of: hydrogen, alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocyclic; each of which may optionally be substituted. R 1 R 2 and R 3 Either of them can be used as an attachment point. As used herein, "aryl" refers to a monocyclic or polycyclic aromatic ring system, wherein at least one ring is aromatic. For example, in some embodiments, the aryl group has 6 to 20 carbon atoms, 6 to 14 carbon atoms, or 6 to 12 carbon atoms. Aryl groups include phenyl radicals. Aryl groups also include polycyclic ring systems (e.g., ring systems containing 2, 3, or 4 rings) having 9 to 20 carbon atoms (e.g., 9 to 16 carbon atoms), wherein at least one ring is aromatic, and wherein the other rings may be aromatic or non-aromatic (i.e., carbocyclic). Such polycyclic ring systems may optionally be substituted with one or more (e.g., 1, 2, or 3) side oxygen groups at any carbon ring portion of the polycyclic ring system. When valence requirements permit, the rings of a polycyclic ring system may be linked together by fusion, spiking, and bridging bonds. It is also understood that when referring to an aryl group with a certain atomic range (e.g., 6 to 10 members), that atomic range refers to all ring atoms of that aryl group. For example, a 6-membered aryl group would include a phenyl group, while a 10-membered aryl group would include a naphthyl group and a 1,2,3,4-tetrahydronaphthyl group. Non-limiting examples of aryl groups include, but are not limited to, phenyl, indenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, anthraceneyl, and the like. "Cyano" or "carbonitrile" refers to the -CN group. "Cycloalkyl" refers to a saturated or partially saturated cyclic alkyl group having a single or multiple rings, including fused, bridged, and spirocyclic systems. The term "cycloalkyl" also includes cycloalkenyl groups (i.e., cyclic groups having at least one double bond). As used herein, cycloalkyl groups have 3 to 20 cyclic carbon atoms (i.e., C64 carbon atoms). 3-20 cycloalkyl groups), 3 to 12 cyclic carbon atoms (i.e., C12) 3-12 cycloalkyl groups), 3 to 10 cyclic carbon atoms (i.e., C1456) 3-10 cycloalkyl groups), 3 to 8 cyclic carbon atoms (i.e., C1646) 3-8 cycloalkyl groups), or 3 to 6 cyclic carbon atoms (i.e., C1646) 3-6 Cycloalkyl groups. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. "Fused" refers to a ring bonded to an adjacent ring. In some embodiments, the fused ring system is a heterocyclic group. In some embodiments, the fused ring system is an oxabiscyclohexyl group. In some embodiments, the fused ring system is... or . "Bridged" refers to a ring fusion in which non-adjacent atoms on a ring are joined by a divalent substituent (such as an alkyl group, or an alkyl group containing one or two heteroatoms, or a single heteroatom). Examples of pyridyl and adamantyl-based bridged ring systems. In some embodiments, the bridged ring system is bicyclopentyl (e.g., bicyclo[1.1.1]pentyl), bicycloheptyl (e.g., bicyclo[2.2.1]heptyl, bicyclo[3.1.1]heptyl), or bicyclooctyl (e.g., bicyclo[2.2.2]octyl). In some embodiments, the bridged ring... , , , ,or . "Spiro" refers to a cyclic substituent formed by two bonds bonded together at the same carbon atom. Examples of spiro groups include 1,1-diethylcyclopentane and dimethyl-2-diethylcyclopentane. And 4-benzyl-4-methylpiperidine, wherein cyclopentane and piperidine are spiro-substituents, respectively. In some embodiments, the spiro-substituent is spiropentyl (spiropentyl), spirohexyl, spiropentyl, spiroctyl (e.g., spiropentyl[2.5]octyl), spirononyl (e.g., spiropentyl[3.5]nonyl), spirdecyl (e.g., spiropentyl[4.5]decyl), or spiroundecyl (e.g., spiropentyl[5.5]undecyl). In some embodiments, the spiro-substituent is , , , , , , , ,or . "Halogen" or "halo" includes fluorine, chlorine, bromine, and iodine groups. As used herein, "haloalkyl" means an alkyl group as defined herein, wherein one or more hydrogen atoms of the alkyl group are independently replaced by halogen substituents (which may be the same or different). For example, C 1-4 Halogenated C 1-4 Alkyl, wherein C 1-4 One or more hydrogen atoms of the alkyl group have been replaced by a halogen substituent. Examples of alkyl halogens include, but are not limited to, fluoromethyl, fluorochloromethyl, difluoromethyl, difluorochloromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, and pentafluoroethyl. "Haloalkoxy" refers to an alkoxy group in which some or all of the hydrogen atoms are replaced by halogen atoms. Like alkyl groups, haloalkoxy groups can have any suitable number of carbon atoms, such as C0. 1-6 Alkyl groups can be substituted with one, two, three, or more halogens. When all hydrogens are replaced by a halogen, such as fluorine, the compound undergoes total substitution, such as perfluorination. Haloalkoxy groups include, but are not limited to, trifluoromethoxy, 2,2,2-trifluoroethoxy, and perfluoroethoxy. As used herein, the term "heteroaryl" refers to a monoaromatic or polycyclic aromatic ring. This term includes monoaromatic rings having about 1 to 6 carbon atoms and about 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. Sulfur and nitrogen atoms may also exist in oxidized forms, provided the ring is cyclic aromatic. Such rings include, but are not limited to, pyridyl, pyrimidinyl, and... Azolyl or furanyl. This term also includes polycyclic systems (e.g., systems containing 2 or 3 rings), wherein the heteroaryl group as defined above may be associated with one or more heteroaryl groups (e.g., ...). The heteroaryl polycyclic ring is fused with a pyridyl group, a carbocyclic ring (e.g., 5,6,7,8-tetrahydroquinolinyl), or an aryl group (e.g., indazole group) to form a polycyclic ring. Such polycyclic rings may optionally be substituted with one or more (e.g., 1, 2, or 3) side oxygen groups on the carbocyclic portion of the polycyclic ring. It should be understood that the attachment point of the heteroaryl polycyclic ring as defined above can be at any position on the ring, including the heteroaryl, aryl, or carbocyclic portion of the ring. Exemplary heteroaryl groups include, but are not limited to, pyridyl, pyrrole, and pyridine. pyrazinyl, pyrimidinyl, pyrazinyl pyridazinyl, pyrazolyl, thiophene, indole, imidazole, azole group, thiazolyl group, furanyl group, diazolyl (oxadiazolyl), thiadiazolyl, quinolinyl, isoquinolinyl, benzothiazolyl, benzo[a] benzoxazolyl, indazole, quinolone Quinoxalyl, quinazolyl, 5,6,7,8-tetrahydroisoquinolinylbenzofuranyl, benzimidazolyl, and thianaphthenyl. As used herein, "heterocyclyl" or "heterocyclic ring / heterocycle" refers to a single saturated or partially unsaturated ring or a polycyclic ring. This term includes a single saturated or partially unsaturated ring (e.g., 3, 4, 5, 6, or 7-membered ring) having about 1 to 6 carbon atoms and about 1 to 3 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur. The ring may be substituted with one or more (e.g., 1, 2, or 3) side oxygen groups, and the sulfur and nitrogen atoms may also be present in their oxidized forms. Such rings include, but are not limited to, acrylyl, tetrahydrofuranyl, or piperidinyl. This term also includes polycyclic ring systems (e.g., ring systems containing 2 or 3 rings), wherein the heterocyclic group (as defined above) may be associated with one or more heterocycles (e.g., decahydrogenated rings). pyridyl), heteroaryl (e.g., 1,2,3,4-tetrahydro), A pyridyl group, a carbocyclic ring (e.g., decahydroquinolinyl), or an aryl group is attached to two adjacent atoms (fused heterocycle). It should be understood that the attachment point of a heterocyclic polycyclic ring as defined above can be anywhere on the ring, including the heterocyclic part of the ring, the heteroaryl group, the aryl group, or the carbocyclic portion. Exemplary heterocycles include, but are not limited to, aziridinyl, acrylyl, pyrrolidyl, piperidinyl, ciperidinyl, N- linyl, thioN- porinoyl, piperin group, tetrahydrofuranyl, dihydro Azolyl, tetrahydropiperanyl, tetrahydrothiaranyl, 1,2,3,4-tetrahydroquinolinyl, benzo[] dihydrogen azole group, 1,2-Dihydropyridyl, 2,3-Dihydrobenzofuranyl, 1,3-benzodi ethyl, and 1,4-benzodi Alkyl groups. Exemplary fused bicyclic heterocycles include, but are not limited to, those shown below. , , , , , , , , , , , , , , , . "Hydroxy" refers to the -OH group. "Oxo" refers to the group (=O) or (O). "sulfonyl" refers to the -S(O) group. 2R c , where R c It is an alkyl, heterocyclic, cycloalkyl, heteroaryl, or aryl group. Examples of sulfonyl groups are methanesulfonyl, ethanesulfonyl, benzenesulfonyl, and toluenesulfonyl. Unless otherwise indicated, whenever the graphical representation of a group ends with a single bonded nitrogen atom, the group represents -NH. 2. Group. Similarly, unless otherwise indicated, hydrogen atoms are implied as and considered to be present, as required by the knowledge of one of ordinary skill in the art, to complete the valence or to provide stability. The terms "optional" or "optionally" mean that the event or situation described below may or may not occur, and the description includes both the possibility that the event or situation occurs and the possibility that it does not occur. Furthermore, the term "optionally substituted" means that any one or more hydrogen atoms on a specified atom or group may or may not be partially substituted with hydrogen atoms. The term "substituted" means that one or more hydrogen atoms on a specified atom or group are replaced by one or more substituents other than hydrogen, provided that the replacement does not exceed the normal valence of the specified atom. One or more substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acetyl, amino, acetamyl, formamidinyl, aryl, azide, aminomethyl, carboxyl, carboxyl ester, cyano, guanidinyl, haloyl, haloalkyl, heteroalkyl, heteroaryl, heterocyclic, hydroxyl, hydrazyl, imino, syloxy, nitro, alkylsulfinyl, sulfonic acid, alkylsulfonyl, thiocyanate, thiol, thion, or combinations thereof. Polymers or similar infinite structures obtained by defining substituents by an unlimited number of additional substituents (e.g., a substituted aryl group having a substituted alkyl group, which itself is substituted by a substituted aryl group, which is further substituted by a substituted heteroalkyl group, etc.) are not intended to be included herein. Unless otherwise stated, the maximum number of successive substitutions in the compounds described herein is three. For example, a substituted aryl group that is successively substituted with two other substituted aryl groups is limited to an aryl group substituted with ((substituted aryl) substituted) aryl group. Similarly, the above definition is not intended to include prohibited substitution patterns (e.g., a methyl group substituted with five fluorine atoms or a heteroaryl group having two adjacent oxygen ring atoms). Such prohibited substitution patterns are well known to those skilled in the art. When used to modify chemical groups, the term "substituted" may describe other chemical groups as defined herein. For example, the term "substituted aryl" includes, but is not limited to, "alkylaryl". Unless otherwise stated, when a group is described as optionally substituted, any substituted element of that group is itself unsubstituted. In some embodiments, the term "substituted alkyl" refers to an alkyl group having one or more substituents (including hydroxyl, halogen, amino, alkoxy, cycloalkyl, heterocyclic, aryl, and heteroaryl). In additional embodiments, "substituted cycloalkyl" refers to a cycloalkyl group having one or more substituents (including alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, amino, alkoxy, halo, septoxy, and hydroxy); "substituted heterocyclyl" refers to a heterocyclyl group having one or more substituents (including alkyl, amino, haloalkyl, heterocyclyl, cycloalkyl, aryl, heteroaryl, alkoxy, halo, septoxy, and hydroxy); "substituted aryl" refers to an aryl group having one or more substituents (including halo, alkyl, amino, haloalkyl, cycloalkyl, heterocyclyl, heteroaryl, alkoxy, and cyano); "substituted heterocyclyl" refers to a aryl group having one or more substituents (including halo, alkyl, amino, haloalkyl, cycloalkyl, heterocyclyl, heteroaryl, alkoxy, and cyano); "Heteroaryl" refers to a heteroaryl group having one or more substituents (including halogen, amino, alkyl, haloalkyl, cycloalkyl, aryl, heterocyclic, heteroaryl, alkoxy, and cyano), and "substituted sulfonyl" refers to the group -S(O). 2R, wherein R is substituted with one or more substituents (including alkyl, cycloalkyl, heterocyclic, aryl, and heteroaryl). In other embodiments, one or more substituents may be further substituted with a halogroup, alkyl, haloalkyl, hydroxyl, alkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl, each of which is substituted. In other embodiments, the substituents may be further substituted with a halogroup, alkyl, haloalkyl, alkoxy, hydroxyl, cycloalkyl, heterocyclic, aryl, or heteroaryl, each of which is unsubstituted. In some embodiments, the substituted cycloalkyl, substituted heterocyclic, substituted aryl, and / or substituted heteroaryl groups include cycloalkyl, heterocyclic, aryl, and / or heteroaryl groups having substituents on the ring atom, which attach the cycloalkyl, heterocyclic, aryl, and / or heteroaryl group to the remainder of the compound. For example, in the following portions, the cyclopropyl group is methyl-substituted: . The disclosures illustrated herein may be suitably applied where no element or elements, limitation or limitations not specifically disclosed herein are present. Therefore, for example, the terms "comprising," "including," and "containing" should be interpreted broadly and without limitation. Furthermore, the terms and expressions used herein are descriptive rather than limiting, and their use is not intended to exclude any equivalents of the features shown and described or any part thereof, but it is recognized that various modifications are possible within the scope of the claims made herein. The compounds disclosed herein may be in the form of pharmaceutically acceptable salts. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable, non-toxic bases or acids (including inorganic bases or acids and organic bases or acids). Where the compounds disclosed herein contain one or more acidic or basic groups, this disclosure also includes their corresponding pharmaceutically or toxicologically acceptable salts, particularly their pharmaceutically usable salts. Therefore, compounds of this disclosure containing acidic groups may be present on these groups and may be used according to this disclosure as, for example, alkali metal salts, alkaline earth metal salts, or ammonium salts. More precise examples of such salts include salts of sodium, potassium, calcium, magnesium, or ammonia or organic amines (such as, for example, ethylamine, ethanolamine, triethanolamine, amino acids, or other bases known to those skilled in the art). Compounds disclosed herein may contain one or more basic groups (i.e., protonable groups) and may be used according to this disclosure as addition salts of inorganic or organic acids. Examples of suitable acids include hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, nitric acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acid, oxalic acid, acetic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, formic acid, propionic acid, trimethylacetic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid, malic acid, aminosulfonic acid, phenylpropionic acid, gluconic acid, ascorbic acid, isonicotinic acid, citric acid, adipic acid, and other acids known to those skilled in the art. If the compounds disclosed herein contain both acidic and basic groups in their molecules, then in addition to the salt forms mentioned, this disclosure also includes internal salts or betaine (zwitterions). Individual salts can be obtained by conventional methods known to those skilled in the art, such as by contacting them with organic or inorganic acids or bases in a solvent or dispersant, or by anion or cation exchange with other salts. This disclosure also includes all salts of the compounds disclosed herein that are not directly suitable for use as pharmaceuticals due to low physiological compatibility, but can be used, for example, as intermediates in chemical reactions or for the preparation of pharmaceutically acceptable salts. Acids and bases that can be used to react with the base compound to form pharmaceutically acceptable salts (acid addition or base addition salts, respectively) are known to those skilled in the art. Similarly, methods for preparing pharmaceutically acceptable salts from the base compound (according to the disclosure) are known to those skilled in the art and are disclosed, for example, in Berge, at al. Journal of Pharmaceutical Science, Jan. 1977 vol. 66, No. 1 and other sources. Furthermore, the compounds disclosed herein are capable of tautomerism. When a compound or its prodrug is capable of tautomerism (e.g., keto-enol tautomerism), the individual forms (such as keto and enol forms) and mixtures thereof in any proportion are within the scope of this disclosure. This also applies to stereoisomers, such as mirror-image isomers, cis / trans isomers, non-mirror-image isomers, configurational isomers, and the like. The term "protecting group" refers to a portion of a compound that masks or alters the properties of functional groups or the entire compound. Chemical protecting groups and the strategies used for protection / deprotection are well known in the field. See, for example, *Protective Groups in Organic Chemistry*, *Theodora W. Greene, John Wiley & Sons*, Inc., New York, 1991. Protecting groups are typically used to mask the reactivity of certain functional groups to improve the efficiency of a desired chemical reaction, such as by creating and breaking chemical bonds in an ordered and planned manner. The term "deprotecting" refers to the removal of a protecting group. Those skilled in the art will understand that when a list of substituents includes members that cannot be used to substitute a particular group due to their valence requirements or other reasons, it is intended to interpret the list using the knowledge of those skilled in the art to include only those members suitable for substituting a particular group. Furthermore, the compounds disclosed herein may exist in the form of solvates, such as water solvates, or pharmaceutically acceptable solvates, such as alcohols, particularly ethanol. A "solvate" is formed by the interaction of a solvent and a compound. In some embodiments, optical isomers, racemic derivatives, or other mixtures thereof (e.g., non-racemic mixtures) of the compounds described herein, or pharmaceutically acceptable salts or mixtures thereof, are provided. If desired, the isomers can be separated by methods well known in the art (e.g., liquid chromatography). In these cases, a single mirror-image isomer or a non-mirror-image isomer (i.e., the optically active form) can be obtained by asymmetric synthesis or by resolution. Resolution can be accomplished by, for example, conventional methods, such as crystallization in the presence of a resolving agent, or chromatography using, for example, a microscopic high-performance liquid chromatography (HPLC) column. "Stereoisomer" refers to a compound consisting of identical atoms bonded by the same bonds but with different three-dimensional structures, and such compounds are not interchangeable. This invention envisions various stereoisomers and mixtures thereof, including "enantiomers," which are non-overlapping mirror images of each other. "Diastereomers" are stereoisomers having at least two asymmetric atoms but not being mirror images of each other. Unless otherwise specified, this description is intended to include individual stereoisomers and mixtures. Methods for determining stereochemistry and separating stereoisomers are well known in the art (see, for example, Chapter 4 of Advanced Organic Chemistry, 4th ed., J. March, John Wiley and Sons, New York, 1992). The compounds disclosed herein and their pharmaceutically acceptable salts may include one or more asymmetric centers in some embodiments, and thus may produce mirror-image isomers, non-mirror-image isomers, and other stereoisomers, which can be defined by absolute stereochemistry as ( R)-or ( S)-, or defined for amino acids as (D)- or (L)-. Some examples include all such possible isomers, as well as their racemic, non-racemic, and optically pure forms. Optically active (+) and (-), ( R)- and ( S-, or (D)- and (L)- isomers can be prepared using a palmitic synthetic component or a palmitic reagent, or resolved using conventional techniques such as chromatography and fractional crystallization. Conventional techniques for preparing / isolating individual mirror-image isomers include the palmitic synthesis or resolution of racemic products (or racemic products of salts or derivatives) from suitable optically pure precursors using, for example, palmitic high-pressure liquid chromatography (HPLC). When the compounds described herein contain olefinic double bonds or other geometrically asymmetric centers, unless otherwise specified, such compounds are intended to include both E and Z geometric isomers. Similarly, all tautomeric forms are intended to be included. When a compound is expressed in its palmitic form, it should be understood that the examples cover, but are not limited to, specific non-mirror-image isomers or enriched forms of mirror-image isomers. When palmiticity is not specified but present, it should be understood that the examples relate to specific non-mirror-image isomers or enriched forms of mirror-image isomers; or racemic or non-racemic mixtures of such compounds. As used herein, a "scalemic mixture" is a mixture of stereoisomers in a non-1:1 ratio. For example, in some embodiments, the compounds... The term "system" is understood to encompass specific non-mirror isomers or mirror isomer enrichment forms; or isomers. A and isomers B Racemic or non-racemic mixtures. The compositions provided herein, including the compounds described herein or their pharmaceutically acceptable salts, isomers, or mixtures thereof, may include racemic mixtures, or mixtures containing an excess of one mirror-image isomer or a single non-mirror-image isomer or a mixture of non-mirror-image isomers. All such isomers of these compounds are expressly included herein, as each and every isomer is specifically and individually listed. Any formula or structure given herein is intended to represent both unlabeled and isotopically labeled forms of the compound. Isotopically labeled compounds have the structures shown in the formulas given herein, except that one or more atoms are replaced by atoms having selected atomic masses or mass numbers. Examples of isotopes that may be incorporated into the compounds disclosed herein include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as, but not limited to, isotopes of these elements. 2 H (deuterium, D) 3 H (tritium) 11 C 13 C 14 C 15 N、 18 F, 31 P, 32 P, 35 S, 36 Cl, and 125 I. The various isotopically labeled compounds disclosed herein, such as those incorporating radioactive isotopes (e.g., 3 H, 13 C, and 14 C) These isotopically labeled compounds can be used in metabolic studies, reaction kinetic studies, detection or imaging techniques (such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT)), including drug or receptor tissue distribution assays, or for radiotherapy of patients. The isotopically labeled compounds and their prodrugs disclosed herein can generally be prepared by performing the procedures disclosed in the following protocols or examples and preparations, and by replacing unlabeled reagents with readily available isotopically labeled reagents. This disclosure also includes "deuterated analogs" of the compounds disclosed herein, wherein one to n hydrogen atoms attached to carbon atoms are replaced with deuterium, where n represents the number of hydrogen atoms in the molecule. Such compounds can exhibit increased resistance to metabolism and are therefore used to increase the half-life of any compound of formula (I) when administered to mammals (e.g., humans). See, for example, Foster, “Deuterium Isotope Effects in Studies of Drug Metabolism,” Trends Pharmacol. Sci. 5(12):524-527 (1984). Such compounds are synthesized by means well known in the art, for example by using starting materials in which one or more hydrogen atoms have been replaced with deuterium. The deuterium-labeled or substituted therapeutic compounds disclosed herein can possess beneficial drug metabolism and pharmacokinetic (DMPK) properties, which are related to distribution, metabolism, and excretion (ADME). Substitution with a heavier isotope (such as deuterium) can provide certain therapeutic advantages due to higher metabolic stability, such as increased in vivo half-life, reduced dose requirement, and / or improved therapeutic index. 18 Compounds marked with F can be used in PET or SPECT studies. The concentration of this heavier isotope (specifically deuterium) can be defined by the isotope enrichment factor. In the compounds disclosed herein, any atom not specifically designated as a particular isotope is intended to represent any stable isotope of that atom. Unless otherwise stated, when a position is specifically designated as "H" or "hydrogen," that position is understood to have hydrogen in its naturally abundant isotopic composition. Therefore, in the compounds disclosed herein, any atom specifically designated as deuterium (D) is intended to represent deuterium. In addition, this disclosure provides pharmaceutical compositions comprising the compounds disclosed herein, or their prodrug compounds, or their pharmaceutically acceptable salts or solvates as active ingredients and pharmaceutically acceptable carriers. "Pharmaceutical composition" refers to one or more active ingredients, one or more inert ingredients constituting a carrier, and any product directly or indirectly produced by the combination, compounding, or aggregation of any two or more ingredients, the dissociation of one or more ingredients, or other types of reactions or interactions of one or more ingredients. Therefore, the pharmaceutical composition disclosed herein may encompass any composition made by mixing at least one of the compounds disclosed herein with a pharmaceutically acceptable carrier. As used herein, "pharmaceutically acceptable carrier" includes excipients or agents that are harmless to the disclosed compound or its intended use, such as solvents, diluents, dispersion media, coatings, antibacterial and antifungal agents, isotropic and absorption-retarding agents, and the like. The use of such carriers and agents in the preparation of compositions of pharmaceutically active substances is well known in the art (see, for example, Remington's Pharmaceutical Sciences, Mace Publishing Co., Philadelphia, PA 17th Ed. (1985); and Modern Pharmaceutics, Marcel Dekker, Inc. 3rd Ed. (GS Banker & CT Rhodes, Eds.). IC 50 "or "EC" 50 "This refers to the inhibitory concentration required to achieve 50% of the maximum desired effect. In many cases in this paper, the maximum desired effect is IKZF2 protein degradation. This terminology was obtained using in vitro protein degradation assays (such as the HiBiT protein tag assay) that assess the concentration-dependent degradation of IKZF2 protein." max "This refers to the degradation of the largest protein (e.g., IKZF2 or IKZF1 protein) at the highest compound concentration tested in the assay." "Treatment / treating" refers to methods used to achieve beneficial or desired outcomes, including clinical outcomes. Beneficial or desired clinical outcomes may include one or more of the following: a) suppressing a disease or condition (e.g., reducing one or more symptoms arising from the disease or condition, and / or reducing the severity of the disease or condition); b) slowing or halting the development of one or more clinical symptoms associated with the disease or condition (e.g., stabilizing the disease or condition, preventing or delaying the worsening or progression of the disease or condition, and / or preventing or delaying the spread of the disease or condition (e.g., metastasis)); and / or c) alleviating the disease, i.e., the cessation of clinical symptoms (e.g., improving the disease state, providing partial or overall remission of the disease or condition, increasing...). To enhance the effect of another drug, delay disease progression, improve quality of life, and / or prolong survival. In some embodiments, the term "treatment" means administering a compound or pharmaceutically acceptable salt of formula (I), (Ia), (Ib), or (Ic) for the purpose of: (i) delaying the onset of disease, i.e., preventing or delaying the development of clinical symptoms of the disease; (ii) inhibiting the disease, i.e., preventing the development of clinical symptoms; and / or (iii) alleviating the disease, i.e. causing the reduction of clinical symptoms or their severity. "Prevention" means any treatment that prevents the development of clinical symptoms of a disease or condition. In some embodiments, the compound may be administered to a subject (including humans) who is at risk or has a family history of the disease or condition. As used herein, "IKZF-related disease or condition" (e.g., IKZF2 or IKZF4-related disease or condition) refers to a disease or condition whose improvement is achieved by a reduction in IKZF protein levels (e.g., IKZF2 or IKZF4 protein levels). In some embodiments, in an IKZF-related disease or condition, degradation of the IKZF2 protein can improve the disease or condition. In some embodiments, in an IKZF-related disease or condition, degradation of the IKZF2 protein and one or more additional IKZF proteins (e.g., IKZF4 protein) can improve the disease or condition. In some embodiments, in an IKZF-related disease or condition, degradation of the IKZF4 protein can improve the disease or condition. "Subject" means an animal, such as a mammal (including a human), that has become or will become a subject of treatment, observation, or experimentation. The methods described herein can be used for human therapeutics and / or veterinary applications. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. The term "therapeutically effective amount" or "effective amount" as used herein for compounds, pharmaceutically acceptable salts, tautomers, stereoisomers, mixtures of stereoisomers, prodrugs, or deuterated analogs thereof means an amount sufficient, when administered to a subject, to effectively treat and provide therapeutic benefits (such as improvement of symptoms or slowing of disease progression). For example, a therapeutically effective amount may be an amount sufficient to reduce the symptoms of a disease or condition that responds to an IKZF2 degrader. Therapeuticly effective amounts can vary depending on the subject being treated and the disease or condition, the subject's weight and age, the severity of the disease or condition, and the method of administration, and can be readily determined by someone skilled in the art. As used herein, "degrader" or "protein degrader" refers to any agent capable of binding to and inducing the degradation of a protein. Generally, protein degraders are believed to induce the degradation of targeted proteins through recruitment of cellular ubiquitination and proteasome protein degradation mechanisms. For example, as used herein, "IKZF2 degrader" or "IKZF2 protein degrader" refers to any agent capable of binding to and inducing the degradation of the IKZF2 protein. In some embodiments, the IKZF2 degrader is IKZF2 selective. In some embodiments, the IKZF2 degrader can induce the degradation of the IKZF2 protein and one or more additional IKZF2 proteins (e.g., IKZF1 or IKZF4). IKZF2 (also known as Helios) is a zinc finger transcription factor of the IKAROS family, generally believed to be necessary for maintaining a stable Treg cell phenotype, especially in the inflammatory tumor microenvironment. In humans, the IKZF2 or Helios protein is encoded by the IKZF2 gene. Exemplary reference sequences for IKZF2 (NCBI gene ID: 22807 (human); 22779 (mouse)) include NCBI reference sequences NP_001072994 (human protein), NP_035900 (mouse protein), NM_001079526 (human mRNA), and NM_0011770 (mouse mRNA). Related family members include IKZF1 (Ikaros; NCBI gene ID: 10320 (human); 22778 (mouse)) and IKZF4 (Eos; NCBI gene ID: 64375 (human); 22781 (mouse)). The activity of IKZF (e.g., IKZF2) degraders can be measured by methods known in the art, such as those described and cited in Wang In some embodiments, IKZF protein degradation is measured using HiBiT protein tagging assays (such as the Nano Glo® HiBiT extracellular detection system (Promega)). Spalt-like protein 4 (SALL4) is a member of the Spalt (SALL) family of zinc finger transcription factors. In humans, the SALL4 protein is encoded by the SALL4 gene (NCBI gene ID: 57167). SALL4 is described in, for example, by Donovan. et al., 2018 eLife 7:e38430 and Matyskiela et al. 2020 Nat Struct Mol Biol 27, 319–322. SALL4 degradation activity can be measured by any method known in the art. In some embodiments, SALL4 protein degradation is measured using a HiBiT protein tag assay (such as the Nano Glo® HiBiT extracellular detection system (Promega)). List of abbreviations and initials compound In one state sample, this disclosure provides a compound of formula (I), (I) or its pharmaceutically acceptable salt, wherein: R 1 System-H; R 2 -H, -F, or -Cl; R 21 -H, -F, or -Cl; R 3 -H, -F, or -Cl; R 4a and R 4b Each can be independently of -H, halogen, -OH, or C. 1-6 Alkyl; Cyclic A-series C 3-10 Cycloalkyl or heterocyclic groups; n-series 0, 1, 2, 3, or 4; each R 5 Independent halogens, =O, =CH 2. -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, -O-(R) 51 ), or -N(R 51 (R) 52 ); where R 5 Each of = CH 2. Alkyl, alkenyl, cycloalkyl, alkoxy, haloalkyl, haloalkoxy, heterocyclic, aryl, or heteroaryl groups may optionally be derived from one to four identical or different R groups. 5a Replace; Each R 5a Independent halogens, -CN, C 1-6 Alkyl, C 6-10 aryl, or -O(R) 51 ); where each R can be the same or different 51 and R 52 Independent phylogenetic systems - H, C 1-6 Alkyl, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl; R 6 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 1a (R) 1b ), -S(O)(NR 1a (R) 1b -C(O)R 1c -S(O) 2)R 1c 、or -C(O)OR 1d , where R 6 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 2a (R) 2b ), -S(O)(NR 2a (R) 2b -C(O)R 2c S(O) 2)R 2c 、or -C(O)OR 2d , where R 7 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 20 heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, =O, imine, -NO 2. -N 3. -CN, -OR 3a -C(O)-R 3a -C(O)OR 3a -C(O)-N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + ,-N(R 3a )C(O)-R 3b -N(R) 3a )C(O)OR 3b -N(R) 3a )C(O)N(R 3b )(R 3c )、-N(R 3a )S(O) 2(R 3b )、-NR 3a S(O) 2N(R 3b )(R 3c )、-NR 3a S(O)​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​3; where each Z 1 Z 2 、or Z 3 The alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, =O, -NO 2. -CN, -N 3. -OR 3a -C(O)R 3a -C(O)OR 3a -C(O)N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + -N(R) 3a )-C(O)R 3b -N(R) 3a )C(O)O(R 3b )、-N(R 3a )C(O)N(R 3b )(R 3c )、-N(R 3a )S(O) 2(R 3b )、-N(R 3a )S(O) 2-N(R 3b )(R 3c )、-N(R 3a )S(O) 2O(R 3b )、-OC(O)R 3a 、-OC(O)OR 3a 、-OC(O)-N(R 3a )(R 3b )、-S-R 3a 、-S(O)R 3a 、-S(O)(NH)R 3a 、-S(O) 2R 3a 、-S(O) )2N(R 3a )(R 3b )、-S(O)(NR 3a )R 3b 、或-Si(R 3a ) 3; wherein Z 1aThe alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, lateral oxygen, -OH, -CN, -NO 2. -NH 2. -N 3. -SH, -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 2-6 alkenyl), -O(C) 2-6 alkynyl group), -O(C 3-15 cycloalkyl), -O (heterocyclic), -O (C 6-10 aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 2-6 alkenyl), -NH (C 2-6 ynyl group), -NH(C 3-15 cycloalkyl), -NH (heterocyclic), -NH (C 6-10 aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 1-8 (haloalkyl) 2. -N(C 2-6 alkenyl) 2. -N(C 2-6 (alkynyl group) 2. -N(C 3-15 cycloalkyl) 2. -N (heterocyclic group) 2. -N(C 6-10 Aryl) 2. -N (Heteroaryl) 2. -N(C 1-9 Alkyl)(C 1-8 Halogenated groups), -N(C) 1-9 Alkyl)(C 2-6 alkenyl), -N(C) 1-9 Alkyl)(C 2-6 alkynyl group), -N(C 1-9 Alkyl)(C 3-15 cycloalkyl), -N(C) 1-9 Alkyl (heterocyclic), -N(C) 1-9 Alkyl)(C 6-10 aryl), -N(C 1-9 Alkyl)(heteroaryl), -C(O)(C 1-9 Alkyl), -C(O)(C 1-8 Halogenated groups), -C(O)(C 2-6 alkenyl), -C(O)(C 2-6 ynyl group), -C(O)(C 3-15 cycloalkyl), -C(O)(heterocyclic), -C(O)(C 6-10 aryl), -C(O)(heteroaryl), -C(O)O(C 1-9 Alkyl), -C(O)O(C 1-8Halogenated alkyl groups), -C(O)O(C 2-6 alkenyl), -C(O)O(C 2-6 alkynyl group), -C(O)O(C 3-15 cycloalkyl), -C(O)O (heterocyclic), -C(O)O (C 6-10 aryl), -C(O)O (heteroaryl), -C(O)NH 2. -C(O)NH(C) 1-9 Alkyl), -C(O)NH(C 1-8 Halogenated groups), -C(O)NH(C 2-6 alkenyl), -C(O)NH(C 2-6 ynyl group), -C(O)NH(C 3-15 cycloalkyl), -C(O)NH (heterocyclic), -C(O)NH (C 6-10 aryl), -C(O)NH (heteroaryl), -C(O)N(C 1-9 alkyl) 2. -C(O)N(C 1-8 (haloalkyl) 2. -C(O)N(C 2-6 alkenyl) 2. -C(O)N(C 2-6 (alkynyl group) 2. -C(O)N(C 3-15 cycloalkyl) 2. -C(O)N (heterocyclic group) 2. -C(O)N(C 6-10 Aryl) 2. -C(O)N (Heteroaryl) 2. -NHC(O)(C 1-9 Alkyl), -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 2-6alkenyl), -NHC(O)(C 2-6 ynyl group), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (C 6-10 aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 alkenyl), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (C 6-10 aryl), -NHC(O)O(heteroaryl), -NHC(O)NH(C 1-9 alkyl), -NHC(O)NH(C 1-8 Halogenated groups), -NHC(O)NH(C 2-6 alkenyl), -NHC(O)NH(C 2-6 ), -NHC(O)NH(C 3-15 cycloalkyl), -NHC(O)NH (heterocyclic), -NHC(O)NH (C 6-10 aryl), -NHC(O)NH (heteroaryl), -NHS(O)(C 1-9 alkyl), -N(C) 1-9 Alkyl)(S(O)(C) 1-9 alkyl), -S(C 1-9 alkyl), -S(C 1-8 Halogenated groups), -S(C 2-6 alkenyl), -S(C 2-6 alkynyl group), -S(C 3-15 cycloalkyl), -S (heterocyclic), -S (C 6-10 aryl), -S(heteroaryl), -S(O)N(C 1-9 alkyl) 2. -S(O)(C 1-9 Alkyl), -S(O)(C 1-8 Halogenated groups), -S(O)(C 2-6 alkenyl), -S(O)(C 2-6 ynyl group), -S(O)(C 3-15 cycloalkyl), -S(O)(heterocyclic), -S(O)(C 6-10 Aryl), -S(O) (heteroaryl), -S(O) 2(C 1-9 Alkyl groups, -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 2-6 alkenyl), -S(O) 2(C 2-6 Alkyne group), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(C 6-10 Aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups), -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2; where Z 1bThe alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally have one to three carbon atoms. 1-9 Alkyl, C 1-8 Halogenated groups, halogens, -OH, -NH 2. -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 3-15 cycloalkyl), -O (heterocyclic), -O (aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 3-15 cycloalkyl), -NH (heterocyclic), -NH (aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 3-15 cycloalkyl) 2. -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (aryl), -NHC(O)O (heteroaryl), -NHC(O)NH(C 1-9 Alkyl groups), S(O) 2(C 1-9 Alkyl groups), -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups), -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2 Replacement; Each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c Independent phylogenetic system - H, C 1-9 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Substitution; wherein, unless otherwise specified, the aryl groups of the compounds of formula (I) are C 6-10 Aryl; wherein, unless otherwise specified, each heteroaryl group of the compound of formula (I) is a 5- to 12-membered heteroaryl group having one to four heteroatoms of N, O, or S; wherein, unless otherwise specified, each heterocyclic group of the compound of formula (I) is a 3- to 20-membered heterocyclic group having one to four heteroatoms of N, O, or S. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H, -F, or -Cl; R 21 System-H; R 3 -H, -F, or -Cl; R 4a and R 4b Each can be independently of -H, halogen, -OH, or C. 1-6 Alkyl; Cyclic A-series C 3-10 Cycloalkyl or heterocyclic groups; n-series 0, 1, 2, 3, or 4; each R 5 Independent halogens, =O, -CN, C 1-6 Alkyl, C 1-6 Halogenated, C 1-6 Haloalkoxy, C 1-6 Alkoxy, C 3-6 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, -O-(R) 51 ), or -N(R 51 (R) 52 ); where R 5 Each alkyl, cycloalkyl, alkoxy, haloalkyl, haloalkoxy, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different R groups. 5a Replace; Each R 5a Independent halogens, -CN, C 1-6 Alkyl, C 6-10 Aryl, or -O(R) 51 ); where each R can be the same or different 51 and R 52 Independent phylogenetic system - H, C 1-6 Alkyl, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl; R 6 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 1a (R) 1b ), -S(O)(NR 1a (R) 1b -C(O)R 1c -S(O) 2)R 1c 、or -C(O)OR 1d , where R 6 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl-C(O)N(R) 2a (R) 2b ), -S(O)(NR 2a (R) 2b -C(O)R 2c S(O) 2)R 2c 、or -C(O)OR 2d , where R 7 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 20 heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, =O, imine, -NO 2. -N 3. -CN, -OR 3a -C(O)-R 3a -C(O)OR 3a -C(O)-N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + ,-N(R 3a )C(O)-R 3b -N(R) 3a )C(O)OR 3b -N(R) 3a )C(O)N(R 3b (R) 3c ), -N(R 3a S(O) 2(R 3b -NR 3a S(O) 2N(R 3b (R) 3c -NR 3a S(O) 2O(R 3b -OC(O)R 3a -OC(O)OR 3a -OC(O)-N(R) 3a (R) 3b ), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R 3a (R) 3b ), -S(O)(NR 3a )R 3b -S(O)(NR) 3a )N(R 3b (R) 3c ), -SF 5. or -Si(R) 3a ) 3; where each Z 1 Z 2 、or Z 3 The alkyl, halogen, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups may each be optionally derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, =O, -NO 2. -CN, -N 3. -OR 3a -C(O)R 3a -C(O)OR 3a -C(O)N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + -N(R) 3a )-C(O)R 3b -N(R) 3a )C(O)O(R 3b ), -N(R 3a )C(O)N(R 3b (R) 3c ), -N(R 3a S(O) 2(R 3b ), -N(R 3a S(O) 2-N(R 3b (R) 3c ), -N(R 3a S(O) 2O(R 3b -OC(O)R 3a -OC(O)OR 3a -OC(O)-N(R) 3a (R) 3b ), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R 3a (R) 3b ), -S(O)(NR 3a )R 3b 、or -Si(R 3a ) 3; where Z 1a The alkyl, halogen, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups may each be optionally derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent C 1-9 Alkyl, C 1-8 halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 Cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, lateral oxygen, -OH, -CN, -NO 2. -NH 2. -N 3. -SH, -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 2-6 alkenyl), -O(C) 2-6 alkynyl group), -O(C 3-15 cycloalkyl), -O (heterocyclic), -O (C 6-10 aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 2-6 alkenyl), -NH (C 2-6 ynyl group), -NH(C 3-15 cycloalkyl), -NH (heterocyclic), -NH (C 6-10 aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 1-8 (haloalkyl) 2. -N(C 2-6 alkenyl) 2. -N(C 2-6 (alkynyl group) 2. -N(C 3-15 cycloalkyl) 2. -N (heterocyclic group) 2. -N(C 6-10 Aryl) 2. -N (Heteroaryl) 2. -N(C 1-9 Alkyl)(C 1-8Halogenated groups), -N(C) 1-9 Alkyl)(C 2-6 alkenyl), -N(C) 1-9 Alkyl)(C 2-6 alkynyl group), -N(C 1-9 Alkyl)(C 3-15 cycloalkyl), -N(C) 1-9 Alkyl (heterocyclic), -N(C) 1-9 Alkyl)(C 6-10 aryl), -N(C 1-9 Alkyl)(heteroaryl), -C(O)(C 1-9 Alkyl), -C(O)(C 1-8 Halogenated groups), -C(O)(C 2-6 alkenyl), -C(O)(C 2-6 ynyl group), -C(O)(C 3-15 cycloalkyl), -C(O)(heterocyclic), -C(O)(C 6-10 aryl), -C(O)(heteroaryl), -C(O)O(C 1-9 Alkyl), -C(O)O(C 1-8 Halogenated alkyl groups), -C(O)O(C 2-6 alkenyl), -C(O)O(C 2-6 alkynyl group), -C(O)O(C 3-15 cycloalkyl), -C(O)O (heterocyclic), -C(O)O (C 6-10 aryl), -C(O)O (heteroaryl), -C(O)NH 2. -C(O)NH(C) 1-9 Alkyl), -C(O)NH(C 1-8Halogenated groups), -C(O)NH(C 2-6 alkenyl), -C(O)NH(C 2-6 ynyl group), -C(O)NH(C 3-15 cycloalkyl), -C(O)NH (heterocyclic), -C(O)NH (C 6-10 aryl), -C(O)NH (heteroaryl), -C(O)N(C 1-9 alkyl) 2. -C(O)N(C 1-8 (haloalkyl) 2. -C(O)N(C 2-6 alkenyl) 2. -C(O)N(C 2-6 (alkynyl group) 2. -C(O)N(C 3-15 cycloalkyl) 2. -C(O)N (heterocyclic group) 2. -C(O)N(C 6-10 Aryl) 2. -C(O)N (Heteroaryl) 2. -NHC(O)(C 1-9 Alkyl), -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 2-6 alkenyl), -NHC(O)(C 2-6 ynyl group), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (C 6-10 aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6alkenyl), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (C 6-10 aryl), -NHC(O)O(heteroaryl), -NHC(O)NH(C 1-9 alkyl), -NHC(O)NH(C 1-8 Halogenated groups), -NHC(O)NH(C 2-6 alkenyl), -NHC(O)NH(C 2-6 ), -NHC(O)NH(C 3-15 cycloalkyl), -NHC(O)NH (heterocyclic), -NHC(O)NH (C 6-10 aryl), -NHC(O)NH (heteroaryl), -NHS(O)(C 1-9 alkyl), -N(C) 1-9 Alkyl)(S(O)(C) 1-9 alkyl), -S(C 1-9 alkyl), -S(C 1-8 Halogenated groups), -S(C 2-6 alkenyl), -S(C 2-6 alkynyl group), -S(C 3-15 cycloalkyl), -S (heterocyclic), -S (C 6-10 aryl), -S(heteroaryl), -S(O)N(C 1-9 alkyl) 2. -S(O)(C 1-9 Alkyl), -S(O)(C 1-8 Halogenated groups), -S(O)(C 2-6 alkenyl), -S(O)(C 2-6 ynyl group), -S(O)(C 3-15 cycloalkyl), -S(O)(heterocyclic), -S(O)(C 6-10 Aryl), -S(O) (heteroaryl), -S(O) 2(C 1-9 Alkyl groups), -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 2-6 alkenyl), -S(O) 2(C 2-6 Alkyne group), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(C 6-10 Aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups), -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2; where Z 1b The alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally have one to three carbon atoms. 1-9 Alkyl, C 1-8 Halogenated groups, halogens, -OH, -NH 2. -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 3-15 cycloalkyl), -O (heterocyclic), -O (aryl), -O (heteroaryl), -NH (C 1-9alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 3-15 cycloalkyl), -NH (heterocyclic), -NH (aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 3-15 cycloalkyl) 2. -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (aryl), -NHC(O)O (heteroaryl), -NHC(O)NH(C 1-9 Alkyl groups), S(O) 2(C 1-9 Alkyl groups), -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups), -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2 Replacement; Each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c Independent phylogenetic system - H, C 1-9 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Substitution; wherein, unless otherwise specified, the aryl groups of the compounds of formula (I) are C 6-10Aryl; wherein, unless otherwise specified, each heteroaryl group of the compound of formula (I) is a 5- to 12-membered heteroaryl group having one to four heteroatoms of N, O, or S; wherein, unless otherwise specified, each heterocyclic group of the compound of formula (I) is a 3- to 20-membered heterocyclic group having one to four heteroatoms of N, O, or S. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H, -F, or -Cl; R 3 -H, -F, or -Cl; R 4a and R 4b Each can be independently of -H, halogen, -OH, or C. 1-6 Alkyl; Cyclic A-series C 3-10 Cycloalkyl or heterocyclic groups; n-series 0, 1, 2, 3, or 4; each R 5 Independent halogens, =O, -CN, C 1-6 Alkyl, C 1-6 Halogenated, C 1-6 Haloalkoxy, C 3-6 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, -O-(R) 51 ), or -N(R 51 (R) 52 ); where R 5 Each alkyl, cycloalkyl, alkoxy, haloalkyl, haloalkoxy, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different R groups. 5a Replace; Each R 5a Independent halogens, -CN, C 1-6 Alkyl, C 6-10 Aryl, or -O(R) 51 ); where each R can be the same or different 51 and R 52 Independent phylogenetic system - H, C 1-6 Alkyl, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 Cycloalkyl, heterocyclic, -C(O)N(R) 1a (R) 1b ), -S(O)(NR 1a (R) 1b -C(O)R 1c -S(O) 2)R 1c 、or -C(O)OR 1d , where R 6 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 Cycloalkyl, heterocyclic, -C(O)N(R) 2a (R) 2b ), -S(O)(NR 2a (R) 2b -C(O)R 2c S(O) 2)R 2c 、or -C(O)OR 2d , where R 7 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 20 heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, =O, imine, -NO 2. -N 3. -CN, -OR 3a -C(O)-R 3a -C(O)OR 3a、-C(O)-N(R 3a )(R 3b )、-N(R 3a )(R 3b )、-N(R 3a ) 2(R 3b ) + ,-N(R 3a )C(O)-R 3b 、-N(R 3a )C(O)O-R 3b 、-N(R 3a )C(O)N(R 3b )(R 3c )、-N(R 3a )S(O) 2(R 3b )、-NR 3a S(O) 2N(R 3b )(R 3c )、-NR 3a S(O) 2O(R 3b )、-OC(O)R 3a 、-OC(O)OR 3a 、-OC(O)-N(R 3a )(R 3b )、-S-R 3a 、-S(O)R 3a 、-S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R 3a (R) 3b ), -S(O)(NR 3a )R 3b -S(O)(NR) 3a )N(R 3b (R) 3c ), -SF 5. or -Si(R) 3a ) 3; where each Z 1 Z 2 、or Z 3 The alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 芳基 , heteroaryl, =O, -NO 2. -CN, -N 3. -OR 3a 、-C(O)R 3a 、-C(O)O-R 3a 、-C(O)N(R 3a )(R 3b )、-N(R 3a )(R 3b )、-N(R 3a ) 2(R 3b ) + 、-N(R 3a )-C(O)R 3b 、-N(R 3a )C(O)O(R 3b )、-N(R 3a )C(O)N(R 3b )(R 3c )、-N(R 3a )S(O) 2(R 3b )、-N(R 3a )S(O) 2-N(R 3b )(R 3c )、-N(R 3a )S(O) 2O(R 3b )、-OC(O)R 3a 、-OC(O)OR 3a 、-OC(O)-N(R 3a )(R 3b), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R 3a (R) 3b ), -S(O)(NR 3a )R 3b 、or -Si(R 3a ) 3; where Z 1a The alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, lateral oxygen, -OH, -CN, -NO 2. -NH 2. -N 3. -SH, -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 2-6 alkenyl), -O(C) 2-6 alkynyl group), -O(C 3-15 cycloalkyl), -O (heterocyclic), -O (C 6-10 aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 2-6 alkenyl), -NH (C 2-6 ynyl group), -NH(C 3-15 cycloalkyl), -NH (heterocyclic), -NH (C 6-10 aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 1-8 (haloalkyl) 2. -N(C 2-6 alkenyl) 2. -N(C 2-6 (alkynyl group) 2. -N(C 3-15 cycloalkyl) 2. -N (heterocyclic group) 2. -N(C 6-10 Aryl) 2. -N (Heteroaryl) 2. -N(C 1-9 Alkyl)(C 1-8 Halogenated groups), -N(C) 1-9 Alkyl)(C 2-6 alkenyl), -N(C) 1-9 Alkyl)(C 2-6 alkynyl group), -N(C 1-9 Alkyl)(C 3-15 cycloalkyl), -N(C) 1-9 Alkyl (heterocyclic), -N(C) 1-9 Alkyl)(C 6-10 aryl), -N(C 1-9 Alkyl)(heteroaryl), -C(O)(C 1-9 Alkyl), -C(O)(C 1-8 Halogenated groups), -C(O)(C 2-6 alkenyl), -C(O)(C 2-6 ynyl group), -C(O)(C 3-15 cycloalkyl), -C(O)(heterocyclic), -C(O)(C 6-10 aryl), -C(O)(heteroaryl), -C(O)O(C 1-9 Alkyl), -C(O)O(C 1-8 Halogenated alkyl groups), -C(O)O(C 2-6 alkenyl), -C(O)O(C 2-6 alkynyl group), -C(O)O(C 3-15 cycloalkyl), -C(O)O (heterocyclic), -C(O)O (C 6-10 aryl), -C(O)O (heteroaryl), -C(O)NH 2. -C(O)NH(C) 1-9 Alkyl), -C(O)NH(C 1-8 Halogenated groups), -C(O)NH(C 2-6 alkenyl), -C(O)NH(C 2-6 ynyl group), -C(O)NH(C 3-15 cycloalkyl), -C(O)NH (heterocyclic), -C(O)NH (C 6-10 aryl), -C(O)NH (heteroaryl), -C(O)N(C 1-9 alkyl) 2. -C(O)N(C 1-8 (haloalkyl) 2. -C(O)N(C 2-6 alkenyl) 2. -C(O)N(C 2-6 (alkynyl group) 2. -C(O)N(C 3-15 cycloalkyl) 2. -C(O)N (heterocyclic group) 2. -C(O)N(C 6-10 Aryl) 2. -C(O)N (Heteroaryl) 2. -NHC(O)(C 1-9 Alkyl), -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 2-6 alkenyl), -NHC(O)(C 2-6 ynyl group), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (C 6-10 aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 alkenyl), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (C 6-10 aryl), -NHC(O)O(heteroaryl), -NHC(O)NH(C 1-9 alkyl), -NHC(O)NH(C 1-8 Halogenated groups), -NHC(O)NH(C 2-6 alkenyl), -NHC(O)NH(C 2-6), -NHC(O)NH(C 3-15 cycloalkyl), -NHC(O)NH (heterocyclic), -NHC(O)NH (C 6-10 aryl), -NHC(O)NH (heteroaryl), -NHS(O)(C 1-9 alkyl), -N(C) 1-9 Alkyl)(S(O)(C) 1-9 alkyl), -S(C 1-9 alkyl), -S(C 1-8 Halogenated groups), -S(C 2-6 alkenyl), -S(C 2-6 alkynyl group), -S(C 3-15 cycloalkyl), -S (heterocyclic), -S (C 6-10 aryl), -S(heteroaryl), -S(O)N(C 1-9 alkyl) 2. -S(O)(C 1-9 Alkyl), -S(O)(C 1-8 Halogenated groups), -S(O)(C 2-6 alkenyl), -S(O)(C 2-6 ynyl group), -S(O)(C 3-15 cycloalkyl), -S(O)(heterocyclic), -S(O)(C 6-10 Aryl), -S(O) (heteroaryl), -S(O) 2(C 1-9 Alkyl groups), -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 2-6 alkenyl), -S(O) 2(C 2-6Alkyne group), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(C 6-10 Aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups), -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2; where Z 1b The alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally have one to three carbon atoms. 1-9 Alkyl, C 1-8 Halogenated groups, halogens, -OH, -NH 2. -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 3-15 cycloalkyl), -O (heterocyclic), -O (aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 3-15 cycloalkyl), -NH (heterocyclic), -NH (aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 3-15 cycloalkyl) 2. -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 3-15cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (aryl), -NHC(O)O (heteroaryl), -NHC(O)NH(C 1-9 Alkyl groups), S(O) 2(C 1-9 Alkyl groups), -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups), -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2 Replacement; Each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c Independent phylogenetic system - H, C 1-9 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Substitution; wherein, unless otherwise specified, the aryl groups of the compounds of formula (I) are C 6-10 Aryl; wherein, unless otherwise specified, each heteroaryl group of the compound of formula (I) is a 5- to 12-membered heteroaryl group having one to four heteroatoms of N, O, or S; wherein, unless otherwise specified, each heterocyclic group of the compound of formula (I) is a 3- to 20-membered heterocyclic group having one to four heteroatoms of N, O, or S. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H, -F, or -Cl; R 3 -H, -F, or -Cl; R 4aand R 4b Each can be independently of -H, halogen, -OH, or C. 1-6 Alkyl; Cyclic A-series C 3-10 Cycloalkyl or heterocyclic groups; n-series 0, 1, 2, 3, or 4; each R 5 Independent halogens, =O, -CN, C 1-6 Alkyl, C 1-6 Halogenated, C 1-6 Haloalkoxy, C 3-6 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, -O-(R) 51 ), or -N(R 51 (R) 52 ); where R 5 Each alkyl, cycloalkyl, alkoxy, haloalkyl, haloalkoxy, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different R groups. 5a Replace; Each R 5a Independent halogens, -CN, C 1-6 Alkyl, C 6-10 Aryl, or -O(R) 51 ); where each R can be the same or different 51 and R 52 Independent phylogenetic system - H, C 1-6 Alkyl, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, -C(O)N(R) 1a (R) 1b ), -S(O)(NR 1a (R) 1b -C(O)R 1c -S(O) 2)R 1c 、or -C(O)OR 1d , where R 6 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl-C(O)N(R) 2a (R) 2b ), -S(O)(NR 2a (R) 2b -C(O)R 2c S(O) 2)R 2c 、or -C(O)OR 2d , where R 7 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 20 heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, =O, imine, -NO 2. -N 3. -CN, -OR 3a -C(O)-R 3a -C(O)OR 3a -C(O)-N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + ,-N(R 3a )C(O)-R 3b -N(R) 3a )C(O)O-R 3b 、-N(R 3a )C(O)N(R 3b )(R 3c )、-N(R 3a )S(O) 2(R 3b )、-NR 3a S(O) 2N(R 3b )(R 3c )、-NR 3a S(O) 2O(R 3b )、-OC(O)R 3a 、-OC(O)OR 3a 、-OC(O)-N(R 3a )(R 3b )、-S-R 3a 、-S(O)R 3a 、-S(O)(NH)R 3a 、-S(O) 2R 3a 、-S(O) 2N(R 3a )(R 3b )、-S(O)(NR 3a )R 3b 、-S(O)(NR 3a )N(R 3b )(R 3c), -SF 5. or -Si(R) 3a ) 3; where each Z 1 Z 2 、or Z 3 The alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 芳基 , heteroaryl, =O, -NO 2. -CN, -N 3. -OR 3a -C(O)R 3a -C(O)OR 3a -C(O)N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + , -N(R 3a )(-C(O)R 3b , -N(R 3a )(-C(O)O(R 3b ), -N(R 3a )(-C(O)N(R 3b )(R 3c , -N(R 3a )(-S(O) 2(R 3b , -N(R 3a )(-S(O) 2-N(R 3b )(R 3c , -N(R 3a )(-S(O) 2O(R 3b ), -OC(O)R 3a , -OC(O)OR 3a , -OC(O)-N(R 3a )(R 3b , -S-R 3a , -S(O)R 3a , -S(O)(NH)R [[ID=<<MASK_BEGIN>>68]] 3a , 3a -S(O) 3a , -S(O) 2N(R [[ID=<<MASK_BEGIN>>78]] 3a )(R 3b ), -S(O)(NR 3a )(R [[ID=<<MASK_BEGIN>>88]] 3b , or -Si(R 3a ) 3; where Z 1a The alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, lateral oxygen, -OH, -CN, -NO 2. -NH 2. -N 3. -SH, -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 2-6 alkenyl), -O(C) 2-6 alkynyl group), -O(C 3-15 cycloalkyl), -O (heterocyclic), -O (C 6-10 aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 2-6 alkenyl), -NH (C 2-6 ynyl group), -NH(C 3-15 cycloalkyl), -NH (heterocyclic), -NH (C 6-10 aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 1-8 (haloalkyl) 2. -N(C 2-6 alkenyl) 2. -N(C 2-6 (alkynyl group) 2. -N(C 3-15 cycloalkyl) 2. -N (heterocyclic group) 2. -N(C 6-10 Aryl) 2. -N (Heteroaryl) 2. -N(C 1-9 Alkyl)(C 1-8 Halogenated groups), -N(C) 1-9 Alkyl)(C 2-6 alkenyl), -N(C) 1-9 Alkyl)(C 2-6 alkynyl group), -N(C 1-9 Alkyl)(C 3-15 cycloalkyl), -N(C) 1-9 Alkyl (heterocyclic), -N(C) 1-9 Alkyl)(C 6-10 aryl), -N(C 1-9 Alkyl)(heteroaryl), -C(O)(C 1-9 Alkyl), -C(O)(C 1-8 Halogenated groups), -C(O)(C 2-6 alkenyl), -C(O)(C 2-6 ynyl group), -C(O)(C 3-15 cycloalkyl), -C(O)(heterocyclic), -C(O)(C 6-10aryl), -C(O)(heteroaryl), -C(O)O(C 1-9 Alkyl), -C(O)O(C 1-8 Halogenated alkyl groups), -C(O)O(C 2-6 alkenyl), -C(O)O(C 2-6 alkynyl group), -C(O)O(C 3-15 cycloalkyl), -C(O)O (heterocyclic), -C(O)O (C 6-10 aryl), -C(O)O (heteroaryl), -C(O)NH 2. -C(O)NH(C) 1-9 Alkyl), -C(O)NH(C 1-8 Halogenated groups), -C(O)NH(C 2-6 alkenyl), -C(O)NH(C 2-6 ynyl group), -C(O)NH(C 3-15 cycloalkyl), -C(O)NH (heterocyclic), -C(O)NH (C 6-10 aryl), -C(O)NH (heteroaryl), -C(O)N(C 1-9 alkyl) 2. -C(O)N(C 1-8 (haloalkyl) 2. -C(O)N(C 2-6 alkenyl) 2. -C(O)N(C 2-6 (alkynyl group) 2. -C(O)N(C 3-15 cycloalkyl) 2. -C(O)N (heterocyclic group) 2. -C(O)N(C 6-10 Aryl) 2. -C(O)N (Heteroaryl) 2. -NHC(O)(C 1-9 Alkyl), -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 2-6 alkenyl), -NHC(O)(C 2-6 ynyl group), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (C 6-10 aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 alkenyl), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (C 6-10 aryl), -NHC(O)O(heteroaryl), -NHC(O)NH(C 1-9 alkyl), -NHC(O)NH(C 1-8 Halogenated groups), -NHC(O)NH(C 2-6 alkenyl), -NHC(O)NH(C 2-6 ), -NHC(O)NH(C 3-15 cycloalkyl), -NHC(O)NH (heterocyclic), -NHC(O)NH (C 6-10 aryl), -NHC(O)NH (heteroaryl), -NHS(O)(C 1-9 alkyl), -N(C) 1-9 Alkyl)(S(O)(C) 1-9 alkyl), -S(C 1-9 alkyl), -S(C 1-8Halogenated groups), -S(C 2-6 alkenyl), -S(C 2-6 alkynyl group), -S(C 3-15 cycloalkyl), -S (heterocyclic), -S (C 6-10 aryl), -S(heteroaryl), -S(O)N(C 1-9 alkyl) 2. -S(O)(C 1-9 Alkyl), -S(O)(C 1-8 Halogenated groups), -S(O)(C 2-6 alkenyl), -S(O)(C 2-6 ynyl group), -S(O)(C 3-15 cycloalkyl), -S(O)(heterocyclic), -S(O)(C 6-10 Aryl), -S(O) (heteroaryl), -S(O) 2(C 1-9 Alkyl groups), -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 2-6 alkenyl), -S(O) 2(C 2-6 Alkyne group), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(C 6-10 Aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups), -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2; where Z 1b The alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally have one to three carbon atoms. 1-9 Alkyl, C 1-8 Halogenated groups, halogens, -OH, -NH 2. -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 3-15 cycloalkyl), -O (heterocyclic), -O (aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 3-15 cycloalkyl), -NH (heterocyclic), -NH (aryl), -NH (heteroaryl), -N (C 1-9 alkyl) 2. -N(C 3-15 cycloalkyl) 2. -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (aryl), -NHC(O)O (heteroaryl), -NHC(O)NH(C 1-9 Alkyl groups), S(O) 2(C 1-9Alkyl groups), -S(O) 2(C 1-8 Halogenated groups), -S(O) 2(C 3-15 cycloalkyl), -S(O) 2(heterocyclic group), -S(O) 2(aryl), -S(O) 2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl groups), -S(O) 2NH(C 1-9 Alkyl), or -S(O) 2N(C 1-9 alkyl) 2 Replacement; Each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c Independent phylogenetic system - H, C 1-9 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein each R 1a R 1b R 1c R 1dR 2a R 2b R 2c R 2d R 3a R 3b and R 3c The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Substitution; wherein, unless otherwise specified, each heteroaryl group of the compound of formula (I) has one to four 5 to 12 heteroaryl groups, each independently of a heteroatom of N, O, or S; wherein, unless otherwise specified, each heterocyclic group of the compound of formula (I) has one to four 3 to 20 heterocyclic groups, each independently of a heteroatom of N, O, or S. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H or -F; R 21 System-H; R 3 -H or -F; R 4a and R 4b Each is independently associated with -H, -F, or -CH 3; Cyclopentyl, cyclohexyl, cycloheptyl, cyclohexenyl, or tetrahydropiperanyl rings of the A-series; n-series: 0, 1, or 2; Each R 5 Independent series -F, -OH, -CH 3. =CH 2. -CH 2-OH or -O-CH 3; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 6 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 7 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 12-membered heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, =O, -CN, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a ; among which each Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, -CN, -OR 3a 、or -S(O) 2R 3a Z 1a Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -CN, where Z 1b Each alkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is unsubstituted; each R 3a Independent phylogenetic system - H, C 1-9 Alkyl, C 6-10 aryl or heteroaryl, wherein R 3a Each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one to four 5 to 12 heteroaryl groups, each independently of a heteroatom of N, O, or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one to four 3 to 20 heterocyclic groups, each independently of a heteroatom of N, O, or S. In some embodiments of compounds of formula (I) or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H or -F; R 21 -H or -F; R 3 -H or -F; R 4a -H, -F, or -CH 3, and R 4b System-H; Ring A system , , , , , ,or n is 0, 1, or 2; each R 5 Independent series -F, -OH, -CH 3. =CH 2. -CH 2-OH or -O-CH 3; R 6 System-H or optionally via a Z 1 Replacement C 1-6 Alkyl, wherein Z 1 It has not been replaced; R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10 aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic system has a 3- to 7-membered heterocyclic group with an additional N; each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, O, and C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-15 cycloalkyl, C 6-10 aryl, heterocyclic, heteroaryl, or -OR 3a Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl groups, halogens, -CN, or -S(O) 2R 3a Z 1a Each alkyl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent halogens, C 3-15 cycloalkyl, or C 6-10 Aryl, of which Z 1b Each cycloalkyl or aryl group is unsubstituted; each R 3a Independent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one or two 5- to 6-membered heteroaryl groups, each independently of a heteroatom of N or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one or two 3- to 7-membered heterocyclic groups, each independently of a heteroatom of N or O. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (Ia), (Ia) or its medically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (Ib), (Ib) or its medically acceptable salt. In some embodiments of compounds of formula (I), formula (Ia), or formula (Ib), or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a and R 4b Each is independently associated with -H, -F, or -CH 3; Cyclopentyl, cyclohexyl, cycloheptyl, cyclohexenyl, or tetrahydropiperanyl rings of the A-series; n-series: 0, 1, or 2; Each R 5 Independent series -F, -OH, -CH 3. =CH 2. -CH 2-OH or -O-CH 3; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 6 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 7 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 12-membered heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, =O, -CN, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a ; among which each Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, -CN, -OR 3a 、or -S(O) 2R 3a Z 1a Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -CN, where Z 1b Each alkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is unsubstituted; each R 3a Independent phylogenetic system - H, C 1-9 Alkyl, C 6-10 aryl or heteroaryl, wherein R 3a Each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one to four 5 to 12 heteroaryl groups, each independently of a heteroatom of N, O, or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one to four 3 to 20 heterocyclic groups, each independently of a heteroatom of N, O, or S. In some embodiments of compounds of formula (I), formula (Ia), or formula (Ib), or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a and R 4b Each is independently associated with -H, -F, or -CH 3; Cyclopentyl, cyclohexyl, cyclohexenyl, or tetrahydropiperanyl rings of the A-series; n-series: 0, 1, or 2; Each R 5 Independent series -F, -OH, -CH 3. or -O-CH 3; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 6 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 7 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 12-membered heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, =O, -CN, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a ; among which each Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, -CN, -OR 3a 、or -S(O) 2R 3a Z 1a Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -CN, where Z 1b Each alkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is unsubstituted; each R 3a Independent phylogenetic system - H, C 1-9 Alkyl, C 6-10 aryl or heteroaryl, wherein R 3a Each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one to four 5 to 12 heteroaryl groups, each independently of a heteroatom of N, O, or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one to four 3 to 20 heterocyclic groups, each independently of a heteroatom of N, O, or S. In some embodiments, in a compound of formula (I), formula (Ia), or formula (Ib), or a pharmaceutically acceptable salt thereof, R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a and R 4b Each independently belongs to the -H or -F group; cyclic A group: cyclohexyl, cyclohexenyl, or tetrahydropiperanyl ring; n group: 0; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 6 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 7 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7The resulting heterocyclic group system comprises 3 to 12-membered heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independent halogens, =O, -CN, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a ; among which each Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independent phyla - D, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10aryl, heteroaryl, -CN, -OR 3a 、or -S(O) 2R 3a Z 1a Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -CN, where Z 1b Each alkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is unsubstituted; each R 3a Independent phylogenetic system - H, C 1-9 Alkyl, C 6-10 aryl or heteroaryl, wherein R 3a Each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one to four 5 to 12 heteroaryl groups, each independently of a heteroatom of N, O, or S; and wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one to four 3 to 20 heterocyclic groups, each independently of a heteroatom of N, O, or S. In some embodiments of compounds of formula (I), formula (Ia), or formula (1b), or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H or -F; R 3-H or -F; R 4a -H, -F, or -CH 3, and R 4b System-H; Ring A system , , , , , ,or n is 0, 1, or 2; each R 5 Independent series -F, -OH, -CH 3. =CH 2. -CH 2-OH or -O-CH 3; R 6 System-H or optionally via a Z 1 Replacement C 1-6 Alkyl, wherein Z 1 It has not been replaced; R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10 aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7The resulting heterocyclic system has a 3- to 7-membered heterocyclic group with an additional N; each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, O, and C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-15 cycloalkyl, C 6-10 aryl, heterocyclic, heteroaryl, or -OR 3a Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl groups, halogens, -CN, or -S(O) 2R 3a Z 1a Each alkyl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent halogens, C 3-15 cycloalkyl, or C 6-10 Aryl, of which Z 1b Each cycloalkyl or aryl group is unsubstituted; each R 3aIndependent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one or two 5- to 6-membered heteroaryl groups, each independently of a heteroatom of N or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one or two 3- to 7-membered heterocyclic groups, each independently of a heteroatom of N or O. In some embodiments of compounds of formula (I), formula (Ia), or formula (Ib), or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a -H, -F, or -CH 3, and R 4b System-H; Ring A system , , , , ,or n is 0, 1, or 2; each R 5 Independent series -F, -OH, -CH 3. or -O-CH 3; R 6 System-H or optionally via a Z 1 Replacement C 1-6 Alkyl, wherein Z 1 It has not been replaced; R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic system has a 3- to 7-membered heterocyclic group with an additional N; each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, O, and C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-15 cycloalkyl, C 6-10 aryl, heterocyclic, heteroaryl, or -OR 3a Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl groups, halogens, -CN, or -S(O) 2R 3a Z 1a Each alkyl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent halogens, C 3-15 cycloalkyl, or C 6-10 Aryl, of which Z 1b Each cycloalkyl or aryl group is unsubstituted; each R 3a Independent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one or two 5- to 6-membered heteroaryl groups, each independently of a heteroatom of N or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one or two 3- to 7-membered heterocyclic groups, each independently of a heteroatom of N or O. In some embodiments of compounds of formula (I), formula (Ia), or formula (Ib), or their pharmaceutically acceptable salts, R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a and R 4b Each system - H; Ring A system , ,or ; n-series 0; R 6 System-H or optionally via a Z 1 Replacement C 1-6Alkyl, wherein Z 1 It has not been replaced; R 7 Series-H, C 1-6 Alkyl, C 3-10 cycloalkyl or heterocyclic groups, wherein R 7 Each alkyl, cycloalkyl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic system has a 3- to 7-membered heterocyclic group with an additional N; each Z 1 Z 2 、or Z 3 Independent halogens, =O, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a Z 1 Z 2 、or Z 3 Each alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl groups, halogens, -CN, or -S(O) 2R 3a Z 1a Each alkyl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent halogens, C 3-15 cycloalkyl, or C 6-10 Aryl; of which Z 1b Each cycloalkyl or aryl group is unsubstituted; each R 3a Independent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one or two 5- to 6-membered heteroaryl groups, each independently of a heteroatom of N or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one or two 3- to 7-membered heterocyclic groups, each independently of a heteroatom of N or O. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIa), (IIa) or a medicinally acceptable salt thereof. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIb), (IIb) or a medicinally acceptable salt thereof. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIc), (IIc) or its pharmaceutically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IId), (IId) or its pharmaceutically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIe), (IIe) or its medicinally acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIf), (IIf) or its medically acceptable salt. In some embodiments, compounds of formula (I) or pharmaceutically acceptable salts of formula (IIg), (IIg) or its medically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIh), (IIh) or its medically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIi), (IIi) or its pharmaceutically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIj), (IIj) or its pharmaceutically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIk), (IIk) or its medically acceptable salt. In some embodiments of compounds of formula (I), (Ia), (Ib), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 4b -F or -CH 3. In some embodiments of compounds of formula (I), (Ia), (Ib), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or their pharmaceutically acceptable salts, each R 5 Independent series -F, -OH, -CH 3. or -O-CH 3. In some embodiments of compounds of formula (I), (Ia), (Ib), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or their pharmaceutically acceptable salts, R 6 Series-H. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 6 C 1-6 Alkyl or C 1-6 Alkyl haloide. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 6 It is not replaced by C 1-6 Alkyl. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 6 Tie , , , , , , , , ,or In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 6 System-CH 3 or In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 7C 1-6 Alkyl or C 3-10 Cycloalkyl groups, each optionally oxidized by one or two halogens or Z 2 C 6-10 Aryl substitution. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), or (IIi), or pharmaceutically acceptable salts thereof, R 7 C 1-6 Alkyl or cyclohexyl, each optionally denoted by one or two -F or Z groups. 2 The phenyl substitution. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 7 Tie , , , , , , , , , , ,or In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 7 Tie , ,or In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), or (IIk), or pharmaceutically acceptable salts thereof, R 7 Tie , ,or . In some embodiments, compounds of formula (I) or (IIa), or pharmaceutically acceptable salts of formula (IIIa), are used. (IIIa) or a medicinally acceptable salt thereof. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIIa-1) thereof, are used. (IIIa-1) or its pharmaceutically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIIa-2) thereof, are used. (IIIa-2) or its pharmaceutically acceptable salt. In some embodiments, compounds of formula (I), or pharmaceutically acceptable salts of formula (IIIa-3) thereof, are used. (IIIa-3) In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or pharmaceutically acceptable salts thereof, R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10 aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to three identical or different Z groups. 2 Replacement, in which each Z 2 Independently related to deuterium, halogens, =O, -CN, C 1-8 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 cycloalkyl, C 6-10 aryl, 5 to 12 heteroaryl groups having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or -C(O)-R 3a , where R 3a -H or unsubstituted C 1-6 Alkyl, wherein Z 2 Each C 1-6 Alkyl groups are optionally derived from 1 to 3 Z-axis groups. 1a Replacement, in which each Z 1a Independent cyano or C 1-6 Alkoxy 。 In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or pharmaceutically acceptable salts thereof, R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10 aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to three identical or different Z groups. 2 Replacement, in which each Z 2 Independently related to deuterium, halogens, =O, -CN, C 1-8 Alkyl, C 1-8 Halogenated, C 1-6Alkoxy, C 1-6 Haloalkoxy, C 3-10 cycloalkyl, C 6-10 Aryl, or -C(O)-R 3a , where R 3a -H or unsubstituted C 1-6 Alkyl, wherein Z 2 Each C 1-6 Alkyl groups are optionally derived from 1 to 3 Z-axis groups. 1a Replacement, in which each Z 1a Independent cyano or C 1-6 Alkoxy 。 In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or pharmaceutically acceptable salts thereof, R 7 Series-H, C 1-6 Alkyl, C 3-12 Cycloalkyl, or a 4- to 12-membered heterocyclic group having a heteroatom selected from nitrogen and oxygen, wherein R 7 Each alkyl, cycloalkyl, or heterocyclic group may optionally be connected by one to three identical or different Z-groups. 2 Replacement, in which each Z 2 Independent halogens, =O, C 1-6 Alkyl, C 1-8 Halogenated, C 1-6 alkoxy group, or -C(O)-R 3a , where R 3a -H or unsubstituted C 1-6 alkyl 。 In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or pharmaceutically acceptable salts thereof, R 7 Series-H, C 1-8 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.3]hexyl, bicyclo[3.1.1]heptyl, spiro[3.3]heptyl, spiro[2.5]octyl, oxetanyl, oxygen oxepanyl, di Alkyl, oxaspiro[3.3]heptyl, oxaspiro[3.5]nonyl, oxabicyclo[3.2.1]octyl, (3aR,6aS)-hexahydro-1H-cyclopenta[c]furanyl, bicyclo[3.2.1]octyl, (1R,5S)bicyclo[3.1.0]hexyl, (1R,5S)bicyclo[3.2.0]heptyl, (3aR,6aS)-2-methyloctahydropentadenyl ((3aR,6aS)-2-methyloctahydropentadenyl), (1R,5S)-6,6-dimethylbicyclo[3.1.0]hexyl, spiro[2.4]heptyl, 7,7-difluoro-spiro[3.5]nonyl, (4s,7s)-1-oxaspiro[3.5]nonyl, (4r,7r)-oxaspiro[3.5]nonyl, oxabicyclo[2.2.1]heptyl, 3-oxabicyclo[3.2.1]octyl, tetrahydrofuranyl, tetrahydropiperanyl, piperidinyl, tetrahydrothiaranyl, -2,3-dihydro-1H-indyl Chromane, or 4,5,6,7-tetrahydro-1H-indazole, each optionally fused with one to three identical or different Z-terminal groups. 2 Replacement, in which each Z 2 Independently related to deuterium, =O, -CN, -CH 3. -CH 2-O-CH 3. -CH 2-CN, -O-CH 3. -O-CF 3. -CF 3. -OC 2H 5. -OC 3H 7. -C(O)-CH 3. -F, cyclopropyl, phenyl, triazolyl, or pyridyl. In some examples of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or pharmaceutically acceptable salts thereof, R 7 is-H, C 1-8 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.3]hexyl, bicyclo[3.1.1]heptyl, spiro[3.3]heptyl, spiro[2.5]octyl, oxo-dopedyl, oxo Basic, Second Alkyl, oxaspiro[3.3]heptyl, oxaspiro[3.5]nonyl, oxabicyclo[3.2.1]octyl, (3aR,6aS)-hexahydro-1H-cyclopenta[c]furanyl, bicyclo[3.2.1]octyl, (1R,5S)bicyclo[3.1.0]hexyl, (1R,5S)bicyclo[3.2.0]heptyl, (3aR,6aS)-2-methyloctahydrocyclopentadiene, (1R,5S)-6,6-di Methylbicyclo[3.1.0]hexyl, spiro[2.4]heptyl, 7,7-difluoro-spiro[3.5]nonyl, (4s,7s)-1-oxaspiro[3.5]nonyl, (4r,7r)-oxaspiro[3.5]nonyl, oxabicyclo[2.2.1]heptyl, 3-oxabicyclo[3.2.1]octyl, tetrahydrofuranyl, tetrahydropiperanyl, piperidinyl, tetrahydrothiaranyl, 2,3-dihydro-1H-indenyl, , or 4,5,6,7-tetrahydro-1H-indazole, each optionally via 1 to 3 identical or different Z groups 2 Replacement, in which each Z 2 Independently related to deuterium, =O, -CN, -CH 3. -CH 2-O-CH 3. -CH 2-CN, -O-CH 3. -O-CF 3. -CF 3. -OC 2H 5. -OC 3H 7. -C(O)-CH 3. -F, cyclopropyl, or phenyl. In some examples of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or pharmaceutically acceptable salts thereof, R 7 Series-H, C 1-6 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[2.3]hexyl, bicyclo[3.1.1]heptyl, spiro[3.3]heptyl, spiro[2.5]octyl, oxalyl, oxaspiro[3.3]heptyl, oxaspiro[3.5]nonyl, oxabicyclo[3.2.1]octyl, tetrahydrofuranyl, tetrahydropiperanyl, piperidinyl, or tetrahydrothiaranyl, each optionally derived from 1 to 3 identical or different Z-terminal groups. 2 Replacement, in which each Z 2 Independent geosystems = O, -CH 3. -CF 3. -OC 2H 5. -C(O)-CH 3. or -F. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or pharmaceutically acceptable salts thereof, R 7 Series-H , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , ,or In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or their pharmaceutically acceptable salts, R 7 Series-H , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), or (IIIa-3), or their pharmaceutically acceptable salts, R 7 H, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or . In some embodiments, compounds of formula (I), (IIa), (IId), or (IIIa), or a pharmaceutically acceptable salt of formula (IVa), are used. (IVa) where q is 1, 2, or 3, or a medicinally acceptable salt thereof. In some embodiments of the compound of formula (IVa) or a pharmaceutically acceptable salt thereof, q refers to 1 or 2. In some embodiments of the compound of formula (IVa) or a pharmaceutically acceptable salt thereof, q refers to 1. In some embodiments, compounds of formula (I), (IIa), (IId), (IIIa), or (IVa), or their pharmaceutically acceptable salt series (IVa-1), are used. (IVa-1) or its pharmaceutically acceptable salt. In some embodiments, compounds of formula (I), (IIa), (IId), (IIIa), or (IVa), or their pharmaceutically acceptable salt formulation (IVa-2), are used. (IVa-2) or its pharmaceutically acceptable salt. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, Z 2 System-OR 3a C 3-15Cycloalkyl groups, 4- to 14-membered heterocyclic groups having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, C 6-10 aryl, 5 to 14 heteroaryl groups having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein each Z 2 Optionally, one to four Z-shaped points, which may be the same or different, can be used. 1a Replacement, in which each Z 1a Independently related to deuterium, cyano, halogen, and C 1-6 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl group, or -S(O) 2R 3a And each of them has R 3a Independent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be substituted with one to four halogens. In some examples of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, Z 2 System-OR 3a Cyclopropyl, cyclobutyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, oxalyl, tetrahydrofuranyl, tetrahydropiperanyl, 1,3-dioxacyclopentyl, phenyl, naphthyl, thiazolyl, pyrazolyl, pyridinyl, or pyridyl Each base can be optionally accessed via 1 or 3 Z-bases. 1a Replacement, in which each Z 1a Independently related to cyano, -F, -Cl, -OCH 3. -CF 3. or phenyl, wherein each R 3a Independently methyl, ethyl, or phenyl, wherein R 3a Each phenyl group may optionally be substituted with -Cl. In some examples of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, Z 2 System-OR 3a Cyclopropyl, cyclobutyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, oxalyl, tetrahydrofuranyl, tetrahydropiperanyl, 1,3-dioxacyclopentyl, phenyl, naphthyl, thiazolyl, pyrazolyl, pyridinyl, or pyridyl Each base can be optionally accessed via 1 or 2 Z-bases. 1a Replacement, in which each Z 1a Independently related to cyano, -F, -Cl, -OCH 3. -CF 3, and each of R 3a Independently methyl, ethyl, or phenyl, wherein R 3a Each phenyl group may optionally be substituted with -Cl. In some examples of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, Z 2 Tie , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or . In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), (IVa), (IVa-1), or (IVa-2), or their pharmaceutically acceptable salts, Z 2 It , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or . In some embodiments, compounds of formula (I), (IIa), (IId), or (IIIa), or their pharmaceutically acceptable salt formulation (IVb), are used. (IVb) where each Z 2 They may be the same or different, or they may be medicinally acceptable salts. In some embodiments of compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), or (IVb), or pharmaceutically acceptable salts thereof, the same or different Z may be used. 2 Independent system C 1-6 Alkyl, C 3-15 Cycloalkyl groups, 4- to 14-membered heterocyclic groups having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, C 6-14 Aryl, or C 1-6 Alkoxy groups, each optionally via 1 or 3 Z-terminal groups 1a Replacement, in which each Z 1a Independently related to halogens, cyano groups, =O, and C 1-6 Halogenated, C 3-10 cycloalkyl, or C 6-14 Aryl 。In some embodiments of compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), or (IVb), or pharmaceutically acceptable salts thereof, the same or different Z may be used. 2 Independent system C 1-6 Alkyl, C 3-15 Cycloalkyl groups, 4- to 14-membered heterocyclic groups having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, C 6-14 Aryl, or C 1-6 Alkoxy groups, each optionally via 1 or 3 Z-terminal groups 1a Replacement, in which each Z 1a Independently related halogen, cyano, C 1-6 Halogenated, C 3-10 cycloalkyl, C 6-14 Aryl 。 In some embodiments of compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), or (IVb), or pharmaceutically acceptable salts thereof, the same or different Z may be used. 2 Independent system C 1-6 Alkyl, C 3-15 cycloalkyl, C 6-14 Aryl, or C 1-6 Alkyl groups. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), or (IVb), or pharmaceutically acceptable salts thereof, the same or different Z may be present. 2Independently derived from methyl, ethyl, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropiperanyl, bicyclo[1.1.1]pentyl, phenyl, or thiaranyl, each optionally derived from 1 or 3 Z-terminal groups. 1a Replacement, in which each Z 1a Independent phylogenetic systems -F, -CH 3. -CHF 2. -CN, =O, or cyclopropyl. In some examples of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), or (IVb), or pharmaceutically acceptable salts thereof, the same or different Z may be present. 2 Independently, it is methyl, ethyl, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropiperanyl, bicyclo[1.1.1]pentyl, or phenyl, each optionally esterified by one or three Z-terminal groups. 1a Replacement, in which each Z 1a Independent phylogenetic systems -F, -CH 3. -CHF 2. -CN, or cyclopropyl. In some examples of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), or (IVb), or their pharmaceutically acceptable salts, the same or different Z may be present. 2 Independent geography - CH 3. -C 2H 5. , , , , , , , , , , , , , , , ,or . In some embodiments of compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), or (IVb), or pharmaceutically acceptable salts thereof, the same or different Z may be used. 2 Independent geography - CH 3. -C 2H 5. , , , , , , , , , , , , , , ,or In some embodiments of compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIa), or (IVb), or their pharmaceutically acceptable salts, the same or different Z may be used. 2 Independent geography - CH 3. , , ,or . In some embodiments, compounds of formula (I), (IIa), or (IId), or pharmaceutically acceptable salts of formula (IIIb), are used. (IIIb) Each of the p or q, which may be the same or different, is independently 1, 2, or 3, or a medicinally acceptable salt thereof. In some embodiments of the compound of formula (IIIb) or its pharmaceutically acceptable salt, p and q are each 1. In some embodiments of the compound of formula (IIIb) or its pharmaceutically acceptable salt, the same or different Z may be used. 1 or Z 2Independent phylogenetic system - H, C 6-10 Aryl, or a 4- to 10-membered heterocyclic group having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein Z 1 or Z 2 Each aryl or heterocyclic group is unsubstituted. In some embodiments of compounds of formula (IIIb) or their pharmaceutically acceptable salts, the same or different Z groups may be present. 1 or Z 2 Independently hydrogenated, unsubstituted phenyl, or unsubstituted tetrahydropiperanyl. In some embodiments of compounds of formula (IIIb) or their pharmaceutically acceptable salts, the same or different Z may be present. 1 or Z 2 Independent system , ,or . In some embodiments, compounds of formula (I), (IIa), or (IId), or pharmaceutically acceptable salts of formula (IIIc), are used. (IIIc) or its pharmaceutically acceptable salt. In some embodiments of compounds of formula (IIIc) or pharmaceutically acceptable salts thereof, Z 3 Series-H, C 6-10 aryl, or -OR 3a , where R 3a Series-H, C 1-6 Alkyl, or C 6-10 Aryl, wherein the R 3a Alkyl or aryl groups are each optionally halogenated, C 3-10 cycloalkyl, or C 6-10 Aryl substitution. In some embodiments of compounds of formula (IIIc) or their pharmaceutically acceptable salts, Z 3 Methyl, phenyl, or -OR 3a , where R 3aIt is methyl, ethyl, or phenyl, wherein R 3a The methyl or phenyl group may optionally be substituted with -Cl, cyclopropyl, or phenyl groups. In some embodiments of compounds of formula (IIIc) or pharmaceutically acceptable salts thereof, Z 3 Tie , , , , ,or . In some embodiments, compounds of formula (I), (IIa), or (IId), or pharmaceutically acceptable salts of formula (IIId), are used. (IIId) or its medically acceptable salt. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIId), or pharmaceutically acceptable salts thereof, Z 3 System can be selected via Z 1a One of the Cs 6-10 aryl-substituted C 1-6 Alkyl, wherein Z 1a The C 6-10 Aryl optional Z 1b One of the halogen substitutions. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIId), or their pharmaceutically acceptable salts, Z 3 System can be selected via Z 1a One of the phenyl-substituted methyl groups, wherein Z 1a The phenyl group can be optionally subjected to Z 1bOne of the -Cl substitutions. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIId), or pharmaceutically acceptable salts thereof, Z 3 Tie . In some embodiments, compounds of formula (I) or (IIa), or pharmaceutically acceptable salts of formula (IIIe), (IIIe) or its medicinally acceptable salt. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIe), or pharmaceutically acceptable salts thereof, R 7 C 1-6 Alkyl group. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIe), or pharmaceutically acceptable salts thereof, R 7 Tie . In some embodiments, compounds of formula (I), (IIc), or (IIf), or pharmaceutically acceptable salts of formula (IIIf), may be used. (IIIf) or its medically acceptable salt. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIf), or pharmaceutically acceptable salts thereof, R 7 C 1-8 Alkyl, C 3-12 Cycloalkyl, or a 4- to 12-membered heterocyclic group having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, or heterocyclic group may optionally be connected by one to three identical or different Z-groups. 2Replacement, in which each Z 2 Independently related to deuterium, halogens, and carbon 3-10 cycloalkyl, C 1-8 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, or a 4- to 12-membered heterocyclic group having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Z 2 Each C 1-6 Alkyl groups can optionally be 3 Z-shaped. 1a Replace 1, where each Z 1a Independent halogen or C 1-6 Alkoxy 。 In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIf), or pharmaceutically acceptable salts thereof, R 7 C 1-8 Alkyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, tetrahydrofuranyl, tetrahydropiperanyl, oxygen The group may be methyl, piperidinyl, or tetrahydroindazole, each optionally fused with one to three identical or different Z groups. 2 Replacement, in which each Z 2 Independently related to deuterium, -F, -CH 3. -CHF 2. -CH 2-CHF 2. -CF 3. CH 2-CF 3. -O-CH 3. -O-CHF 2. -CH 2-O-CH 3. -OC 3H 7. Cyclobutyl, oxo-1, or tetrahydropiperanyl, wherein each cyclobutyl, oxo-1, or tetrahydropiperanyl group is optionally substituted with 1 to 3 -F groups. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIf), or pharmaceutically acceptable salts thereof, R 7 C 1-8 Alkyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[3.3]heptyl, spiro[3.5]nonyl, tetrahydrofuranyl, tetrahydropiperanyl, oxygen The group, or piperidinyl group, each optionally fused with one to three identical or different Z groups. 2 Replacement, in which each Z 2 Independently related to deuterium, -F, -CH 3. -CHF 2. -CH 2-CHF 2. -CF 3. CH 2-CF 3. -O-CH 3. -O-CHF 2. -CH 2-O-CH 3. -OC 3H 7. Cyclobutyl, oxo-1, or tetrahydropiperanyl, wherein each cyclobutyl, oxo-1, or tetrahydropiperanyl group is optionally substituted with 1 to 3 -F groups. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIf), or pharmaceutically acceptable salts thereof, R 7 C can be optionally substituted with 1 to 3 halogens. 3-12 Cycloalkyl. In some examples of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIf), or pharmaceutically acceptable salts thereof, R 7 It is a cyclohexyl group optionally substituted with 1 to 3 -F groups. In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIf), or pharmaceutically acceptable salts thereof, R 7 Tie , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIf), or their pharmaceutically acceptable salts, R 7 Tie , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or In some embodiments of compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), or (IIIf), or their pharmaceutically acceptable salts, R 7 Tie or . In some embodiments of compounds of formula (I), (Ia), or (IIa), or their pharmaceutically acceptable salts, R 1 System-D. In some embodiments of compounds of formula (I), (Ia), (IIb), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, R 2 The series is -H or -F. In some embodiments of compounds of formula (I), (Ia), (IIb), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, R 2 System-H. In some embodiments of compounds of formula (I), (Ia), (IIb), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, R 2System-F. In some embodiments of compounds of formula (I), (Ia), (IIb), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, R 3 The series is -H or -F. In some embodiments of compounds of formula (I), (Ia), (IIb), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, R 3 System-H. In some embodiments of compounds of formula (I), (Ia), (IIb), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), or (IVa-2), or pharmaceutically acceptable salts thereof, R 3 -F. In some embodiments of compounds of formula (I), (Ia), (Ib), (IId), (IIe), (IIf), (IIg), (IIh), or (IIi), or pharmaceutically acceptable salts thereof, R 4a and R 4b Each department - H. In some embodiments, a compound of formula (I) or a pharmaceutically acceptable salt of formula (V) thereof (V) or its pharmaceutically acceptable salt, wherein R 2 -H or -F; R 21 -H or -F; R 3 -H or -F; R 7 C 1-8 Alkyl or C 3-12 cycloalkyl, wherein R 7 Each alkyl or cycloalkyl group may optionally be derived from one to four identical or different Z groups. 2 Replacement; and each Z 2 Independently related to deuterium, halogens, and carbon 1-3 Alkyl, C 1-3 Halogenated, or C 6-10 Aryl. In some embodiments, compounds of formula (V), or pharmaceutically acceptable salts of formula (Va) thereof: (Va) or its medically acceptable salt. In some embodiments of compounds of formula (V) or (Va), or pharmaceutically acceptable salts thereof, R 2 System-H;R 2a System -H; and R 3 The series is -H or -F. In some embodiments of compounds of formula (V) or (Va), or pharmaceutically acceptable salts thereof, R 7 C 1-8 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.3]hexyl, bicyclo[3.1.1]heptyl, spiro[3.3]heptyl, spiro[2.5]octyl, bicyclo[3.2.1]octyl, (1R,5S)bicyclo[3.1.0]hexyl, (1R,5S)bicyclo[3.2.0]heptyl, spiro[2.4]heptyl, each optionally via 1 to 3 Z-terms that may be identical or different 2 Replacement, in which each Z 2 Independently connected to deuterium, -CH 3. -C 2F, -CHF 2. -CF 3. -F, or phenyl. In some embodiments of compounds of formula (V) or (Va), or pharmaceutically acceptable salts thereof, R 7 C 1-3 Alkyl or cyclohexyl groups, each optionally fused with one or two identical or different Z groups. 2 Replacement, in which each Z 2 Independently -F or phenyl. In some embodiments of compounds of formula (V) or (Va), or pharmaceutically acceptable salts thereof, R 7 Tie , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or In some embodiments of compounds of formula (V) or (Va), or pharmaceutically acceptable salts thereof, R 7 Tie , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or . In some embodiments, the compound of formula (V) or its pharmaceutically acceptable salt system , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or Or a medically acceptable salt. In some embodiments, the compound of formula (V), or its pharmaceutically acceptable salt, is... , , , , , , , , , , , , ,or Or a medically acceptable salt. In some embodiments, compounds of formula (I) or pharmaceutically acceptable salts of formula (VI) are used. (VI) or its pharmaceutically acceptable salt, wherein R 7 The system can be optionally connected via one to four Z-shaped nodes, which may be the same or different. 2 Replacement C 3-12 cycloalkyl groups; and each Z 2 Independently related to deuterium, halogens, and carbon 1-3 Alkyl, C 1-3 Halogenated groups. In some embodiments, compounds of formula (VI), or pharmaceutically acceptable salts of formula (VIa) thereof: (VIa) or its medically acceptable salt. In some embodiments of compounds of formula (VI) or (VIa), or pharmaceutically acceptable salts thereof, R 7 The system can be optionally connected via 1 to 4 Z-type nodes, which may be the same or different. 2 Substituted cyclohexyl groups, wherein each Z 2 Independently connected to deuterium, -CH 3. -C 2F, -CHF 2. -CF 3, or -F. In some embodiments, In some embodiments, the compound of formula (VI), or its pharmaceutically acceptable salt system, , , , , , , , , , , , , , , , , , , , , ,or Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (VI), or its pharmaceutically acceptable salt system, , , , , , , , , , ,or Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or , or a medically acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or Or a medically acceptable salt. In some embodiments, compounds of formula (I) or (IId), or their pharmaceutically acceptable salts, are used. , , , , , , , , , , , , ,or Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (IIk), or (IIIa-1), or their pharmaceutically acceptable salts, are used. , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. , , , , , ,or Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. , , , , , ,or Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIb), or its pharmaceutically acceptable salt system, may be used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIc), or a pharmaceutically acceptable salt thereof, , ,or Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIc), or a pharmaceutically acceptable salt thereof, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIc), or a pharmaceutically acceptable salt thereof, , , , , , , , , , , , , ,or Or, or a medicinally acceptable salt. In some embodiments, a compound of formula (I) or (IIg), or a pharmaceutically acceptable salt thereof, may be used. Or, or a medicinally acceptable salt. In some embodiments, a compound of formula (I) or (IIh), or a pharmaceutically acceptable salt thereof, may be used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIi), or a pharmaceutically acceptable salt thereof, Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIj), or its pharmaceutically acceptable salt system, may be used. Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I) or (IIk), or their pharmaceutically acceptable salts, Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (Ia), or (IIa), or their pharmaceutically acceptable salts, Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (Ib), or (IIa), or their pharmaceutically acceptable salts, are used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, the compound of formula (I) or (IIa), or a pharmaceutically acceptable salt thereof, is used. Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (Ia), or (IIc), or their pharmaceutically acceptable salts, Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (Ib), or (IIc), or their pharmaceutically acceptable salts, may be used. Or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (Ia), or (IIc), or their pharmaceutically acceptable salts, Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (Ib), or (IIc), or their pharmaceutically acceptable salts, may be used. Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (Ia), or (IIc), or their pharmaceutically acceptable salts, Or, or a medicinally acceptable salt. In some embodiments, compounds of formula (I), (Ib), or (IIc), or their pharmaceutically acceptable salts, may be used. Or, or a medicinally acceptable salt. In some embodiments, this disclosure provides racemic mixtures comprising compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof. In some embodiments, this disclosure provides racemic compounds comprising compounds disclosed herein or pharmaceutically acceptable salts thereof. In some embodiments, this disclosure provides non-racemic mixtures comprising compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof. In some embodiments, this disclosure provides non-racemic compounds comprising compounds disclosed herein or pharmaceutically acceptable salts thereof. Those skilled in the art will understand that the groups disclosed herein (e.g., R) 1 Each embodiment of the above can be combined with each of the remaining groups (e.g., R). 2 R 3 Z 1 Z 2 Any other combination of embodiments of formula (I) or any formula described herein to produce a compound or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, is considered to be within the scope of the invention. Pharmaceutical components and delivery models In addition, this disclosure provides pharmaceutical compositions comprising at least one of the compounds disclosed herein, or a prodrug compound thereof, or a pharmaceutically acceptable salt or solvate thereof, as an active ingredient and a pharmaceutically acceptable carrier. The pharmaceutical composition disclosed herein may additionally contain one or more other compounds as active ingredients, such as prodrug compounds or other enzyme inhibitors. The formulations are suitable for oral, rectal, topical, parenteral (including subcutaneous, intramuscular, and intravenous), ocular (ophthalmic), pulmonary (nasal or buccal inhalation), or nasal administration, but in any given case, the most appropriate route will depend on the nature and severity of the condition to be treated and the characteristics of the active ingredient. They may be suitably presented in unit dosage forms and prepared by any method known in the field of pharmaceutical technology. In practical applications, the compounds disclosed herein can be combined as active ingredients with pharmaceutical carriers in a close mixture using conventional pharmaceutical compounding techniques. The carrier can take various forms, depending on the intended dosage form (e.g., oral or parenteral (including intravenous)). In preparing compositions for oral dosage forms, any useful pharmaceutical medium can be used, such as water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like in the case of oral liquid dosage forms such as suspensions, elixirs, and solutions; or carriers, such as starch, sugars, microcrystalline cellulose, diluents, granulators, lubricants, binders, disintegrants, and the like in the case of oral solid dosage forms such as powders, hard and soft capsules, and tablets, wherein solid oral dosage forms are preferred over liquid dosage forms. Because tablets and capsules are easy to administer, they are the most advantageous forms of oral dosage units, employing a solid pharmaceutical carrier. Tablets can be coated using standard aqueous or non-aqueous techniques if desired. Such compositions and formulations should contain at least 0.1 percent of the active compound. The percentage of the active compound in these compositions can, of course, vary and can appropriately range from about 2 percent to about 60 percent by weight. In such therapeutically useful compositions, the amount of active compound achieves an effective dosage. The active compound can also be administered intranasally, for example, as drops or sprays. Tablets, pills, capsules, and the like may also contain binders such as gum arabic, gum arabic, corn starch, or gelatin; excipients such as dicalcium phosphate; disintegrants such as corn starch, potato starch, or alginic acid; lubricants such as magnesium stearate; and sweeteners such as sucrose, lactose, or saccharin. When the dosage unit is in capsule form, it may contain a liquid carrier, such as fatty oil, in addition to the materials of the above types. Various other materials may exist in the physical form of coatings or modified dosage units. For example, tablets may be coated with shellac, sugar, or both. Slurries or elixirs may contain, in addition to the active ingredient, sucrose as a sweetener, methyl and propylparabens as preservatives, dyes, and flavorings such as cherry or orange flavorings. In some embodiments, the compounds disclosed herein may also be used as salts of various relative cations to produce orally available formulations. The compounds disclosed herein can also be administered parenterally. Solutions or suspensions of these active compounds can be suitably prepared by mixing them with surfactants such as hydroxypropyl cellulose in water. Dispersions can also be prepared in oils with glycerol, liquid polyethylene glycol, and mixtures thereof. Under normal storage and use conditions, these formulations contain preservatives to prevent microbial growth. Pharmaceutical formulations suitable for injection include sterile aqueous solutions or dispersions and sterile powders for the immediate preparation of sterile injectable solutions or dispersions. In all cases, the formulation must be sterile and must be a fluid in a readily injectable state. It must be stable under manufacturing and storage conditions and must be preserved in a manner that prevents contamination by microorganisms such as bacteria and fungi. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyols (e.g., glycerol, propylene glycol, liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils. The disclosed compounds can be administered via any suitable route to provide an effective dose for mammals, particularly humans. For example, they can be administered orally, rectally, topically, parenterally, ocularly, pulmonaryly, nasally, and similarly. Dosage forms include lozenges, sublingual tablets, dispersions, suspensions, solutions, capsules, creams, ointments, aerosols, and the like. In some embodiments, the disclosed compounds are administered orally. Set This document also provides kits comprising the disclosed compound, or a pharmaceutically acceptable salt, tautomer, stereoisomer, mixture of stereoisomers, prodrug, or deuterated analog, and suitable packaging. In one embodiment, the kit further includes instructions for use. In one embodiment, the kit includes the disclosed compound, or a pharmaceutically acceptable salt, tautomer, stereoisomer, mixture of stereoisomers, prodrug, or deuterated analog, and labeling and / or instructions for use of the compound in its therapeutic indications (including the diseases or conditions described herein). This article also provides an article comprising, in a suitable container, the compound described herein or a pharmaceutically acceptable salt, tautomer, stereoisomer, mixture of stereoisomers, prodrug, or deuterated analogue thereof. The container may be a vial, jar, ampoule, pre-loaded syringe, or intravenous bag. Treatment methods and uses The compounds provided herein, or their pharmaceutically acceptable salts, or compositions containing such compounds or their pharmaceutically acceptable salts, may be used for pharmaceutical purposes. In some embodiments, the compounds provided herein, or their pharmaceutically acceptable salts, or compositions containing such compounds or their pharmaceutically acceptable salts, are used to treat IKFZ2-related diseases or conditions. In some embodiments, the compounds provided herein, or their pharmaceutically acceptable salts, or compositions containing such compounds or their pharmaceutically acceptable salts, are used to treat cancer. In some embodiments, the compounds provided herein, or their pharmaceutically acceptable salts, or compositions containing such compounds or their pharmaceutically acceptable salts, may be used to manufacture agents for treating IKFZ2-related diseases or conditions. In some embodiments, the compounds provided herein, or their pharmaceutically acceptable salts, or compositions containing such compounds or their pharmaceutically acceptable salts, may be used to manufacture agents for treating cancer. This disclosure further relates to the use of the compounds disclosed herein or their pharmaceutically acceptable salts for the treatment and / or prevention of diseases and / or conditions by binding to and degrading IKZF proteins (e.g., IKZF2 or IKZF4 proteins) with the compounds. Additionally, this disclosure relates to the use of the compounds or their pharmaceutically acceptable salts for the preparation of medicaments for the treatment and / or prevention of IKZF-related diseases and / or conditions by binding to and degrading IKZF proteins (e.g., IKZF2 or IKZF4 proteins) with the compounds. In some embodiments, IKZF-related diseases or conditions are alleviated by selectively degrading IKZF2 proteins. In some embodiments, IKZF-related diseases or conditions are alleviated by degrading IKZF2 proteins. In some embodiments, IKZF-related diseases or conditions are alleviated by degrading IKZF2 proteins and one or more additional IKZF2 proteins (e.g., IKZF1 and / or IKZF4 proteins). In some embodiments, IKZF-related diseases or conditions are alleviated by degrading the IKZF4 protein. In some embodiments, IKZF-related diseases and / or conditions are IKZF2-related diseases and / or conditions. In some embodiments, IKZF2-related diseases or conditions are alleviated by selectively degrading the IKZF2 protein. In some embodiments, IKZF2-related diseases and / or conditions are alleviated by degrading the IKZF2 protein and one or more additional IKZF proteins (e.g., IKZF1 and / or IKZF4 proteins). As referred to herein, pharmaceutical preparations can be made by known procedures, including combinations of compounds disclosed herein with pharmaceutically acceptable carriers. In some embodiments, this document provides a method for treating and / or preventing IKZF protein (e.g., IKZF2 protein)-related diseases or conditions in patients with such need, comprising administering to the patient a therapeutically effective amount of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V) Compounds of (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, or compositions comprising compounds of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof. In some embodiments, this document provides a method for degrading IKZF proteins (e.g., IKZF2 protein), comprising administering to a patient in need (e.g., a patient with an IKZF protein-related disease or condition) a therapeutically effective amount of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2) Compounds of (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, or compositions comprising compounds of (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof. In some embodiments, this document provides a method for reducing cell proliferation and reducing the level of IKZF protein (e.g., IKZF2 protein) in cells, comprising contacting the cells with a compound of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or a pharmaceutically acceptable salt thereof. In some embodiments, this document provides a method for reducing IKFZ protein (e.g., IKZF2 protein) levels in patients with this need (e.g., patients with IKZF2-related diseases or conditions), comprising administering to the patient a therapeutically effective amount of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2) (I), (V), (Va), (VI), or (VIa), or a pharmaceutically acceptable salt thereof, or a composition comprising a compound containing (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or a pharmaceutically acceptable salt thereof. In some embodiments, diseases or conditions associated with IKZF proteins (e.g., IKZF2 protein) include cancer. In some embodiments, the cancer is a blood cancer. In some embodiments, the cancer includes a solid tumor. In some embodiments, the cancer includes a malignant tumor. In some embodiments, the cancer includes metastatic cancer. In some embodiments, the cancer is resistant or refractory to one or more anticancer therapies. In some embodiments, more than about 50% of the cancer cells detectably exhibit one or more cell surface immune checkpoint receptors (e.g., so-called "hot" cancer or tumor). In some embodiments, more than about 1% and less than about 50% of the cancer cells detectably exhibit one or more cell surface immune checkpoint receptors (e.g., so-called "warm" cancer or tumor). In some embodiments, less than about 1% of the cancer cells detectably exhibit one or more cell surface immune checkpoint receptors (e.g., so-called "cold" cancer or tumor). In some embodiments, IKZF protein (e.g., IKZF2 protein)-related diseases or conditions are blood cancers, such as leukemia (e.g., acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), B-cell ALL, myelodysplastic syndrome (MDS), myeloproliferative disorders (MPD), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), undifferentiated leukemia), lymphoma (e.g., small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), T-cell lymphoma, B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL), Waldestrom macroglobulinemia (WM)), and / or myeloma (e.g., multiple myeloma (MM)). In some embodiments, diseases or conditions associated with IKZF proteins (e.g., IKZF2 protein) are epithelial tumors (e.g., carcinoma, squamous cell carcinoma, basal cell carcinoma, squamous intraepithelial neoplasia), glandular tumors (e.g., adenocarcinoma, adenoma, adenomyoma), mesenchymal or soft tissue tumors (e.g., sarcoma, rhabdomyosarcoma, leiomyosarcoma, liposarcoma, fibrosarcoma, dermatofibrosarcoma, neurofibrosarcoma, fibrous histiocytoma, angiosarcoma, angiomyxoma, leiomyosarcoma, chondroma, chondrosarcoma, alveolar soft tissue sarcoma, epithelioid angioendothelioma, Spitz tumor, synovial sarcoma), or lymphoma. In some embodiments, IKZF protein-related diseases or conditions include solid tumors originating in or in tissues or organs such as: ● Bone (e.g., amelioma, aneurysmal bone cyst, angiosarcoma, chondrocyte blastoma, chondroma, chondromycinoid fibroma, chondrosarcoma, chordoma, dedifferentiated chondrosarcoma, enchondroma, epithelioid hemangioendothelioma, fibrous dysplasia of bone, giant cell tumor of bone, hemangioma and related lesions, osteoblastoma, osteochondroma, osteosarcoma, osteoid osteoma, osteoma, periosteal chondroma, desmoid tumor, Ewing's sarcoma); ● Lip and oral cavity (e.g., odontogenic ameloblastoma, oral leukoplakia, oral squamous cell carcinoma, primary oral mucosal melanoma); salivary glands (e.g., salivary gland pleomorphic adenoma, salivary gland adenoid cystic carcinoma, salivary gland mucoepidermoid carcinoma, salivary gland Warthin's tumor); ● Esophagus (e.g., Barrett's esophagus, dysplasia, and adenocarcinoma); ● Gastrointestinal tract, including the stomach (e.g., gastric adenocarcinoma, primary gastric lymphoma, gastrointestinal stromal tumor (GIST), metastatic deposits, gastric carcinoid, gastric sarcoma, neuroendocrine carcinoma, primary squamous cell carcinoma of the stomach, gastric adenoacanthoma), small intestine and smooth muscle (e.g., intravenous leiomyomatosis), colon (e.g., colorectal adenocarcinoma), rectum, anus; ● Pancreas (e.g., serous tumors, including small or large cystic serous cystadenomas, solid serous cystadenomas, Von Hippel-Landau...). (VHL) related serous cystic tumors, serous cystadenocarcinomas; mucinous cystic tumors (MCN), intraductal papillary mucinous tumors (IPMN), intraductal eosinophilic papillary tumors (IOPN), intraductal tubular tumors, cystic acinar tumors, including acinar cell cystadenomas, acinar cell cystadenocarcinomas, pancreatic cancer, invasive pancreatic duct adenocarcinomas, including tubular adenocarcinomas, adenosquamous carcinomas, colloid carcinomas, medullary carcinomas, hepatoid carcinomas, ring cell carcinomas, undifferentiated carcinomas, undifferentiated carcinomas with osteoclast-like giant cells, acinar cell carcinomas, neuroendocrine tumors, neuroendocrine microadenomas, neuroendocrine tumors (NET), neuroendocrine carcinomas (NEC), including small cell or large cell NEC, insulinomas, gastrinomas, glucagonomas, serotonin-producing NETs, ​​somatostatinomas, VIP tumors, solid pseudopapillary tumors (SPN), pancreatoblastomas); ● Gallbladder (e.g., gallbladder and extrahepatic bile duct carcinomas, intrahepatic bile duct carcinomas); ● Neuroendocrine (e.g., adrenocortical carcinoma, carcinoid tumor, pheochromocytoma, pituitary adenoma); ● Thyroid (e.g., degenerative (undifferentiated) carcinoma, medullary carcinoma, eosinophilic cell tumor, papillary carcinoma, adenocarcinoma); ● Liver (e.g., adenoma, combined hepatocellular and bile duct carcinoma, lamellar fibrous carcinoma, hepatoblastoma, hepatocellular carcinoma, mesenchymal, nested stromal epithelial tumors, undifferentiated carcinoma);Hepatocellular carcinoma, intrahepatic bile duct carcinoma, bile duct cystadenocarcinoma, epithelioid hemangioendothelioma, angiosarcoma, embryonal sarcoma, rhabdomyosarcoma, solitary fibrous tumor, teratoma, yolk sac tumor, carcinosarcoma, rhabdomyosarcoma; ● Kidney (e.g., ALK rearranged renal cell carcinoma, chromophobe renal cell carcinoma, clear cell renal cell carcinoma, clear cell sarcoma, metarenal adenoma, metarenal fibroma, mucinous tubular and spindle cell carcinoma, nephroma, Wilms' tumor, papillary adenoma, papillary renal cell carcinoma, renal eosinophilic cell tumor, renal cell carcinoma, succinate dehydrogenase-deficient renal cell carcinoma, collecting duct carcinoma); ● Breast (e.g., invasive ductal carcinoma, including but not limited to acinar cell carcinoma, adenoid cystic carcinoma, apocrine carcinoma, cribriform carcinoma, glycogen-rich / clear cell carcinoma, inflammatory carcinoma, lipid-rich carcinoma, medullary carcinoma, histiomorphic carcinoma, micropapillary carcinoma, mucinous carcinoma, neuroendocrine carcinoma, eosinophilic cell carcinoma, papillary carcinoma, sebaceous gland carcinoma, secretory breast carcinoma, tubular carcinoma; lobular carcinoma, including but not limited to pleomorphic carcinoma, ring cell carcinoma); ● Peritoneum (e.g., mesothelioma; primary peritoneal carcinoma); ● Female sex organ tissues, including ovaries (e.g., choriocarcinoma, epithelial tumors, germ cell tumors, sex cord-stromal tumors), fallopian tubes (e.g., serous adenocarcinoma, mucinous adenocarcinoma, endometrioid adenocarcinoma, clear cell adenocarcinoma, transitional cell carcinoma, squamous cell carcinoma, undifferentiated carcinoma, Müllerian tumor, adenosarcoma, leiomyosarcoma, teratoma, germ cell tumors, choriocarcinoma, trophoblastic tumors), uterus (e.g., cervical cancer, endometrial polyps, endometrial hyperplasia, intraepithelial carcinoma (EIC), endometrial cancer (e.g., endometrioid carcinoma, serous carcinoma, clear cell carcinoma, mucinous carcinoma, squamous cell carcinoma, transitional cell carcinoma, small cell carcinoma, undifferentiated carcinoma, mesenchymal tumors), leiomyomas (e.g., endometrial stromal nodules, leiomyosarcoma, endometrial stromal sarcoma (ESS), mesenchymal tumors), mixed epithelial and mesenchymal tumors (e.g., adenofibroma, carcinoma, adenosarcoma, carcinosarcoma (malignant mixed mesodermal sarcoma-)). Malignant Millais duct tumors (MMMT), endometrial stromal tumors, mixed malignant Millais duct tumors of the endometrium, gestational trophoblastic tumors (partial cystic ...● Eye (e.g., retinoma, retinoblastoma, ocular melanoma, posterior uveal melanoma, iris hamartoma); ● Head and neck (e.g., nasopharyngeal carcinoma, endolymphatic sac tumor (ELST), epidermoid carcinoma, laryngeal carcinoma including squamous cell carcinoma (SCC) (e.g., glottic carcinoma, supraglottic carcinoma, subglottic carcinoma, transglottic carcinoma), carcinoma in situ, verrucous, spindle cell and basaloid SCC, undifferentiated carcinoma, laryngeal adenocarcinoma, adenoid cystic carcinoma, neuroendocrine carcinoma, laryngeal sarcoma), head and neck paraganglioma (e.g., carotid body, cervical bone, vagus nerve); ● Thymus (e.g., thymoma); ● Heart (e.g., cardiac myxoma); ● Lung (e.g., small cell carcinoma (SCLC), non-small cell lung cancer (NSCLC), including squamous cell carcinoma (SCC), adenocarcinoma, and large cell carcinoma, carcinoid (typical or atypical), carcinosarcoma, pulmonary blastoma, giant cell carcinoma, spindle cell carcinoma, pleural pulmonary blastoma); ● Lymphomas (e.g., lymphomas including Hodgkin's lymphoma, non-Hodgkin's lymphoma (NHL), indolent non-Hodgkin's lymphoma (iNHL), refractory iNHL, Estée Chalamet virus (EBV)-associated lymphoproliferative disorders, including B-cell lymphomas and T-cell lymphomas (e.g., Burkitt's lymphoma; large B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, indolent B-cell lymphoma, low-grade B-cell lymphoma, fibrin-associated diffuse large cell lymphoma; primary exudative lymphoma; plasmablastic lymphoma; extranodal nasal NK / T-cell lymphoma; peripheral T-cell lymphoma, cutaneous T-cell lymphoma, angioimmunoepithelial T-cell lymphoma; follicular T-cell lymphoma; systemic T-cell lymphoma), lymphangioleiomyomatosis); ● Central nervous system (CNS) tumors (e.g., gliomas, including astrocytic tumors such as pilocytic astrocytoma, pilocytic myxoid astrocytoma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma, diffuse astrocytoma, fibrillary astrocytoma, obese astrocytoma, protoplasmic astrocytoma, degenerative astrocytoma, glioblastoma (e.g., giant cell glioblastoma, gliosarcoma, glioblastoma multiforme), and gliomatosis of the brain), oligodendritic gliomas (e.g., oligodendritic glioma, degenerative oligodendritic glioma). Gliomas, oligostellate cell tumors (e.g., oligostellate cell tumors, degenerative oligostellate cell tumors), ependymal tumors (e.g., subependymal tumors, myxopapillary ependymomas, ependymomas (e.g., cellular, papillary, clear cell, elongated cell types), degenerative ependymomas), optic nerve gliomas and non-gliomas (e.g., choroid plexus tumors, neuronal and mixed neuronal glial cell tumors, pineal region tumors, embryonal tumors, neuroblastomas, meningeal tumors, primary CNS lymphomas, germ cell tumors, pituitary adenomas, cranial and paravertebral nerve tumors, stellate region tumors);Neurofibromas, spinal meningiomas, peripheral nerve sheath tumors, peripheral neuroblastomas (including but not limited to neuroblastomas, ganglioblastomas, and gangliocytomas), ependymomas of chromosome 19 tris; ● Neuroendocrine tissues (e.g., the paraganglionic system, including adrenal medulla (pheochromocytoma) and extra-adrenal paragangliomas); ● Skin (e.g., clear cell hidradenoma, benign fibrous histiocytoma of the skin, cylindrica, hidradenoma, melanoma (including cutaneous melanoma and mucosal melanoma), trichomeoma, Spitz's tumor); and ● Soft tissue tumors (e.g., aggressive angiomyxoma, alveolar rhabdomyosarcoma, alveolar soft tissue sarcoma, angiofibroma, hemangioma-like fibrous histiocytoma, synovial sarcoma, biphasic synovial sarcoma, clear cell sarcoma, dermatofibrosarcoma protuberance, desmoid fibromatosis, small round cell tumor, connective tissue proliferative small round cell tumor, elastic fibroma, embryonal rhabdomyosarcoma, Ewing's tumor / primitive neuroectodermal tumor (PNET), extraosseous myxoid chondrosarcoma, extraosseous osteosarcoma, paravertebral tumors) Sarcoma, inflammatory myofibroblastic tumor, lipoblastoma, lipoma, chondromatous lipoma, liposarcoma / malignant lipomatous tumor, liposarcoma, myxoid liposarcoma, fibromyxoid sarcoma, lymphangioleiomyoma, malignant myoepithelioma, soft tissue malignant melanoma, myoepithelial carcinoma, myoepithelioma, myxoid inflammatory fibroblastic sarcoma, undifferentiated sarcoma, pericytoma, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), soft tissue leiomyosarcoma, undifferentiated sarcoma, well-differentiated liposarcoma. In some embodiments, the diseases or conditions associated with the IKZF protein (e.g., IKZF2 protein) are selected from cancers such as lung cancer, colorectal cancer, breast cancer, prostate cancer, cervical cancer, pancreatic cancer, and head and neck cancer. In some embodiments, the cancer is metastatic. In some embodiments, IKZF protein-related diseases or conditions (e.g., IKZF2 protein) are selected from cancers such as non-small cell lung cancer (NSCLC), melanoma, triple-negative breast cancer (TNBC), nasopharyngeal carcinoma (NPC), microsatellite stable colorectal cancer (mssCRC), thymoma, and gastrointestinal stromal tumor (GIST). In some embodiments, the cancer is metastatic. dose The effective dosage of the active ingredient used may vary depending on the specific compound used, the administration method, the condition to be treated, and the severity of the condition. Such dosages can be easily determined by those skilled in the art. When treating or preventing diseases or conditions related to the IKZF protein (e.g., IKZF2 protein) to which the disclosed compounds are applicable, generally satisfactory results are obtained when the disclosed compounds are administered at a daily dose of about 0.1 mg to about 300 mg per kilogram of animal body weight. In some embodiments, the disclosed compounds are administered in a single daily dose, or in two to six separate doses per day, or in a sustained-release form. For most large mammals, the total daily dose is about 1 mg to about 1000 mg, or about 1 mg to about 50 mg. For example, for a 70 kg adult, the total daily dose is typically about 0.1 mg to about 200 mg. This dosage regimen may be adjusted to provide the best therapeutic response. In some embodiments, the total daily dose is about 1 mg to about 900 mg, about 1 mg to about 800 mg, about 1 mg to about 700 mg, about 1 mg to about 600 mg, about 1 mg to about 400 mg, about 1 mg to about 300 mg, about 1 mg to about 200 mg, about 1 mg to about 100 mg, about 1 mg to about 50 mg, about 1 mg to about 20 mg, or about 1 mg to about 10 mg. The compounds or their components described in this application may be administered once, twice, three, or four times daily using any of the suitable methods described above. Furthermore, administration of the compound or treatment with the compound may continue for several days; for example, for a treatment cycle, treatment typically lasts at least 7, 14, or 28 days. Treatment cycles are often alternated between cycles with rest periods of approximately 1 to 28 days, typically approximately 7 days or approximately 14 days. In other embodiments, treatment cycles may also be continuous. In some embodiments, the methods provided herein comprise administering to a subject an initial daily dose of the compound described herein of about 1 to 800 mg, and increasing the dose incrementally until a clinical effect is achieved. The dose may be increased in increments of about 5, 10, 25, 50, or 100 mg. The dose may be increased daily, every other day, twice a week, or once a week. combination In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are combined with one or more additional therapeutic agents to treat or prevent the diseases or conditions disclosed herein. In some embodiments, the one or more additional therapeutic agents are one, two, three, or four additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents are one additional therapeutic agent. In some embodiments, the one or more additional therapeutic agents are two additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents are three additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents are four additional therapeutic agents. In some embodiments, the pharmaceutical composition provided herein comprises a compound of formula (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or a pharmaceutically acceptable salt thereof, and one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents are one, two, three, or four additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents are one additional therapeutic agent. In some embodiments, the one or more additional therapeutic agents are two additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents are three additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents are four additional therapeutic agents. In some embodiments, one or more additional therapeutic agents include, for example, inhibitory immune checkpoint blockers or inhibitors, stimulating immune checkpoint stimulants, agonists or activators, chemotherapeutic agents, anticancer agents, radiotherapy agents, anti-tumor agents, antiproliferative agents, anti-angiogenic agents, anti-inflammatory agents, immunotherapeutic agents, therapeutic antigen-binding molecules (e.g., mono- and multi-specific antibodies in any form, or fragments thereof, such as DART®, Duobody®, BiTE®, BiKE, TriKE, XmAb®, TandAb®, scFv, Fab, Fab derivatives), bispecific antibodies, non-immunoglobulin antibody mimics (e.g., including adnectin, affibody, affilin, affimer, affitin, alphabody, anti-carrier protein, peptide aptamer, armadillo repeat protein (ARM), atrimer, affinity multimer, and designed ankylosing repeat protein (DARPin). ® (fynomer, knottin, Kunitz domain peptide, monobody, and nanoCLAMP), antibody-drug conjugate (ADC), antibody-peptide conjugate), oncolytic virus, gene modifier or editor, cells containing chimeric antigen receptor (CAR) (e.g., including T cell immunotherapies, NK cell immunotherapies, or macrophage immunotherapies), cells containing engineered T cell receptor (TCR-T), or any combination thereof. Descriptive Objectives In some embodiments, one or more additional therapeutic agents include, for example, inhibitors, agonists, ligands, modulators, stimulants, blockers, activators, or inhibitors of a target (e.g., a peptide or polynucleotide), such as: 2'-5'-oligoadenylate synthase (OAS1; NCBI gene ID: 4938); 5'-3' exonuclease 1 (XRN1; NCBI gene ID: 54464); extracellular 5'-nucleotidase (NT5E, CD73; NCBI gene ID: 4907); ABL Proto-oncogene 1; non-receptor tyrosine kinases (ABL1, BCR-ABL, c-ABL, v-ABL; NCBI gene ID: 25); absent in melanoma 2 (AIM2; NCBI gene ID: 9447); acetyl-CoA acetylated transferase 2 (ACAA2; NCBI gene ID: 10499); acid phosphatase 3 (ACP3; NCBI gene ID: 55); adenosine deaminases (ADA, ADA1; NCBI gene ID: 100); adenosine receptors (e.g., ADORA1). (A1), ADORA2A (A2a, A2AR), ADORA2B (A2b, A2BR), ADORA3 (A3); NCBI gene IDs: 134, 135, 136, 137); AKT serine / threonine kinase 1 (AKT1, AKT, PKB; NCBI gene ID: 207); alanine aminopeptidase (membrane) (ANPEP, CD13; NCBI gene ID: 290); ALK receptor tyrosine kinase (ALK, CD242; NCBI gene ID: 238); alpha fetal protein (AFP; NCBI gene ID: 174); copper-containing amine oxidases (e.g., AOC1 (DAO1), AOC2, AOC3). (VAP1); NCBI gene ID: 26, 314, 8639); androgen receptor (AR; NCBI gene ID: 367); angiopoietin (ANGPT1, ANGPT2; NCBI gene ID: 284, 285); angiotensin II receptor type 1 (AGTR1; NCBI gene ID: 185); pro-angiotensin (AGT; NCBI gene ID: 183); apolipoprotein A1 (APOA1; NCBI gene ID: 335); apoptosis-inducing factor Mitochondrial-associated 1 (AIFM1, AIF; NCBI gene ID: 9131); arachidonic acid 5-lipoxygenase (ALOX5; NCBI gene ID: 240); aspartate aminotransferase (ASPG; NCBI gene ID: 374569); astrocyte homolog 1 (ASTE1; NCBI gene ID: 28990); ATM serine / threonine kinase (ATM; NCBI gene ID: 472); ATP-binding cassava family B member 1 (ABCB1, CD243, GP170);NCBI gene ID: 5243); ATP-dependent Clp protease (CLPP; NCBI gene ID: 8192); ATR serine / threonine kinase (ATR; NCBI gene ID: 545); AXL receptor tyrosine kinase (AXL; NCBI gene ID: 558); B and T lymphocyte-associated proteins (BTLA, CD272; NCBI gene ID: 151888); Baculovirus-containing IAP repeat proteins (BIRC2 (cIAP1), BIRC3 (cIAP2), XIAP (BIRC4, ...). IAP3), BIRC5 (survivin); NCBI gene ID: 329, 330, 331, 332); basigin (OK blood type) (BSG, CD147; NCBI gene ID: 682); B-cell lymphoma 2 (BCL2; NCBI gene ID: 596); BCL2 binding component 3 (BBC3, PUMA; NCBI gene ID: 27113); BCL2-like (e.g., BCL2L1 (Bcl-x), BCL2L2) (BIM); Bcl-x; NCBI gene ID: 598, 10018); β3-adrenergic receptor (ADRB3; NCBI gene ID: 155); bone γ-carboxyglutamic acid protein (BGLAP; NCBI gene ID: 632); bone morphogenetic protein 10 ligand (BMP10; NCBI gene ID: 27302); bradykinin receptors (e.g., BDKRB1, BDKRB2; NCBI gene ID: 623, 624); B-RAF (BRAF; NCBI gene ID: 273); breakpoint cluster region (BCR; NCBI gene ID: 613); Bromoare And the outer domain (BET) containing bromo domain proteins (e.g., BRD2, BRD3, BRD4, BRDT; NCBI gene ID: 6046, 8019, 23476, 676); Bruton's tyrosine kinase (BTK; NCBI gene ID: 695); cadherins (e.g., CDH3 (p-cadherin), CDH6 (k-cadherin); NCBI gene ID: 1001, 1004); cancer / testicular antigens (e.g., CTAG1A, CTAG1B, CTAG2; NCBI gene ID: 1485, 30848, 246100); cannabinoid receptors (e.g., CNR1). (CB1), CNR2 (CB2); NCBI gene ID: 1268, 1269); carbohydrate sulfonyltransferase 15 (CHST15; NCBI gene ID: 51363); carbonic anhydrases (e.g., CA1, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA8, CA9, CA10, CA11, CA12, CA13, CA14);NCBI gene IDs: 759, 760, 761, 762, 763, 765, 766, 767, 768, 770, 771, 11238, 23632, 56934, 377677; carcinoembryonic antigen-associated cell adhesion molecules (e.g., CEACAM3 (CD66d), CEACAM5 (CD66e), CEACAM6 (CD66c); NCBI gene IDs: 1048, 1084, 4680; casein kinases (e.g., CSNK1A1 (CK1), CSNK2A1). (CK2); NCBI gene ID: 1452, 1457); apoptotic proteases (e.g., CASP3, CASP7, CASP8; NCBI gene ID: 836, 840, 841, 864); catechol-β1 (CTNNB1; NCBI gene ID: 1499); cathepsin G (CTSG; NCBI gene ID: 1511); Cbl proto-oncogene B (CBLB, Cbl-b; NCBI gene ID: 868); CC motif chemokine ligand 21 (CCL21; NCBI gene ID: 6366); CC motif chemokine receptor 2 (CCR2; NCBI gene ID: 729230); CC motif chemokine receptors (e.g., CCR3 (CD193), CCR4 (CD194), CCR5 (CD195), CCR8). (CDw198); NCBI gene ID: 1232, 1233, 1234, 1237); CCAAT enhancer-binding protein α (CEBPA, CEBP; NCBI gene ID: 1050); Cell adhesion molecule 1 (CADM1; NCBI gene ID: 23705); Cell cycle 7 (CDC7; NCBI gene ID: 8317); Cell communication network factor 2 (CCN2; NCBI gene ID: 1490); Selenbrom (CRBN; NCBI gene ID: 51185); Checkpoint kinases (e.g., CHEK1 (CHK1), CHEK2) (CHK2); NCBI gene ID: 1111, 11200); Cholecystokinin B receptor (CCKBR; NCBI gene ID: 887); Human chorionic gonadotropin-prolactin 1 (CSH1; NCBI gene ID: 1442); Dendritic proteins (e.g., CLDN6, CLDN18; NCBI gene ID: 9074, 51208);Cluster of differentiation markers (such as CD1A, CD1C, CD1D, CD1E, CD2, CD3α (TRA), CDβ (TRB), CDγ (TRG), CDδ (TRD), CD4, CD8A, CD8B, CD19, CD20 (MS4A1), CD22, CD24, CD25 (IL2RA, TCGFR), CD28, CD33 (SIGLEC3), CD37, CD38, CD39 (ENTPD1), CD40 (TNFRSF5), CD44 (MIC4, PGP1), CD47 (IAP), CD48 (BLAST1), CD52, CD55 (DAF), CD58 (LFA3), CD74, CD79a, CD79b, CD80 (B7-1), CD84, CD86 (B7-2), CD96 (TACTILE), CD99 (MIC2), CD115 (CSF1R), CD116 (GMCSFR, CSF2RA), CD122 (IL2RB), CD123 (IL3RA), CD128 (IL8R1), CD132 (IL2RG), CD135 (FLT3), CD137 (TNFRSF9, 4-1BB), CD142 (TF, TFA), CD152 (CTLA4), CD160, CD182 (IL8R2), CD193 (CCR3), CD194 (CCR4), CD195 (CCR5), CD207, CD221 (IGF1R), CD222 (IGF2R), CD223 (LAG3), CD226 (DNAM1), CD244, CD247, CD248, CD276 (B7-H3), CD331 (FGFR1), CD332 (FGFR2), CD333 (FGFR3), CD334 (FGFR4);NCBI Gene IDs: 909, 911, 912, 913, 914, 919, 920, 923, 925, 926, 930, 931, 933, 940, 941, 942, 945, 951, 952, 953, 958, 960, 961, 962, 965, 972, 973, 974, 1043 1232, 1233, 1234, 1237, 1436, 1438, 1493, 1604, 2152, 2260, 2261, 2263, 2322, 3480, 3482, 3559, 3560, 3561, 3563, 3577, 3579, 3604, 3902, 4267, 6955 6957, 6964, 6965, 8832, 10666, 11126, 50489, 51744, 80381, 100133941; cluster proteins (CLU; NCBI gene ID: 1191); coagulation factors (e.g., F7, FXA; NCBI gene ID: 2155, 2159); collagen type IV α-chain (e.g., COL4A1, COL4A2, COL4A3, COL4A4, COL4A5; NCBI gene ID: 1282, 1284, 1285, 1286, 1287); collagen subfamily member 10 (COLEC10; NCBI gene ID: 10584); community stimulating factors (e.g., CSF1). (MCSF), CSF2 (GMCSF), CSF3 (GCSF); NCBI gene IDs: 1435, 1437, 1440); complement factors (e.g., C3, C5; NCBI gene IDs: 718, 727); COP9 signaling subunit 5 (COPS5; NCBI gene ID: 10987); C-type lectin domain family members (e.g., CLEC4C (CD303), CLEC9A (CD370), CLEC12A (CD371); CD371; NCBI gene IDs: 160364, 170482, 283420); CXC motif chemotherapeutic ligand 12 (CXCL12; NCBI gene ID: 6387); CXC motif chemotherapeutic receptors (CXCR1 (IL8R1, CD128), CXCR2 (IL8R2, CD182), CXCR3 (CD182, CD183, IP-10R), CXCR4 (CD184); NCBI gene IDs: 2833, 3577, 3579, 7852); periodic protein D1 (CCND1, BCL1; NCBI gene ID: 595); periodic protein-dependent kinases (e.g., CDK1, CDK2, CDK3, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK12);NCBI gene IDs: 983, 1017, 1018, 1019, 1020, 1021, 1022, 1024, 1025, 8558, 51755; cyclin G1 (CCNG1; NCBI gene ID: 900); cytochrome P450 family members (e.g., CYP2D6, CYP3A4, CYP11A1, CYP11B2, CYP17A1, CYP19A1, CYP51A1; NCBI gene IDs: 1565, 1576, 1583, 1585, 1586, 1588, 1595); cytochrome P450. P450 oxidoreductase (POR; NCBI gene ID: 5447); intercytokine-inducible SH2 protein (CISH; NCBI gene ID: 1154); cytotoxic T lymphocyte-associated protein 4 (CTLA4, CD152; NCBI gene ID: 1493); death box helicases (e.g., DDX5, DDX6, DDX58; NCBI gene ID: 1655, 1656, 23586); delta-like typical Notch ligands (e.g., DLL3, DLL4; NCBI gene ID: 10683, 54567); diablo IAP-binding mitochondrial proteins (DIABLO, SMAC; NCBI gene ID: 56616); diacylglycerol kinases (e.g., DGKA, DGKZ; NCBI gene ID: 1606, 8525); dickkopf WNT signaling pathway inhibitors (e.g., DKK1, DKK3; NCBI gene ID: 22943, 27122); dihydrofolate reductase (DHFR; NCBI gene ID: 1719); dihydropyrimidine dehydrogenase (DPYD; NCBI gene ID: 1806); dipeptidyl peptidase 4 (DPP4; NCBI gene ID: 1803); disk-based protein domain receptor tyrosine kinases (e.g., DDR1 (CD167), DDR2; CD167; NCBI gene IDs: 780, 4921); DNA-dependent protein kinases (PRKDC; NCBI gene ID: 5591); DNA topoisomerases (TOP1, TOP2A, TOP2B, TOP3A, TOP3B; NCBI gene IDs: 7150, 7153, 7155, 7156, 8940); Dopachrome tautomerase (DCT; NCBI gene ID: 1638); Dopamine receptor D2 (DRD2; NCBI gene ID: 1318); DOT1-like histone lysine methyltransferase (DOT1L; NCBI gene ID: 84444); Exonucleotide pyrophosphatase / phosphodiesterase 3 (ENPP3, CD203c; NCBI gene ID: 5169); EMAP-like 4 (EML4; NCBI gene ID: 27436); Endothelial glycoprotein (ENG; NCBI gene ID: 2022);Endoplasmic reticulum aminopeptidases (e.g., ERAP1, ERAP2; NCBI gene ID: 51752, 64167); enhancers of the second unit of the Zeste 2 polycomb inhibitory complex (EZH2; NCBI gene ID: 2146); pterin receptors (e.g., EPHA1, EPHA2, EPHA3, EPHA4, EPHA5, EPHA7, EPHB4; NCBI gene ID: 1969, 2041, 2042, 2043, 2044, 2045, 2050); pterin (e.g., EFNA1, EFNA4, EFNB2; NCBI gene ID: 1942, 1945, 1948); epidermal growth factor receptors (e.g., ERBB1 (HER1, EGFR), ERBB1 variant III (EGFRvIII), ERBB2 (HER2, NEU, CD340), ERBB3 (HER3), ERBB4). (HER4); NCBI gene ID: 1956, 2064, 2065, 2066); Epithelial cell adhesion molecule (EPCAM; NCBI gene ID: 4072); Epithelial cleavage-inducing substance (EPGN; NCBI gene ID: 255324); Eukaryotic translation elongation factors (e.g., EEF1A2, EEF2; NCBI gene ID: 1917, 1938); Eukaryotic translation initiation factors (e.g., EIF4A1, EIF5A; NCBI gene ID: 1973, 1984); Efferentiation protein 1 (XP) O1; NCBI gene ID: 7514); farnesoid X receptors (NR1H4, FXR; NCBI gene ID: 9971); Fas ligands (FASLG, FASL, CD95L, CD178, TNFSF6; NCBI gene ID: 356); fatty acid amide hydrolase (FAAH; NCBI gene ID: 2166); fatty acid synthase (FASN; FAS; NCBI gene ID: 2194); Fc fragments of Ig receptors (e.g., FCER1A, FCGRT, FCGR3A) (CD16); NCBI gene ID: 2205, 2214, 2217); Fc receptor-like 5 (FCRL5, CD307; NCBI gene ID: 83416); Fibroblast activation protein α (FAP; NCBI gene ID: 2191); Fibroblast growth factor receptors (e.g., FGFR1 (CD331), FGFR2 (CD332), FGFR3 (CD333), FGFR4 (CD334); NCBI gene ID: 2260, 2261, 2263, 2264); Fibroblast growth factors (e.g., FGF1 (FGF α), FGF2 (FGF β), FGF4, FGF5; NCBI gene ID: 2246, 2247, 2249, 2250); Fibronectin 1 (FN1, MSF);NCBI Gene ID: 2335); fms-related receptor tyrosine kinases (e.g., FLT1 (VEGFR1), FLT3 (STK1, CD135), FLT4) (VEGFR2); NCBI gene ID: 2321, 2322, 2324); FMS-related receptor tyrosine kinase 3 ligand (FLT3LG; NCBI gene ID: 2323); Local adhesion kinase 2 (PTK2, FAK1; NCBI gene ID: 5747); Folate hydrolase 1 (FOLH1, PSMA; NCBI gene ID: 2346); Folate receptor 1 (FOLR1; NCBI gene ID: 2348); Forkhead box protein M1 (FOXM1; NCBI gene ID: 2305); Furrin protease (FURIN, PACE; NCBI gene ID: 5045); FYN tyrosine kinase (FYN, SYN; NCBI gene ID: 2534); Galactolectins (e.g., LGALS3, LGALS8) (PCTA1), LGALS9; NCBI gene ID: 3958, 3964, 3965); Glucocorticoid receptor (NR3C1, GR; NCBI gene ID: 2908); Glucuronidase β (GUSB; NCBI gene ID: 2990); Glutamate metabolite receptor 1 (GRM1; NCBI gene ID: 2911); Glutamate oxidase (GLS; NCBI gene ID: 2744); Glutathione S-transferase π (GSTP1; NCBI gene ID: 2950); Glycosyl synthase kinase 3β (GSK3B; NCBI gene ID: 2932); Phosphatidylinositol polysaccharide 3 (GPC3; NCBI gene ID: 2719); Gonadotropin-releasing hormone 1 (GNRH1; NCBI gene ID: 2796) ); Gonadotropin-releasing hormone receptor (GNRHR; NCBI gene ID: 2798); GPNMB glycoprotein nmb (GPNMB, osteocalcin; NCBI gene ID: 10457); Growth differentiation factor 2 (GDF2, BMP9; NCBI gene ID: 2658); Growth factor receptor binding protein 2 (GRB2, ASH; NCBI gene ID: 2885); Guanylate cyclase 2C (GUCY2C, STAR, MECIL, MUCIL; NCBI gene ID: 2984); H19 maternal imprinted transcripts (H19; NCBI gene ID: 283120); HCK proto-oncogene, Src family tyrosine kinase (HCK; NCBI gene ID: 3055); Heat shock proteins (e.g., HSPA5) (HSP70, BIP, GRP78), HSPB1 (HSP27), HSP90B1 (GP96); NCBI Gene IDs: 3309, 3315, 7184).Blood matrix oxygenases (e.g., HMOX1 (HO1), HMOX2 (HO1); NCBI gene ID: 3162, 3163); heparinase (HPSE; NCBI gene ID: 10855); hepatitis A virus cellular receptor 2 (HAVCR2, TIM3, CD366; NCBI gene ID: 84868); hepatocyte growth factor (HGF; NCBI gene ID: 3082); HERV-H LTR-associated 2 (HHLA2, B7-H7; NCBI gene ID: 11148); histamine receptor H2 (HRH2; NCBI gene ID: 3274); histone deacetylases (e.g., HDAC1, HDAC7, HDAC9; NCBI gene ID: 3065, 9734, 51564); HRAs proto-oncogenes (GTPases) (HRAS; NCBI gene ID: 3265); hypoxia-inducible factors (e.g., HIF1A, HIF2A (EPAS1); NCBI gene ID: 2034, 3091); I-κ-B kinase (IKK β; NCBI gene ID: 3551, 3553); IKAROS family zinc fingers (IKZF1) (LYF1), IKZF3; NCBI gene ID: 10320, 22806); Immunoglobulin superfamily member 11 (IGSF11; NCBI gene ID: 152404); Indoleamine 2,3-dioxygenase (e.g., IDO1, IDO2; NCBI gene ID: 3620, 169355); Inducible T cell costimulators (ICOS, CD278; NCBI gene ID: 29851); Inducible T cell costimulator ligands (ICOSLG, B7-H2; NCBI gene ID: 23308); Insulin-like growth factor receptors (e.g., IGF1R, IGF2R; NCBI gene ID: 3480, 3482); Insulin-like growth factors (e.g., IGF1, IGF2; NCBI gene ID: 3479, 3481); Insulin receptors (INSR, CD220; NCBI gene ID: 3643); Integrin subunits (e.g., ITGA5) (CD49e), ITGAV (CD51), ITGB1 (CD29), ITGB2 (CD18, LFA1, MAC1), ITGB7; NCBI gene IDs: 3678, 3685, 3688, 3695, 3698); intercellular adhesion molecule 1 (ICAM1, CD54; NCBI gene ID: 3383); interleukin-1 receptor-associated kinase 4 (IRAK4; NCBI gene ID: 51135);Interleukin receptors (e.g., IL2RA (TCGFR, CD25), IL2RB (CD122), IL2RG (CD132), IL3RA, IL6R, IL13RA2 (CD213A2), IL22RA1; NCBI gene IDs: 3598, 3559, 3560, 3561, 3563, 3570, 58985); interleukins (e.g., IL1A, IL1B, IL2, IL3, IL6 (HGF), IL7, IL8 (CXCL8), IL10 (TGIF), IL12A, IL12B, IL15, IL17A (CTLA8), IL18, IL23A, IL24, IL-29) (IFNL1); NCBI gene IDs: 3552, 3553, 3558, 3562, 3565, 3569, 3574, 3586, 3592, 3593, 3600, 3605, 3606, 11009, 51561, 282618; isocitrate dehydrogenase (NADP(+)1) (e.g., IDH1, IDH2; NCBI gene IDs: 3417, 3418); Janus kinase (e.g., JAK1, JAK2, JAK3; NCBI gene IDs: 3716, 3717, 3718); bradykinin-related peptidase 3 (KLK3; NCBI gene ID: 354); killer cell immunoglobulin-like receptor, Ig domain, and long cytoplasmic tail (e.g., KIR2DL1 (CD158A), KIR2DL2 (CD158B1), KIR2DL3). (CD158B), KIR2DL4 (CD158D), KIR2DL5A (CD158F), KIR2DL5B, KIR3DL1 (CD158E1), KIR3DL2 (CD158K), KIR3DP1 (CD158c), KIR2DS2 (CD158J); NCBI gene IDs: 3802, 3803, 3804, 3805, 3811, 3812, 57292, 553128, 548594, 100132285; killer cell lectin-like receptors (e.g., KLRC1 (CD159A), KLRC2 (CD159c), KLRC3, KLRRC4, KLRD1 (CD94), KLRG1, KLRK1 (NKG2D, CD314); NCBI gene IDs: 3821, 3822, 3823, 3824, 8302, 10219, 22914; kinase insertion domain receptors (KDR, CD309, VEGFR2; NCBI gene ID: 3791); kinin family member 11 (KIF11; NCBI gene ID: 3832); KiSS-1 transfer inhibitor (KISS1; NCBI gene ID: 3814);KIT proto-oncogene, receptor tyrosine kinase (KIT, C-KIT, CD117; NCBI gene ID: 3815); KRAS proto-oncogene (GTPase) (KRAS; NCBI gene ID: 3845); lactoferrin (LTF; NCBI gene ID: 4057); LCK proto-oncogene, Src family tyrosine kinase (LCK; NCBI gene ID: 3932); LDL receptor-associated protein 1 (LRP1, CD91, IGFBP3R; NCBI gene ID: 4035); leucine-rich repeat 15 (LRRC15; NCBI gene ID: 131578); leukocyte immunoglobulin-like receptors (e.g., LILRB1 (ILT2, CD85J), LILRB2 (ILT4, ...). CD85D; NCBI gene ID: 10288, 10859); Leukotriene A4 hydrolase (LTA4H; NCBI gene ID: 4048); Activated T cell linker (LAT; NCBI gene ID: 27040); Luteinizing growth hormone / human chorionic gonadotropin receptor (LHCGR; NCBI gene ID: 3973); LY6 / PLAUR domain-containing 3 (LYPD3; NCBI gene ID: 27076); Lymphocyte activation 3 (LAG3; CD223; NCBI gene ID: 3902); Lymphocyte antigens (e.g., LY9 (CD229), LY75) (CD205); NCBI gene ID: 4063, 17076); LYN proto-oncogene, Src family tyrosine kinase (LYN; NCBI gene ID: 4067); Lymphocyte cytoplasmic protein 2 (LCP2; NCBI gene ID: 3937); Lysine demethylase 1A (KDM1A; NCBI gene ID: 23028); Lysophosphatidyl receptor 1 (LPAR1, EDG2, LPA1, GPR26; NCBI gene ID: 1902); Lysine oxygenase (LOX; NCBI gene ID: 4015); Lysine oxygenase-like 2 (LOXL2; NCBI gene ID: 4017); Macrophage migration inhibitory factor (MIF, GIF; NCBI gene ID: 4282); Macrophage stimulation 1 receptor (MST1R, CD136; NCBI gene ID: 4486); MAGE family members (e.g., MAGEA1, MAGEA2, MAGEA2B, MAGEA3, MAGEA4, MAGEA5, MAGEA6, MAGEA10, MAGEA11, MAGEC1, MAGEC2, MAGED1, MAGED2; NCBI gene IDs: 4100, 4101, 4102, 4103, 4104, 4105, 4109, 4110, 9500, 9947, 10916, 51438, 266740);Major histocompatibility complexes (e.g., HLA-A, HLA-E, HLA-F, HLA-G; NCBI gene IDs: 3105, 3133, 3134, 3135); fornix main proteins (MVP, VAULT1; NCBI gene ID: 9961); MALT1 para-apoptotic protease (MALT1; NCBI gene ID: 10892); MAPK activated protein kinase 2 (MAPKAPK2; NCBI gene ID: 9261); MAPK interacting serine / threonine kinases (e.g., MKNK1, MKNK2; NCBI gene IDs: 2872, 8569); matrix metallopeptidases (e.g., MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13, MMP...). 14. MMP15, MMP16, MMP17, MMP19, MMP20, MMP21, MMP24, MMP25, MMP26, MMP27, MMP28; NCB I gene ID: 4312, 4313, 4314, 4316, 4317, 4318, 4319, 4320, 4321, 4322, 4323, 4324, 4325, 43 26, 4327, 9313, 10893, 56547, 64066, 64386, 79148, 118856); MCL1 apoptosis regulator, BCL2 family member (MCL1; NCBI gene ID: 4170); MDM2 proto-oncogene (MDM2; NCBI gene ID: 4193); p53 MDM4 regulator (MDM4; BMFS6; NCBI gene ID: 4194); Mechanotargets of rapamycin kinase (MTOR, FRAP1; NCBI gene ID: 2475); melan-A (MLANA; NCBI gene ID: 2315); melanocortin receptors (MC1R, MC2R; NCBI gene ID: 4157, 4148); MER proto-oncogene, tyrosine kinase (MERTK; NCBI gene ID: 10461); mesothelin (MSLN; NCBI gene ID: 10232); MET proto-oncogene, receptor tyrosine kinase (MET, c-Met, HGFR; NCBI gene ID: 4233); methionine aminopeptidase 2 (METAP2, MAP2; NCBI gene ID: 10988); MHC type I polypeptide-related sequences (e.g., MICA, MICB; NCBI gene ID: 4277, 100507436); cleavage-activated protein kinases (e.g., MAPK1) (ERK2), MAPK3 (ERK1), MAPK8 (JNK1), MAPK9 (JNK2), MAPK10 (JNK3), MAPK11 (p38 β), MAPK12;NCBI gene IDs: 5594, 5595, 5599, 5600, 5601, 5602, 819251; cleavage-activated protein kinase kinases (e.g., MAP3K5 (ASK1), MAP3K8 (TPL2, AURA2); NCBI gene IDs: 4217, 1326); cleavage-activated protein kinase kinase 1s (MAP4K1, HPK1; NCBI gene ID: 11184); cleavage-activated protein kinase kinases (e.g., MAP2K1 (MEK1), MAP2K2 (MEK2), MAP2K7). (MEK7); NCBI gene ID: 5604, 5605, 5609); MPL proto-oncogene, thrombopoietin receptor (MPL; NCBI gene ID: 4352); mucins (e.g., MUC1 (including its splice variants (e.g., including MUC1 / A, C, D, X, Y, Z, and REP)), MUC5AC, MUC16) (CA125); NCBI gene IDs: 4582, 4586, 94025); MYC proto-oncogene, bHLH transcription factor (MYC; NCBI gene ID: 4609); myostatin (MSTN, GDF8; NCBI gene ID: 2660); myristylated alanine protein kinase C receptor (MARCKS; NCBI gene ID: 4082); natriuretic peptide receptor 3 (NPR3; NCBI gene ID: 4883); natural killer cell cytotoxic receptor 3 ligand 1 (NCR3LG1, B7-H6; NCBI gene ID: 374383); neuronal growth inhibitory factor, MAGE family member (NDN; NCBI gene ID: 4692); connective cell adhesion molecules (e.g., NECTIN2 (CD112, PVRL2), NECTIN4). (PVRL4); NCBI gene ID: 5819, 81607); Neural cell adhesion molecule 1 (NCAM1, CD56; NCBI gene ID: 4684); Neurocilia proteins (e.g., NRP1 (CD304, VEGF165R), NRP2 (VEGF165R2); NCBI gene ID: 8828, 8829); Neurotrophic receptor tyrosine kinases (e.g., NTRK1 (TRKA), NTRK2 (TRKB), NTRK3) (TRKC); NCBI gene ID: 4914, 4915, 4916); NFKB activator (NKAP; NCBI gene ID: 79576); NIMA-associated kinase 9 (NEK9; NCBI gene ID: 91754); NLR family pyoside domain 3 (NLRP3, NALP3; NCBI gene ID: 114548); Notch receptors (e.g., NOTCH1, NOTCH2, NOTCH3, NOTCH4);NCBI gene IDs: 4851, 4853, 4854, 4855); NRAS proto-oncogene (GTPase) (NRAS; NCBI gene ID: 4893); nuclear factor κB (NFKB1, NFKB2; NCBI gene IDs: 4790, 4791); nuclear factor, erythroblast-like 2 (NFE2L2; NRF2; NCBI gene ID: 4780); nuclear receptor subfamily 4A member 1 (NR4A1; NCBI gene ID: 3164); nucleolin (NCL; NCBI gene ID: 4691); nucleolar phosphoprotein 1 (NPM1; NCBI gene ID: 4869); nucleotide-binding oligomer domain 2 (NOD2; NCBI gene ID: 64127); nudix hydrolase 1 (NUDT1; NCBI gene ID: 4521); O-6-methylguanine-DNA methyltransferase (MGMT; NCBI gene ID: 4255); ...3); nuclear Opium receptor δ1 (OPRD1; NCBI gene ID: 4985); ornithine decarboxylase 1 (ODC1; NCBI gene ID: 4953); levoglutarate dehydrogenase (OGDH; NCBI gene ID: 4967); parathyroxine (PTH; NCBI gene ID: 5741); PD-L1 (CD274; NCBI gene ID: 29126); periostrin (POSTN; NCBI gene ID: 10631); peroxisome proliferation-activating receptor (e.g., PPARα) (PPARα), PPARD (PPARδ), PPARG (PPARγ); NCBI gene IDs: 5465, 5467, 5468); phosphatases and tensin homologs (PTEN; NCBI gene ID: 5728); phosphatidylinositol-4,5-bisphosphonate 3-kinases (PIK3CA (PI3Kα), PIK3CB (PI3Kβ), PIK3CD (PI3Kδ), PIK3CG (PI3Kα) γ); NCBI gene IDs: 5290, 5291, 5293, 5294; phospholipases (e.g., PLA2G1B, PLA2G2A, PLA2G2D, PLA2G3, PLA2G4A, PLA2G5, PLA2G7, PLA2G10, PLA2G12A, PLA2G12B, PLA2G15; NCBI gene IDs: 5319, 5320, 5321, 5322, 7941, 8399, 50487, 23659, 26279, 81579, 84647); Pim proto-oncogenes, serine / threonine kinases (e.g., PIM1, PIM2, PIM3; NCBI gene IDs: 5292, 11040, 415116); placental growth factor (PGF; NCBI gene ID: 5228);Plasminogen activator, urokinase (PLAU, u-PA, ATF; NCBI gene ID: 5328); platelet-derived growth factor receptors (e.g., PDGFRA (CD140A, PDGFR2), FDGFRB (CD140B, ...). PDGFR1; NCBI gene ID: 5156, 5159); plexin B1 (PLXNB1; NCBI gene ID: 5364); poliovirus receptor (PVR) cell adhesion molecules (PVR, CD155; NCBI gene ID: 5817); polo-like kinase 1 (PLK1; NCBI gene ID: 5347); poly(ADP-ribose) polymerases (e.g., PARP1, PARP2, PARP3; NCBI gene ID: 142, 10038, 10039); polycomb protein EED (EED; NCBI gene ID: 8726); porcupine O-acetylglucosyltransferase (PORCN; NCBI gene ID: 64840); PRAME nuclear receptor transcription regulator (PRAME; NCBI gene ID: 23532); promelanosome protein (PM EL; NCBI gene ID: 6490); Progesterone receptor (PGR; NCBI gene ID: 5241); Programmed cell death 1 (PDCD1, PD-1, CD279; NCBI gene ID: 5133); Programmed cell death 1 ligand 2 (PDCD1LG2, CD273, PD-L2; NCBI gene ID: 80380); Convexin 1 (PROM1, CD133; NCBI gene ID: 8842); Promyelocytic leukemia (PML; NCBI gene ID: 5371); Sphingolipid-activated protein (PSAP; NCBI gene ID: 5660); Prostaglandin E receptor 4 (PTGER4; NCBI gene ID: 5734); Prostaglandin E synthase (PTGES; NCBI gene ID: 9536); Prostaglandin-endoperoxidase (PTGS1) (COX1), PTGS2 (COX2); NCBI gene ID: 5742, 5743); proteasome 20S subunit β9 (PSMB9; NCBI gene ID: 5698); protein arginine methyltransferases (e.g., PRMT1, PRMT5; NCBI gene ID: 3276, 10419); protein kinase N3 (PKN3; NCBI gene ID: 29941); protein phosphatase 2A (PPP2CA; NCBI gene ID: 5515); protein tyrosine kinase 7 (inactive) (PTK7; NCBI gene ID: 5754); protein tyrosine phosphatase receptors (PTPRB (PTPB), PTPRC (CD45R); NCBI gene ID: 5787, 5788); prothymosin α (PTMA; NCBI gene ID: 5757);Purine nucleoside phosphorylase (PNP; NCBI gene ID: 4860); purine receptor P2X7 (P2RX7; NCBI gene ID: 5027); PVR-associated immunoglobulin domain (PVRIG, CD112R; NCBI gene ID: 79037); Raf-1 proto-oncogene, serine / threonine kinase (RAF1, c-Raf; NCBI gene ID: 5894); RAR-associated orphan receptor γ (RORC; NCBI gene ID: 6097); ras homolog family member C (RHOC); NCBI gene ID: 389); Ras homolog, mTORC1 binding (RHEB; NCBI gene ID: 6009); RB transcriptional co-repressor 1 (RB1; NCBI gene ID: 5925); receptor-interacting serine / threonine protein kinase 1 (RIPK1; NCBI gene ID: 8737); ret pro-oncogene (RET; NCBI gene ID: 5979); early retinoic acid transcripts (e.g., RAET1E, RAET1G, RAET1L; NCBI Gene IDs: 135250, 154064, 353091; retinoic acid receptor α (e.g., RARA, RARG; NCBI gene IDs: 5914, 5916); visual pigment X receptor (e.g., RXRA, RXRB, RXRG; NCBI gene IDs: 6256, 6257, 6258); Rho-related coiled-coil protein kinases (e.g., ROCK1, ROCK2; NCBI gene IDs: 6093, 9475); ribosomal protein S6 kinase B1 (RPS6KB1, S6K-β) 1; NCBI gene ID: 6198); Ring finger protein 128 (RNF128, GRAIL; NCBI gene ID: 79589); ROS proto-oncogene 1, receptor tyrosine kinase (ROS1; NCBI gene ID: 6098); Circular guide receptor 4 (ROBO4; NCBI gene ID: 54538); RUNX family transcription factor 3 (RUNX3; NCBI gene ID: 864); S100 calcium-binding protein A9 (S100A9; NCBI gene ID: 6280); Secretion coil-associated protein 2 (SFRP2; NCBI gene ID: 6423); Secretion phosphoprotein 1 (SPP1; NCBI gene ID: 6696); Secretion globulin family 1A member 1 (SCGB1A1; NCBI gene ID: 7356); Selectins (e.g., SELE, SELL (CD62L), SELP) (CD62); NCBI gene ID: 6401, 6402, 6403); semaphorin 4D (SEMA4D; CD100; NCBI gene ID: 10507);Sialic acid-binding Ig-like lectins (SIGLEC7 (CD328), SIGLEC9 (CD329), SIGLEC10; NCBI gene IDs: 27036, 27180, 89790); signal regulatory protein α (SIRPA, CD172A; NCBI gene ID: 140885); signal transducers and transcriptional activators (e.g., STAT1, STAT3, STAT5A, STAT5B; NCBI gene IDs: 6772, 6774, 6776, 6777); longevity protein 3 (SIRT3; NCBI gene ID: 23410); members of the SLAM family of signaling lymphocyte activators (e.g., SLAMF1 (CD150), SLAMF6 (CD352), SLAMF7 (CD319), SLAMF8). (CD353), SLAMF9; NCBI gene ID: 56833, 57823, 89886, 114836); SLIT and NTRK-like family member 6 (SLITRK6; NCBI gene ID: 84189); Smoothed coil type receptor (SMO; NCBI gene ID: 6608); Soluble epoxide hydrolase 2 (EPHX2; NCBI gene ID: 2053); Solute carrier family members (e.g., SLC3A2 (CD98), SLC5A5, SLC6A2, SLC10A3, SLC34A2, SLC39A6, SLC43A2) (LAT4), SLC44A4; NCBI gene IDs: 6520, 6528, 6530, 8273, 10568, 25800, 80736, 124935; somatostatin receptors (e.g., SSTR1, SSTR2, SSTR3, SSTR4, SSTR5; NCBI gene IDs: 6751, 6752, 6753, 6754, 6755); sonic hedgehog protein communication molecule (SHH; NCBI gene ID: 6469); Sp1 transcription factor (SP1; NCBI gene ID: 6667); neuroamine kinases (e.g., SPHK1, SPHK2; NCBI gene IDs: 8877, 568). 48); Neurolamine-1-phosphate receptor 1 (S1PR1, CD363; NCBI gene ID: 1901); Spleen-associated tyrosine kinase (SYK; NCBI gene ID: 6850); Splicing factor 3B factor 1 (SF3B1; NCBI gene ID: 23451); SRC proto-oncogene, non-receptor tyrosine kinase (SRC; NCBI gene ID: 6714); Stabilin 1 (STAB1, CLEVER-1; NCBI gene ID: 23166); STEAP family member 1 (STEAP1; NCBI gene ID: 26872); Steroid sulfatase (STS; NCBI gene ID: 412);Interferon-responsive cGAMP-interacting protein-stimulating factor 1 (STING1; NCBI gene ID: 340061); superoxide dismutase 1 (SOD1, ALS1; NCBI gene ID: 6647); intercytokine signaling inhibitors (SOCS1 (CISH1), SOCS3 (CISH3; NCBI gene ID: 8651, 9021); synaptic protein 3 (SYN3; NCBI gene ID: 8224); cohesin-glycan 1 (SDC1, CD138, cohesin-glycan; NCBI gene ID: 6382); conuclear protein α (SNCA, PARK1; NCBI gene ID: 6622); T-cell immunoglobulin and mucin domain-containing 4 (TIMD4, SMUCKLER; NCBI gene ID: 91937); T-cell immune receptor with Ig and ITIM domains (TIGIT; NCBI gene ID: 201633); tachykinin receptors (e.g., TACR1, TACR3; NCBI gene ID: 6869, 6870); TANK-binding kinase 1 (TBK1; NCBI gene ID: 29110); end-anchored polymerase (TNKS; NCBI gene ID: 8658); TATA box-binding protein-associated factors, RNA polymerase I subunit B (TAF1B; NCBI gene ID: 9014); T-box transcription factor T (TBXT; NCBI gene ID: 6862); TCDD-induced polymerase (A DP-ribose) polymerase (TIPARP, PAPR7; NCBI gene ID: 25976); tec protein tyrosine kinase (TEC; NCBI gene ID: 7006); TEK receptor tyrosine kinase (TEK, CD202B, TIE2; NCBI gene ID: 7010); telomerase reverse transcriptase (TERT; NCBI gene ID: 7015); tendinin C (TNC; NCBI gene ID: 3371); three major repair exonucleases (e.g., TREX1, TREX2; NCBI gene ID: 1). 1277, 11219); thrombin modulators (THBD, CD141; NCBI gene ID: 7056); thymidine kinases (e.g., TK1, TK2; NCBI gene ID: 7083, 7084); thymidine phosphorylase (TYMP; NCBI gene ID: 1890); thymidine nucleotide synthase (TYMS; NCBI gene ID: 7298); thyroxine receptors (THRA, THRB; NCBI gene ID: 7606, 7608); thyrotropin receptors (TSHR; NCBI gene ID: 7253);TNF superfamily members (e.g., TNFSF4 (OX40L, CD252), TNFSF5 (CD40L), TNFSF7 (CD70), TNFSF8 (CD153, CD30L), TNFSF9 (4-1BB-L, CD137L), TNFSF10 (TRAIL, CD253, APO2L), TNFSF11 (CD254, RANKL2, TRANCE), TNFSF13 (APRIL, CD256, TRAIL2), TNFSF13b (BAFF, BLYS, CD257), TNFSF14 (CD258, LIGHT), TNFSF18 (GITRL); NCBI gene IDs: 944, 959, 970, 7292, 8600, 8740, 8741, 8743, 8744, 8995); TLR receptors (e.g., TLR1 (CD281), TLR2 (CD282), TLR3). (CD283), TLR4 (CD284), TLR5, TLR6 (CD286), TLR7, TLR8 (CD288), TLR9 (CD289), TLR10 (CD290); NCBI gene IDs: 7096, 7097, 7098, 7099, 10333, 51284, 51311, 54106, 81793; transferrin (TF; NCBI gene ID: 7018); transferrin receptors (TFRC, CD71; NCBI gene ID: 7037); transforming growth factors (e.g., TGFA, TGFB1; NCBI gene IDs: 7039, 7040); transforming growth factor receptors (e.g., TGFBR1, TGFBR2, TGFBR... 3; NCBI gene IDs: 7046, 7048, 7049); Transgenic protein E7 (E7; NCBI gene ID: 1489079); Transglutaminase 5 (TGM5; NCBI gene ID: 9333); Transient receptor potential cation channel subfamily V member 1 (TRPV1, VR1; NCBI gene ID: 7442); Transmembrane and immunoglobulin domain-containing 2 (TMIGD2, CD28H, IGPR1; NCBI gene ID: 126259); Trigger receptors for bone marrow cell expression (e.g., TREM1). (CD354), TREM2; NCBI gene ID: 54209, 54210); nutritional proteins (TRO, MAGED3; NCBI gene ID: 7216); trophoblast glycoprotein (TPBG; NCBI gene ID: 7162); tryptophan 2,3-dioxygenase (TDO2; NCBI gene ID: 6999); tryptophan hydroxylase (e.g., TPH1, TPH2; NCBI gene ID: 7166, 121278);Tumor-associated calcium signaling transducers 2 (TACSTD2, TROP2, EGP1; NCBI gene ID: 4070); tumor necrosis factor (TNF; NCBI gene ID: 7124); members of the tumor necrosis factor (TNF) receptor superfamily (e.g., TNFRSF1A (CD120a), TNFRSF1B (CD120b), TNFRSF4 (OX40), TNFRSF5 (CD40), TNFRSF6 (CD95, FAS receptor), TNFRSF7 (CD27), TNFRSF8 (CD30), TNFRSF9 (CD137, 4-1BB), TNFRSF10A (CD261), TNFRSF10B (TRAIL, DR5, CD262), TNFRSF10C, TNFRSF10D, TNFRSF11A, TNFRSF11B (OPG), TNFRSF12A, TNFRSF13B, TNFR13C (CD268, BAFFR), TNFRSF14 (CD270, LIGHTR), TNFRSF16, TNFRSF17 (CD269, BCMA), TNFRSF18 (GITR, CD357), TNFRSF19, TNFRSF21, TNFRSF25; NCBI gene IDs: 355, 608, 939, 943, 958, 3604, 4804, 4982, 7132, 7133, 7293, 8718, 8764, 8784, 8792, 8793, 8794, 8795, 8797, 23495, 27242, 51330, 55504; tumor protein p53 (TP53; NCBI gene ID: 7157); tumor suppressor 2, mitochondrial calcium regulator (T USC2; NCBI gene ID: 11334); TYRO3 protein tyrosine kinase (TYRO3; BYK; NCBI gene ID: 7301); tyrosinase (TYR; NCBI gene ID: 7299); tyrosine hydroxylase (TH; NCBI gene ID: 7054); tyrosine kinase 1 with immunoglobulin-like and EGF-like domains (e.g., TIE1, TIE1; NCBI gene ID: 7075); tyrosine protein phosphatase non-receptor type 11 (PTPN11, SHP2; NCBI gene ID: 5781); ubiquitin conjugase E2 I (UBE2I, UBC9; NCBI gene ID: 7329); ubiquitin C-terminal hydrolase L5 (UCHL5; NCBI gene ID: 51377); ubiquitin-specific peptidase 7 (USP7; NCBI gene ID: 7874); ubiquitin-like modifier activator 1 (UBA1; NCBI gene ID: 7317); UL16 binding proteins (e.g., ULBP1, ULBP2, ULBP3);NCBI gene IDs: 79465, 80328, 80328); valine-containing proteins (VCP, CDC48; NCBI gene ID: 7415); vascular cell adhesion molecule 1 (VCAM1, CD106; NCBI gene ID: 7412); vascular endothelial growth factors (e.g., VEGFA, VEGFB; NCBI gene IDs: 7422, 7423); vimentin (VIM; NCBI gene ID: 7431); vitamin D receptor (VDR; NCBI gene ID: 7421); T cell activation inhibitor 1 containing V-set domain (TCN1, B7-H4; NCBI gene ID: 79679); V-set immunomodulatory receptors (VSIR, VISTA, B7-H5; NCBI gene ID: 64115); WEE1 G2 checkpoint kinase (WEE1; NCBI gene ID: 7465); WRN-like RecQ helicases (WRN; RECQ3; NCBI gene ID: 7486); WT1 transcription factor (WT1; NCBI gene ID: 7490); WW domain-containing transcriptional regulator 1 (WWTR1; TAZ; NCBI gene ID: 25937); XC motif chemokine ligand 1 (XCL1, ATAC; NCBI gene ID: 6375); XC motif chemokine receptor 1 (XCR1, GPR5, CCXCR1; NCBI gene ID: 2829); Yes1-related transcriptional regulator (YAP1; NCBI gene ID: 10413); or ζ chain-associated protein kinase 70 (ZAP70; NCBI gene ID: 7535). In some embodiments, one or more additional therapeutic agents include, for example, agents targeting the following: extracellular 5'-nucleotidases (NT5E or CD73; NCBI gene ID: 4907); adenosine A. 2A Receptor (ADORA2A; NCBI gene ID: 135); Adenosine A 2BReceptors (ADORA2B; NCBI gene ID: 136); CC motif chemokine receptor 8 (CCR8, CDw198; NCBI gene ID: 1237); cytokinin-inducible SH2 protein (CISH; NCBI gene ID: 1154); diacylglycerol kinase α (DGKA, DAGK, DAGK1, or DGK-α; NCBI gene ID: 1606); fms-like tyrosine kinase 3 (FLT3, CD135; NCBI gene ID: 2322); integrin-associated protein (IAP, CD47; NCBI gene ID: 961); interleukin 2 (IL2; NCBI gene ID: 3558); interleukin 2 receptor (IL2RA, IL2RB, IL2RG; NCBI gene ID: 3559, 3560, 3561); Kirsten rat sarcoma virus (KRAS; NCBI gene ID: 3845; including mutations such as KRAS) G12C or G12D); cleavage-inducing protein kinase kinase 1 (MAP4K1) (also known as hematopoietic progenitor cell kinase 1) (HPK1, NCBI gene ID: 11184); Myeloid Leukemia Sequence 1 Apoptosis Regulator (MCL1; NCBI gene ID: 4170); Phosphatidylinositol-4,5-bisphosphonate 3-kinase, Enzyme Catalytic Subunit δ (PIK3CD; NCBI gene ID: 5293); Programmed Death Ligand 1 (PD-L1, CD274; NCBI gene ID: 29126); Programmed Cell Death Protein 1 (PD-1, CD279; NCBI gene ID: 5133); Proto-oncogene c-KIT (KIT, CD117; NCBI gene ID: 3815); Signal Regulatory Protein α (SIRPA, CD172A; NCBI gene ID: 140885); TCDD-Inducible Poly(ADP-ribose) Polymerase (TIPARP, PARP7; NCBI gene ID: 25976) T-cell immune receptors with Ig and ITIM domains (TIGIT; NCBI gene ID: 201633); Trigger receptor 1 for bone marrow cell expression (TREM1; NCBI gene ID: 54210); Trigger receptor 2 for bone marrow cell expression (TREM2; NCBI gene ID: 54209); Tumor-associated calcium signaling transducers 2 (TACSTD2, TROP2, EGP1; NCBI gene ID: 4070); Tumor necrosis factor receptor superfamily member 4 (TNFRSF4, CD134, OX40; NCBI gene ID: 7293); Tumor necrosis factor receptor superfamily member 9 (TNFRSF9, 4-1BB, CD137; NCBI gene ID: 3604); Tumor necrosis factor receptor superfamily member 18 (TNFRSF18, CD357, GITR; NCBI gene ID: 8784).WRN-based RecQ helicases (WRN; NCBI gene ID: 7486); or zinc finger proteins Helios (IKZF2; NCBI gene ID: 22807). Explanatory Mechanism of Action: Immune Checkpoint Modulators In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, are administered together with one or more inhibitory immune checkpoint proteins or receptors as blockers or inhibitors and / or with one or more stimulators, activators, or agonists of one or more stimulating immune checkpoint proteins or receptors. Blocking or inhibiting inhibitory immune checkpoints can positively regulate T cell or NK cell activation and prevent cellular immune escape within the tumor microenvironment. Activation or stimulation of stimulating immune checkpoints can amplify the effects of immune checkpoint inhibitors in cancer therapeutics. In some embodiments, immune checkpoint proteins or receptors regulate T cell responses (e.g., as reviewed in Xu, ...). et al., J Exp Clin Cancer Res. (2018) 37:110. In some embodiments, immune checkpoint proteins or receptors regulate NK cell responses (e.g., reviewed in Davis, et al., Semin Immunol. (2017) 31:64–75 and Chiossone, et al., Nat Rev Immunol. (2018) 18(11):671-688. Regulation of T cell (Treg) suppression or Treg elimination can alleviate the suppression of anti-tumor immune responses and has anti-cancer effects (e.g., a review in Plitas and Rudensky, Annu. Rev. Cancer Biol. (2020) 4:459-77; Tanaka and Sakaguchi, Eur. J. Immunol. (2019) 49:1140-1146). Examples of immune checkpoint proteins or receptors that can be combined with the compounds provided herein or their pharmaceutically acceptable salts include CD27 (NCBI gene ID: 939), CD70 (NCBI gene ID: 970); CD40 (NCBI gene ID: 958), CD40LG (NCBI gene ID: 959); CD47 (NCBI gene ID: 961), SIRPA (NCBI gene ID: 140885); CD48 (SLAMF2; NCBI gene ID: 962), and transmembrane and immunoglobulin domain 2 (TM). IGD2, CD28H; NCBI gene ID: 126259), CD84 (LY9B, SLAMF5; NCBI gene ID: 8832), CD96 (NCBI gene ID: 10225), CD160 (NCBI gene ID: 11126), MS4A1 (CD20; NCBI gene ID: 931), CD244 (SLAMF4; NCBI gene ID: 51744); CD276 (B7H3; NCBI gene ID: 80381); V-set domain-containing T cell activation repressor 1 (VTCN1, B7H4); V-set immunomodulatory receptors (VSIR, B7H5, VISTA; NCBI gene ID: 64115); Immunoglobulin superfamily member 11 (IGSF11, VSIG3; NCBI gene ID: 152404); Natural killer cell cytotoxic receptor 3 ligand 1 (NCR3LG1, B7H6; NCBI gene ID: 374383); HERV-H LTR-associated 2 (HHLA2, B7H7; NCBI gene ID: 11148); Inducible T cell costimulators (ICOS, CD278; NCBI gene ID: 29851); Inducible T cell costimulator ligands (ICOSLG, B7H2; NCBI gene ID: 23308); TNF receptor superfamily member 4 (TNFRSF4, OX40; NCBI gene ID: 7293); TNF superfamily member 4 (TNFSF4, OX40L; NCBI gene ID: 7292); TNFRSF8 (CD30; NCBI gene ID: 943), T NFSF8 (CD30L; NCBI gene ID: 944); TNFRSF10A (CD261, DR4, TRAILR1; NCBI gene ID: 8797), TNFRSF9 (CD137; NCBI gene ID: 3604), TNFSF9 (CD137L; NCBI gene ID: 8744); TNFRSF10B (CD262, DR5, TRAILR2; NCBI gene ID: 8795), TNFRSF10 (TRAIL; NCBI gene ID: 8743); TNFRSF14 (HVEM, CD270);NCBI gene ID: 8764), TNFSF14 (HVEML; NCBI gene ID: 8740); CD272 (B and T lymphocyte-associated (BTLA); NCBI gene ID: 151888); TNFRSF17 (BCMA, CD269; NCBI gene ID: 608), TNFSF13B (BAFF; NCBI gene ID: 10673); TNFRSF18 (GITR; NCBI gene ID: 8784), TNFSF18 (GITRL; NCBI gene ID: 8995); MHC type I polypeptide-associated sequence A (MICA; NCBI gene ID: 100507436); MHC type I polypeptide-associated sequence B (MICB; NCBI gene ID: 4277); CD274 (CD274, PDL1, PD-L1; NCBI gene ID: 29126); programmed cell death 1 (PD-L1); CD1, PD1, PD-1; NCBI gene ID: 5133); cytotoxic T-lymphocyte-associated protein 4 (CTLA4, CD152; NCBI gene ID: 1493); CD80 (B7-1; NCBI gene ID: 941), CD28 (NCBI gene ID: 940); connexin cell adhesion molecule 2 (NECTIN2, CD112; NCBI gene ID: 5819); CD226 (DNAM-1; NCBI gene ID: 10666); poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155; NCBI gene ID: 5817); containing PVR-associated immunoglobulin domain (PVRIG, CD112R; NCBI gene ID: 79037); T-cell immune receptor with Ig and ITIM domains (TIGIT; NCBI gene ID: 201633); containing T-cell immunoglobulin and mucin domain 4 (TIMD4; TIM4; NCBI gene ID: 91937); Hepatitis A virus cellular receptor 2 (HAVCR2, TIMD3, TIM3; NCBI gene ID: 84868); Galactoglobulin 9 (LGALS9; NCBI gene ID: 3965); Lymphocyte activation 3 (LAG3, CD223; NCBI gene ID: 3902); Messenger lymphocyte activation molecule family member 1 (SLAMF1, SLAM, CD150; NCBI gene ID: 6504); Lymphocyte antigen 9 (LY9, CD229, SLAMF3; NCBI gene ID: 4063); SLAM family member 6 (SLAMF6, CD352; NCBI gene ID: 114836); SLAM family member 7 (SLAMF7, CD319; NCBI gene ID: 57823); UL16 binding protein 1 (ULBP1; NCBI gene ID: 80329);UL16-binding protein 2 (ULBP2; NCBI gene ID: 80328); UL16-binding protein 3 (ULBP3; NCBI gene ID: 79465); early retinoic acid transcript 1E (RAET1E; ULBP4; NCBI gene ID: 135250); early retinoic acid transcript 1G (RAET1G; ULBP5; NCBI gene ID: 353091); early retinoic acid transcript 1L (RAET1L; ULBP6; NCBI gene ID: 154064); killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 1 (KIR, CD158E1; NCBI gene ID: 3811, e.g., lirelirumab (IPH-2102, IPH-4102); Killer cell lectin-like receptor C1 (KLRC1, NKG2A, CD159A; NCBI gene ID: 3821); Killer cell lectin-like receptor K1 (KLRK1, NKG2D, CD314; NCBI gene ID: 22914); Killer cell lectin-like receptor C2 (KLRC2, CD159c, NKG2C; NCBI gene ID: 3822); Killer cell lectin-like receptor C3 (KLRC3, NKG2E; NCBI gene ID: 3823); Killer cell lectin-like receptor C4 (KLRC4, NKG2F; NCBI gene ID: 8302); Killer cell immunoglobulin-like receptor, two Ig domains, and long cytoplasmic tail 1 (KIR2DL1; NCBI gene ID: 3802); Killer cell immunoglobulin-like receptor, two Ig domains, and long cytoplasmic tail 2 (KIR2DL2; NCBI gene ID: 3803); Killer cell immunoglobulin-like receptor, two Ig domains, and long cytoplasmic tail 3 (KIR2DL3; NCBI gene ID: 3804); Killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 1 (KIR3DL1); Killer cell lectin-like receptor D1 (KLRD1; NCBI gene ID: 3824); Killer cell lectin-like receptor G1 (KLRG1; CLEC15A, MAFA, 2F1; NCBI gene ID: 10219); Sialic acid-binding Ig-like lectin 7 (SIGLEC7; NCBI gene ID: 27036); and Sialic acid-binding Ig-like lectin 9 (SIGLEC9; NCBI gene ID: 27180). In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with one or more blockers or inhibitors of one or more T-cell suppressive immune checkpoint proteins or receptors. Exemplary T-cell suppressor immune checkpoint proteins or receptors include CD274 (CD274, PDL1, PD-L1); programmed cell death 1 ligand 2 (PDCD1LG2, PD-L2, CD273); programmed cell death 1 (PDCD1, PD1, PD-1); cytotoxic T-lymphocyte-associated protein 4 (CTLA4, CD152); CD276 (B7H3); V-set domain-containing T-cell activation inhibitor 1 (VTCN1, B7H4); V-set immunomodulatory receptors (VSIR, B7H5, VISTA); immunoglobulin superfamily member 11 (IGSF11, VSIG3); TNFRSF14 (HVEM, CD270), TNFSF14 (HVEML); CD272 (B and T lymphocyte-associated (BTLA)); and PVR-containing immunoglobulin domain-containing (PVRIG, CD112R); T-cell immune receptor with Ig and ITIM domains (TIGIT); lymphocyte activation 3 (LAG3, CD223); hepatitis A virus cellular receptor 2 (HAVCR2, TIMD3, TIM3); galactoglobulin 9 (LGALS9); killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 1 (KIR, CD158E1); killer cell immunoglobulin-like receptor, two Ig domains, and long cytoplasmic tail 1 (KIR2DL1); killer cell immunoglobulin-like receptor, two Ig domains, and long cytoplasmic tail 2 (KIR2DL2); killer cell immunoglobulin-like receptor, two Ig domains, and long cytoplasmic tail 3 (KIR2DL3); and killer cell immunoglobulin-like receptor, three Ig domains, and long cytoplasmic tail 1 (KIR3DL1). In some embodiments, the compounds provided herein or their pharmaceutically acceptable salts are administered together with one or more agonists or activators of one or more T-cell stimulating immune checkpoint proteins or receptors.Illustrative T-cell stimulating immune checkpoint proteins or receptors include, but are not limited to, CD27, CD70; CD40, CD40LG; inducible T-cell costimulators (ICOS, CD278); inducible T-cell costimulator ligands (ICOSLG, B7H2); TNF receptor superfamily member 4 (TNFRSF4, OX40); TNF superfamily member 4 (TNFSF4, OX40L); TNFRSF9 (CD137), TNFSF9 (CD137L); TNFRSF18 (GITR), TNFSF18 (GITRL); CD80 (B7-1), CD28; connexin cell adhesion molecule 2 (NECTIN2, CD112); CD226 (DNAM-1); CD244 (2B4, SLAMF4); poliovirus receptor (PVR) cell adhesion molecule (PVR, CD155). See, for example, Xu. et al., J Exp Clin Cancer Res. (2018) 37:110. In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with one or more blockers or inhibitors of one or more NK cell inhibitory immune checkpoint proteins or receptors. Exemplary NK cell inhibitory immune checkpoint proteins or receptors include killer cell immunoglobulin-like receptors (KIRs), with three Ig domains and a long cytoplasmic tail 1 (KIR, CD158E1); killer cell immunoglobulin-like receptors (KIRs), with two Ig domains and a long cytoplasmic tail 1 (KIR2DL1); killer cell immunoglobulin-like receptors (KIRs), with two Ig domains and a long cytoplasmic tail 2 (KIR2DL2); killer cell immunoglobulin-like receptors (KIRs), with two Ig domains and a long cytoplasmic tail 3 (KIR2DL3); killer cell immunoglobulin-like receptors (KIRs), with three Ig domains and a long cytoplasmic tail 1 (KIR3DL1); killer cell lectin-like receptor C1 (KLRC1, NKG2A, CD159A); killer cell lectin-like receptor D1 (KLRD1, CD94); killer cell lectin-like receptor G1 (KLRG1; CLEC15A, MAFA, 2F1); and sialic acid-binding Ig-like lectin 7. (SIGLEC7); and sialic acid-binding Ig-like lectin 9 (SIGLEC9). In some embodiments, the compounds provided herein or their pharmaceutically acceptable salts are administered together with one or more agonists or activators of one or more NK cell-stimulating immune checkpoint proteins or receptors. Exemplary NK cell-stimulating immune checkpoint proteins or receptors include CD16, CD226 (DNAM-1); CD244 (2B4, SLAMF4); killer cell lectin-like receptor K1 (KLRK1, NKG2D, CD314); and SLAM family member 7 (SLAMF7). See, for example, Davis, et al., Semin Immunol. (2017) 31:64–75; Fang, et al., Semin Immunol. (2017) 31:37-54; and Chiossone, et al., Nat Rev Immunol. (2018) 18(11):671-688. In some embodiments, one or more immune checkpoint inhibitors comprise inhibitors of proteins (e.g., antibodies or fragments thereof, or antibody mimics) of PD-L1 (CD274), PD-1 (PDCD1), CTLA4, or TIGIT. In some embodiments, one or more immune checkpoint inhibitors comprise inhibitors of small organic molecules of PD-L1 (CD274), PD-1 (PDCD1), CTLA4, or TIGIT. In some embodiments, one or more immune checkpoint inhibitors comprise inhibitors of proteins (e.g., antibodies or fragments thereof, or antibody mimics) of LAG3. Examples of co-administerable CTLA4 inhibitors include ipilimumab, trimemumab, BMS-986218, AGEN1181, zalifrelimab (AGEN1884), BMS-986249, MK-1308, REGN-4659, ADU-1604, CS-1002 (ipilimumab biosimilar), BCD-145, APL-509, JS-007, BA-3071, ONC-392, AGEN-2041, HBM-4003, JHL-1155, KN-044, CG-0161, ATOR-1144, PBI-5D3H5, BPI-002, and multispecific inhibitors FPT-155 (CTLA4 / PD-L1 / CD28) and PF-06936308 (PD-1 / CTLA4), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), XmAb-20717 (PD-1 / CTLA4), and AK-104 (CTLA4 / PD-1). Examples of co-administerable PD-L1 (CD274) or PD-1 (PDCD1) inhibitors include pembrolizumab, nivolumab, cemiplimab, pidilizumab, AMP-224, MEDI0680 (AMP-514), spartalizumab, atezolizumab, avelumab, durvalumab, BMS-936559, cosibelimab (CK-301), sasanlimab (PF-06801591), tislelizumab (BGB-A317), GLS-010 (WBP-3055), and AK-103. (HX-008), AK-105, CS-1003, HLX-10, retifanlimab (MGA-012), BI-754091, balstilimab (AGEN-2034), AMG-404, toripalimab (JS-001), cetrelimab (JNJ-63723283), genolimzumab (CBT-501), LZM-009, prolgolimab (BCD-100), lodapolimab (LY-3300054), SHR-1201, camrelizumab (SHR-1210), Sym-021, budigalimab (ABBV-181), PD1-PIK, BAT-1306, avelumab (MSB0010718C), CX-072, CBT-502, dostarlimab (TSR-042), MSB-2311, JTX-4014, BGB-A333, SHR-1316, CS-1001 (WBP-3155), envafolimab (KN-035), sintilimab (IBI-308), HLX-20, KL-A167, STI-A1014, STI-A1015(IMC-001), BCD-135, FAZ-053, TQB-2450, MDX1105-01, GS-4224, GS-4416, INCB086550, MAX10181, zimberelimab (AB122), spartalizumab (PDR-001), and compounds disclosed in WO2018195321, WO2020014643, WO2019160882, or WO2018195321, as well as multispecific inhibitors FPT-155 (CTLA4 / PD-L1 / CD28), PF-06936308 (PD-1 / CTLA4), MGD-013 (PD-1 / LAG-3), FS-118 (LAG-3 / PD-L1), RO-7247669 (PD-1 / LAG-3), MGD-019 (PD-1 / CTLA4), KN-046 (PD-1 / CTLA4), MEDI-5752 (CTLA4 / PD-1), RO-7121661 (PD-1 / TIM-3), RG7769 (PD-1 / TIM-3), TAK-252 (PD-1 / OX40L), (PD-L1 / 4-1BB), bintrafusp α) (M7824; PD-L1 / TGFβ-EC domain), CA-170 (PD-L1 / VISTA), CDX-527 (CD27 / PD-L1), LY-3415244 (TIM3 / PDL1), and INBRX-105 (4-1BB / PDL1). In some embodiments, the PD-L1 inhibitor is a small molecule inhibitor, such as CA-170, GS-4224, GS-4416, and lazertinib (GNS-1480; PD-L1 / EGFR). Examples of TIGIT inhibitors that can be co-administered include tiragolumab (RG-6058), vibostolimab, domvanalimab (AB154), AB308, BMS-986207, AGEN-1307, COM-902, or etigilimab. Examples of LAG3 inhibitors that can be co-administered include leramilimab (LAG525). Inhibiting regulatory T cell (Treg) activity or eliminating Tregs can reduce the suppression of anti-tumor immune responses and has anti-cancer effects. See, for example, Plitas and Rudensky. Annu. Rev. Cancer Biol. (2020) 4:459-77; Tanaka and Sakaguchi, Eur. J. Immunol. (2019) 49:1140-1146. In some embodiments, compounds of formulas (I), (Ia), (Ib), or (Ic) provided herein, or their pharmaceutically acceptable salts provided herein, are administered together with one or more inhibitors of Treg activity or Treg eliminators. Treg inhibition or elimination can amplify the effects of immune checkpoint inhibitors in cancer therapeutics. In some embodiments, the compounds provided herein or their pharmaceutically acceptable salts are administered together with one or more Treg inhibitors. In some embodiments, the Treg inhibitors inhibit the migration of Tregs into the tumor microenvironment. In some embodiments, the Treg inhibitors reduce the immunosuppressive function of Tregs. In some embodiments, the Treg inhibitors modulate cell phenotype and induce the production of pro-inflammatory interferons. Exemplary Treg inhibitors include, but are not limited to, CCR4 (NCBI gene ID: 1233) antagonists and the following degraders: Ikaros zinc finger proteins (e.g., Ikaros (IKZF1; NCBI gene ID: 10320), Helios (IKZF2; NCBI gene ID: 22807), Aiolos (IKZF3; NCBI gene ID: 22806), and Eos (IKZF4; NCBI gene ID: 64375). Examples of co-dispensable Helios degrading agents include, but are not limited to, I-57 (Novartis) and the compounds disclosed in the following: WO2019038717, WO2020012334, WO20200117759, and WO2021101919. In some embodiments, the compounds provided herein or their pharmaceutically acceptable salts are administered together with one or more Treg eradicators. In some embodiments, the Treg eradicator is an antibody. In some embodiments, the Treg eradicator antibody has antibody-dependent cytotoxic (ADCC) activity. In some embodiments, the Treg eradicator antibody system is Fc engineered to enhance ADCC activity. In some embodiments, the Treg eradicator antibody system is an antibody-drug conjugate (ADC). Indicative targets of Treg eradicators include, but are not limited to, CD25 (IL2RA; NCBI gene ID: 3559), CTLA4 (CD152; NCBI gene ID: 1493); GITR (TNFRSF18; NCBI gene ID: 8784); 4-1BB (CD137; NCBI gene ID: 3604), OX-40 (CD134; NCBI gene ID: 7293), LAG3 (CD223; NCBI gene ID: 3902), TIGIT (NCBI gene ID: 201633), CCR4 (NCBI gene ID: 1233), and CCR8 (NCBI gene ID: 1237). In some embodiments, the co-administerable Treg inhibitor or Treg eradicator comprises an antibody or antigen-binding fragment thereof that selectively binds to a cell surface receptor selected from the group consisting of: CC motif chemokine receptor 4 (CCR4), CC motif chemokine receptor 7 (CCR7), CC motif chemokine receptor 8 (CCR8), CXC motif chemokine receptor 4 (CXCR4; CD184), TNFRSF4 (OX40), TNFRSF18 (GITR, CD357), TNFRSF9 (4-1BB, CD137), cytotoxic T lymphocyte-associated protein 4 (CTLA4, CD152), programmed cell death 1 (PDCD1, PD-1), sialylated Lewis x (CD15s), CD27, extracellular nucleoside triphosphate diphosphate hydrolase 1 (ENTPD1; CD39), protein tyrosine phosphatase receptor type C (PTPRC; CD45), neural cell adhesion molecule 1 (NCAM1; CD56), selectin L (SELL; CD62L), integrin subunit αE (ITGAE; CD103), interleukin-7 receptor (IL7R; CD127), CD40 ligand (CD40LG; CD154), folate receptor α (FOLR1), folate receptor β (FOLR2), leucine-rich repeat 32 (LRRC32; GARP), IKAROS family zinc finger 2 (IKZF2; HELIOS), inducible T cell costimulator (ICOS; CD278), lymphocyte activation 3 (LAG3; CD223), transforming growth factor β1 (TGFB1), hepatitis A virus cellular receptor 2 (HAVCR2; CD366; TIM3), T cell immune receptor with Ig and ITIM domains (TIGIT), TNF receptor superfamily member 1B (CD120b; TNFR2), IL2RA (CD25), or combinations thereof. Examples of Tregs that can be administered to eliminate anti-CCR8 antibodies include, but are not limited to, JTX-1811 (GS-1811) (Jounce Therapeutics, Gilead Sciences), BMS-986340 (Bristol Meyers Squibb), S-531011 (Shionogi), FPA157 (Five Prime Therapeutics), SRF-114 (Surface Oncology), HBM1022 (Harbor BioMed), IO-1 (Oncurious), and antibodies disclosed in WO2021163064, WO2020138489, and WO2021152186. Examples of Treg-specific anti-CCR4 antibodies that can be administered include moglicillinumab. Inhibiting, eliminating, or reprogramming non-stimulatory bone marrow cells in the tumor microenvironment can enhance anti-cancer immune responses (see, for example, Binnewies). et al., Nat. Med. (2018) 24(5):541-550; WO2016049641. Exemplary targets for the elimination or reprogramming of non-stimulated myeloid cells include the trigger receptors TREM-1 (CD354, NCBI gene ID: 54210) and TREM-2 (NCBI gene ID: 54209) that trigger myeloid cell expression. In some embodiments, the compounds provided herein or their pharmaceutically acceptable salts are administered together with one or more myeloid cell elimination or reprogramming agents, such as anti-TREM-1 antibodies (e.g., PY159; disclosed in WO2019032624) or anti-TREM-2 antibodies (e.g., PY314; disclosed in WO2019118513). Differentiation cluster agonists or activators. In some embodiments, compounds of formulas (I), (Ia), (Ib), or (Ic) provided herein, or their pharmaceutically acceptable salt derivatives, are administered together with agents targeting differentiation cluster (CD) markers. Examples of co-administerable CD markers include, but are not limited to, A6, AD-IL24, neratinib, tucatinib (ONT 380), mobocertinib (TAK-788), tesevatinib, trastuzumab (HERCEPTIN®), trastuzumab biosimilar (HLX-02), margetuximab, BAT-8001, pertuzumab (Perjeta), pegfilgrastim, RG6264, zanidatamab (ZW25), cavatak, AIC-100, and tagraxofusp. (SL-401), HLA-A2402 / HLA-A0201 restricted epitope peptide vaccine, dasatinib, imatinib, nilotinib, sorafenib, lenvatinib mesylate, ofranergene Obadenovec, cabozantinib malate, AL-8326, ZLJ-33, KBP-7018, sunitinib malate, pazopanib derivative, AGX-73, rebastinib, NMS-088, lucitinib hydrochloride, midostaurin, cediranib, dovitinib, sitravatinib, tivozanib, masitinib, regorafenib, olverembatinib dimethyl sulfonate (HQP-1351), cabozantinib, ponatinib, and famitinib L-malate, CX-2029 (ABBV-2029), SCB-313, CA-170, COM-701, CDX-301, GS-3583, asunercept(APG-101), APO-010, Compounds shown in the lower row: WO2016196388, WO2016033570, WO2015157386, WO199203459, WO199221766, WO 2004080462, WO2005020921, WO2006009755, WO2007078034, WO2007092403, WO2007127317, WO2008005877, WO20121 54480, WO2014100620, WO2014039714, WO2015134536, WO2017167182, WO2018112136, WO2018112140, WO201915506 7, WO2020076105, PCT / US2019 / 063091, WO19173692, WO2016179517, WO2017096179, WO2017096182, WO2017096281, WO2018089628, WO2017096179, WO2018089628, WO2018195321, WO2020014643, WO2019160882, WO2018195321, WO20 0140307, ​​WO2002092784, WO2007133811, WO2009046541, WO2010083253, WO2011076781, WO2013056352, WO20151386 00, WO2016179399, WO2016205042, WO2017178653, WO2018026600, WO2018057669, WO2018107058, WO2018190719, W O2018210793, WO2019023347, WO2019042470, WO2019175218, WO2019183266, WO2020013170, WO2020068752, Cancer Discov. 2019 Jan 9(1):8; and Gariepy J., et al. 106th Annu Meet Am Assoc Immunologists (AAI) (May 9-13, San Diego, 2019, Abst 71.5). In some embodiments, co-administerable CD-labeled targets include small molecule inhibitors such as PBF-1662, BLZ-945, pemigatinib (INCB-054828), rogaratinib (BAY-1163877), AZD4547, roblitinib (FGF-401), quizartinib dihydrochloride, SX-682, AZD-5069, PLX-9486, avapritinib (BLU-285), and ripretinib. (DCC-2618), Imatinib Mesylate, JSP-191, BLU-263, CD117-ADC, AZD3229, Telatinib, Vorolanib, GO-203-2C, AB-680, PSB-12379, PSB-12441, PSB-12425, CB-708, HM-30181A, Motixafortide (BL-8040), LY2510924, Burixafor (TG-0054), X4P-002, Mavorixafor (X4P-001-IO), Plerixafor, CTX-5861, and REGN-5678 (PSMA / CD28). In some embodiments, co-administerable CD-labeled targeting agents include small molecule agonists such as interleukin-2 receptor subunit γ, eltrombopag, rintatolimod, poly-ICLC (NSC-301463), Riboxxon, Apoxxim, RIBOXXIM®, MCT-465, MCT-475, G100, PEPA-10, eftozanermin alfa (ABBV-621), E-6887, motolimod, resiquimod, and selgantolimod. (GS-9688), VTX-1463, NKTR-262, AST-008, CMP-001, cobitolimod, tilsotolimod, litenimod, MGN-1601, BB-006, IMO-8400, IMO-9200, agatolimod, DIMS-9054, DV-1079, lefitolimod (MGN-1703), CYT-003, and PUL-042. In some embodiments, co-administerable CD-labeled targets include antibodies such as tafasitamab (MOR208; MorphoSys AG), inebilizumab (MEDI-551), obinutuzumab, IGN-002, rituximab biosimilar (PF-05280586), varlilumab (CDX-1127), AFM-13 (CD16 / CD30), AMG330, otlertuzumab (TRU-016), isatuximab, felzartamab (MOR-202), TAK-079, TAK573, and daratumumab. (DARZALEX®), TTX-030, selicrelumab (RG7876), APX-005M, ABBV-428, ABBV-927, mitazalimab (JNJ-64457107), lenziluma, alemtuzuma, emactuzumab, AMG-820, FPA-008 (cabiralizumab), PRS-343 (CD-137 / Her2), AFM-13 (CD16 / CD30), belantamab mafodotin (GSK-2857916), AFM26 (BCMA / CD16A), simlukafusp alfa (RG7461), urelumab, utomilumab (PF-05082566), AGEN2373, ADG-106, BT-7480, PRS-343 (CD-137 / HER2), FAP-4-IBBL (4-1BB / FAP), ramucirumab, CDX-0158, CDX-0159 and FSI-174, relatlimab (ONO-4482), LAG-525, MK-4280, fianlimab (REGN-3767), INCAGN2385, encelimab (TSR-033), atipotuzumab, BrevaRex (Mab-AR-20).5) MEDI-9447 (oleclumab), CPX-006, IPH-53, BMS-986179, NZV-930, CPI-006, PAT-SC1, lirilumab (IPH-2102), lacutamab (IPH-4102), monalizumab, BAY-1834942, NEO-201 (CEACAM 5 / 6), apamistamab (131I-BC8) (lomab-B), MEDI0562 (tavolixizumab), GSK-3174998, INCAGN1949, BMS-986178, GBR-8383, ABBV-368, denosumab, BION-1301, MK-4166, INCAGN-1876, TRX-518, BMS-986156, MK-1248, GWN-323, CTB-006, INBRX-109, GEN-1029, pepinemab (VX-15), vopratelimab (JTX-2011), GSK3359609, cobolimab (TSR-022), MBG-453, INCAGN-2390, and the compounds disclosed in WO2017096179, WO2017096276, WO2017096189, and WO2018089628. In some embodiments, co-administerable CD-labeled targets include cell therapies such as CD19-ARTEMIS, TBI-1501, CTL-119 huCART-19 T cells, lisocabtagene maraleucel (JCAR-017), axicabtagene ciloleucel (KTE-C19, Yescarta®), cisagenlecleucel (KTE-X19), US7741465, US6319494, UCART-19, tabelecleucel (EBV-CTL), tisagenlecleucel-T (CTL019), CD19CAR-CD28-CD3ζ-EGFRt-expressive T cells, and CD19 / 4-1BBL armed CAR. T-cell therapy, C-CAR-011, CIK-CAR.CD19, CD19CAR-28-ζ T-cell, PCAR-019, MatchCART, DSCAR-01, IM19 CAR-T, TC-110, anti-CD19 CAR T-cell therapy (B-cell acute lymphoblastic leukemia, Universiti Kebangsaan Malaysia), anti-CD19 CAR T-cell therapy (acute lymphoblastic leukemia / non-Hodgkin's lymphoma, University Hospital Heidelberg), anti-CD19 CAR T-cell therapy (silent IL-6 manifested cancer, Shanghai Unicar-Therapy Bio-medicine Technology), MB-CART2019.1 (CD19 / CD20), GC-197 (CD19 / CD7), CLIC-1901, ET-019003, anti-CD19-STAR-T cells, AVA-001, BCMA-CD19 cCAR (CD19 / APRIL), ICG-134, ICG-132 (CD19 / CD20), CTA-101, WZTL-002, dual anti-CD19 / anti-CD20 CAR T cells (chronic lymphocytic leukemia / B-cell lymphoma), HY-001, ET-019002, YTB-323, GC-012 (CD19 / APRIL), GC-022 (CD19 / CD22), CD19CAR-CD28-CD3ζ-EGFRt expression Tn / mem, UCAR-011, ICTCAR-014, GC-007F, PTG-01, CC-97540, GC-007G, TC-310, GC-197, Tezazaneluse-T, CART-19, Tezazaneluse (CTL-019)), anti-CD20 CAR T-cell therapy (non-Hodgkin's lymphoma), MB-CART2019.1 (CD19 / CD20), WZTL-002 dual anti-CD19 / anti-CD20 CAR-T cells, ICG-132 (CD19 / CD20), ACTR707 ATTCK-20, PBCAR-20A, LB-1905, CIK-CAR, CD33, CD33CART, dual anti-BCMA / anti-CD38 CAR T-cell therapy, CART-ddBCMA, MB-102, IM-23, JEZ-567, UCART-123, PD-1 knockout T-cell therapy (esophageal cancer / NSCLC), ICTCAR-052, Tn MUC-1 CAR-T, ICTCAR-053, PD-1 knockout T-cell therapy (esophageal cancer / NSCLC), AUTO-2, anti-BCMA CAR T-cell therapy, Descartes-011, anti-BCMA / anti-CD38 CAR T-cell therapy, CART-ddBCMA, BCMA-CS1 cCAR, CYAD-01 (NKG2D ligand modulator), KD-045, PD-L1 t-haNK, BCMA-CS1 cCAR, MEDI5083, anti-CD276 CART, and therapies disclosed in WO2012079000 or WO2017049166. Differentiation clusters. 47 (CD47) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIIa), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), or (IVa-2), or their pharmaceutically acceptable salts, provided herein, are administered together with an inhibitor of CD47 (IAP, MER6, OA3; NCBI gene ID: 961). Examples of CD47 inhibitors include anti-CD47 mAb (Vx-1004), anti-human CD47 mAb (CNTO-7108), CC-90002, CC-90002-ST-001, humanized anti-CD47 antibodies or CD47 blockers, NI-1701, NI-1801, RCT-1938, ALX148, SG-404, SRF-231, and TTI-621.Additional illustrative anti-CD47 antibodies include CC-90002, magrolimab (Hu5F9-G4), AO-176 (Vx-1004), letaplimab (IBI-188), and lemzoparlimab. (TJC-4), SHR-1603, HLX-24, LQ-001, IMC-002, ZL-1201, IMM-01, B6H12, GenSci-059, TAY-018, PT-240, 1F8-GMCSF, SY-102, KD-015, ALX-148, AK-117, TTI-621, TTI-622, or disclosed in WO199727873, WO199940940, WO2002092784, WO2005044857, WO200904654 1. WO2010070047, WO2011143624, WO2012170250, WO2013109752, WO2013119714, WO2014087248, WO2015191861, WO20160229 71. WO2016023040, WO2016024021, WO2016081423, WO2016109415, WO2016141328, WO2016188449, WO2017027422, WO2017049 251. WO2017053423, WO2017121771, WO2017194634, WO2017196793, WO2017215585, WO2018075857, WO2018075960, WO201808 9508, WO2018095428, WO2018137705, WO2018233575, WO2019027903, WO2019034895, WO2019042119, WO2019042285, WO20190 Compounds in WO22470, WO2019086573, WO2019108733, WO2019138367, WO2019144895, WO2019157843, WO2019179366, WO2019184912, WO2019185717, WO2019201236, WO2019238012, WO2019241732, WO2020019135, WO2020036977, WO2020043188, and WO2020009725.In some embodiments, the CD47 inhibitor is RRx-001, DSP-107, VT-1021, IMM-02, SGN-CD47M, or SIRPa-Fc-CD40L (SL-172154). In some embodiments, the CD47 inhibitor is maguromab. In some embodiments, CD47 inhibitors are bispecific antibodies targeting CD47, such as IBI-322 (CD47 / PD-L1), IMM-0306 (CD47 / CD20), TJ-L1C4 (CD47 / PD-L1), HX-009 (CD47 / PD-1), PMC-122 (CD47 / PD-L1), PT-217 (CD47 / DLL3), IMM-26011 (CD47 / FLT3), IMM-0207 (CD47 / VEGF), IMM-2902 (CD47 / HER2), BH29xx (CD47 / PD-L1), IMM-03 (CD47 / CD20), IMM-2502 (CD47 / PD-L1), HMBD-004B (CD47 / BCMA), HMBD-004A (CD47 / CD33), TG-1801 (NI-1701), or NI-1801. SIRPa Target Agent In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or their pharmaceutically acceptable salts, provided herein, are administered together with the SIRPa target agent (NCBI gene ID: 140885; UniProt P78324). Examples of co-administerable SIRPa-targeting agents include SIRPa inhibitors such as AL-008, RRx-001, and CTX-5861, and anti-SIRPa antibodies such as FSI-189 (GS-0189), ES-004, BI-765063, ADU1805, CC-95251, and Q-1801 (SIRPa / PD-L1). Additional SIRPα-targeting agents used are described in, for example, WO200140307, ​​WO2002092784, WO2007133811, WO2009046541, WO2010083253, WO2011076781, WO2013056352, WO2015138600, WO2016179399, WO2016205042, and WO20 17178653, WO2018026600, WO2018057669, WO2018107058, WO2018190719, WO2018210793, WO2019023347, WO2019042470, WO2019175218, WO2019183266, WO2020013170, and WO2020068752. FLT3R agonist In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, are administered together with an FLT3R agonist. In some embodiments, compounds of formulas (Ia), (IIb), or pharmaceutically acceptable salts thereof, are administered together with an FLT3 ligand. In some embodiments, compounds of formulas (Ia), (IIb), or pharmaceutically acceptable salts thereof, are administered together with, for example, the FLT3L-Fc fusion protein described in WO2020263830. In some embodiments, the compounds provided herein, or pharmaceutically acceptable salts thereof, are administered together with GS-3583 or CDX-301. In some embodiments, the compounds provided herein, or pharmaceutically acceptable salts thereof, are administered together with GS-3583. TNF receptor superfamily (TNFRSF) member agonists or activators In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with agonists of one or more members of the TNF receptor superfamily (TNFRSF), such as one or more of the following agonists: TNFRSF1A (NCBI gene ID: 7132), TNFRSF1B (NCBI gene ID: 7133), TNFRSF4 (OX40, CD134; NCBI gene ID: 7293), TNFRSF5 (CD40;TNFRSF10A (CD27, NCBI gene ID: 958), TNFRSF6 (FAS, NCBI gene ID: 355), TNFRSF7 (CD27, NCBI gene ID: 939), TNFRSF8 (CD30, NCBI gene ID: 943), TNFRSF9 (4-1BB, CD137, NCBI gene ID: 3604), TNFRSF10A (CD261, DR4, TRAILR1, NCBI gene ID: 8797), TNFRSF10B (CD262, DR5, TRAILR2, NCBI gene ID: 8795), TNFRSF10C (CD263, TRAILR3, NCBI gene ID: 8794), TNFRSF10D (CD264, TRAILR4, NCBI gene ID: 8793), TNFRSF11A (CD265, RANK ... TNFRSF11B (NCBI gene ID: 4982), TNFRSF12A (CD266, NCBI gene ID: 51330), TNFRSF13B (CD267, NCBI gene ID: 23495), TNFRSF13C (CD268, NCBI gene ID: 115650), TNFRSF16 (NGFR, CD271, NCBI gene ID: 4804), TNFRSF17 (BCMA, CD269, NCBI gene ID: 608), TNFRSF18 (GITR, CD357, NCBI gene ID: 8784), TNFRSF19 (NCBI gene ID: 55504), TNFRSF21 (CD358, DR6, NCBI gene ID: 27242), and TNFRSF25 (DR3, NCBI gene ID: 8718). Examples of co-administerable anti-TNFRSF4 (OX40) antibodies include MEDI6469, MEDI6383, tavolicimab (MEDI0562), MOXR0916, PF-04518600, RG-7888, GSK-3174998, INCAGN1949, BMS-986178, GBR-8383, ABBV-368, and those described in WO2016179517, WO2017096179, WO2017096182, WO2017096281, and WO2018089628. Examples of co-administerable anti-TNFRSF5 (CD40) antibodies include RG7876, SEA-CD40, APX-005M, and ABBV-428. In some embodiments, the anti-TNFRSF7 (CD27) antibody varlilumab (CDX-1127) can be co-administered. Examples of co-administerable anti-TNFRSF9 (4-1BB, CD137) antibodies include urelumab, utomilumab (PF-05082566), AGEN-2373, and ADG-106. In some embodiments, the anti-TNFRSF17 (BCMA) antibody GSK-2857916 was co-administered. Examples of co-administerable anti-TNFRSF18 (GITR) antibodies include MEDI1873, FPA-154, INCAGN-1876, TRX-518, BMS-986156, MK-1248, GWN-323, and those described in WO2017096179, WO2017096276, WO2017096189, and WO2018089628. In some embodiments, antibodies or fragments thereof that co-target TNFRSF4 (OX40) and TNFRSF18 (GITR) are co-administered. Such antibody systems are described, for example, in WO2017096179 and WO2018089628. Bispecific antibodies targeting members of the TNFRSF family that can be co-administered include PRS-343 (CD-137 / HER2), AFM26 (BCMA / CD16A), AFM-13 (CD16 / CD30), ozogonisab (REGN-1979; CD20 / CD3), AMG-420 (BCMA / CD3), INHIBRX-105 (4-1BB / PDL1), FAP-4-IBBL (4-1BB / FAP), plamotamab (XmAb-13676; CD3 / CD20), RG-7828 (CD20 / CD3), CC-93269 (CD3 / BCMA), REGN-5458 (CD3 / BCMA), and IMM-0306 (CD47 / CD20). TGFb antagonists In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, are administered together with a TGFβ antagonist. In some embodiments, the TGFβ antagonist is a TGFβ-specific antibody. TGFβ-specific antibodies can be prepared and characterized using methods known to those skilled in the art, such as those described in PCT International Application Publication No. WO 2018 / 129329 and U.S. Patent No. 9,518,112. In some embodiments, the TGFβ antagonist binds to a latent TGFβ-related peptide (LAP), such as TGFβ1-LAP. TGFβ1 LAP-specific antibodies can be prepared and characterized using methods known to those skilled in the art, such as those described in U.S. Patent Nos. 8,198,412 or 10,017,567. In some embodiments, the TGFβ antagonist binds to TGFβ (e.g., TGFβ1) in a kinase-independent manner (e.g., independent of the presence of TGFβ in a particular tissue or organ). In some embodiments, the TGFβ antagonist binds to TGFβ (e.g., TGFβ1) in a kinase-dependent manner. In some embodiments, the TGFβ antagonist blocks the activation of latent TGFβ (e.g., latent TGFβ1) located in the extracellular matrix, such as in the connective tissue of the liver. In some embodiments, a TGFβ antagonist blocks the activation of latent TGFβ (e.g., latent TGFβ 1) located in the thymus, lymph nodes, or tumor microenvironment (e.g., in patients with liver cancer). In some embodiments, a TGFβ antagonist blocks the activation of latent TGFβ (e.g., latent TGFβ 1) by means of latent TGFβ-binding protein (LTBP). In some embodiments, a TGFβ antagonist blocks the activation of latent TGFβ (e.g., latent TGFβ 1) by means of, for example, glycoprotein-A repeat principal protein (GARP) described in U.S. Patent No. 10,000,572. In some embodiments, a TGFβ antagonist is ARGX-115. In some embodiments, a TGFβ antagonist is SK-181. In some embodiments, a TGFβ antagonist is an anti-latent-related peptide (LAP) antibody that specifically binds to the LAP-TGFβ complex.In some embodiments, an anti-LAP antibody specifically binds to the LAP-TGFβ complex in the extracellular matrix (ECM), such as in the connective tissue of the liver. In some embodiments, an anti-LAP antibody specifically binds to the LAP-TGFβ complex on the surface of certain immunosuppressive cell types, such as regulatory T cells (Tregs), tumor-associated macrophages, or myeloid-derived suppressor cells, in the tumor microenvironment. In some embodiments, an anti-LAP anti-system TLS-01 antibody is used. In some embodiments, an anti-LAP antibody specifically binds to the LAP-TGFβ complex in any choroid. In some embodiments, an anti-LAP anti-system TLS-02 antibody is used. In some embodiments, a TGFβ antagonist comprises a TGFβ receptor. In some embodiments, a TGFβ antagonist is a TGFβ receptor-Fc fusion protein. In some embodiments, a TGFβ antagonist is an antibody comprising a TGFβ receptor. TGFβ antagonists containing TGFβ receptors that can be used in the compositions and methods provided herein have been described, for example, in PCT International Publications WO 2019 / 113123 A1 and WO 2019 / 113464 A1. Bispecific. T-cell connective In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or their pharmaceutically acceptable salt series, are administered together with a bispecific T-cell connector (e.g., without Fc) or an anti-CD3 bispecific antibody (e.g., with Fc). Examples of co-administerable anti-CD3 bispecific antibodies or BiTEs include duvortuxizumab (JNJ-64052781; CD19 / CD3), AMG-211 (CEA / CD3), AMG-160 (PSMA / CD3), RG7802 (CEA / CD3), ERY-974 (CD3 / GPC3), PF-06671008 (cadherin / CD3), APVO436 (CD123 / CD3), flotetuzumab (CD123 / CD3), and ozonizumab (REGN-1979;CD20 / CD3), MCLA-117 (CD3 / CLEC12A), JNJ-0819 (blood matrix / CD3), JNJ-7564 (CD3 / blood matrix), AMG-757 (DLL3-CD3), AMG-330 (CD33 / CD3), AMG-420 (BCMA / CD3), AMG-427 (FLT3 / CD3), AMG-562 (CD19 / CD3), AMG-596 (EGFRvIII / CD3), AMG-673 (CD33 / CD3), AMG-701 (BCMA / CD3), AMG-757 (DLL3 / CD3), AMG-211 (CEA / CD3), blinatumomab (CD19 / CD3), huGD2-BsAb (CD3 / GD2), ERY974 (GPC3 / CD3), GEMoab (CD3 / PSCA), RG6026 (CD20 / CD3), RG6194 (HER2 / CD3), PF-06863135 (BCMA / CD3), SAR440234 (CD3 / CDw123), JNJ-9383 (MGD-015), AMG-424 (CD38 / CD3), tidutamab (XmAb-18087 (SSTR2 / CD3)), JNJ-63709178 (CD123 / CD3), MGD-007 (CD3 / gpA33), MGD-009 (CD3 / B7H3), IMCgp100 (CD3 / gp100), XmAb-14045 (CD123 / CD3), XmAb-13676 (CD3 / CD20), tidutamab (XmAb-18087; SSTR2 / CD3), catumaxomab (CD3 / EpCAM), REGN-4018 (MUC16 / CD3), mosunetuzumab (RG-7828);CD20 / CD3), CC-93269 (CD3 / BCMA), REGN-5458 (CD3 / BCMA), GRB-1302 (CD3 / Erbb2), GRB-1342 (CD38 / CD3), GEM-333 (CD3 / CD33). Depending on the application, anti-CD3 binding bispecific molecules may or may not have an Fc. Descriptive bispecific T-cell connectives that can be co-administered target CD3 and tumor-associated antigens as described herein, including, for example, CD19 (e.g., lantomoxicillin); CD33 (e.g., AMG330); CEA (e.g., MEDI-565); receptor tyrosine kinase-like orphan receptor 1 (ROR1) (Gohil, ; et al., Oncoimmunology.(2017) May 17; 6(7):e1326437); PD-L1 (Horn, et al., Oncotarget.2017 Aug 3; 8(35):57964-57980); and EGFRvIII (Yang, et al., Cancer Lett. 2017 Sep 10; 403:224-230). Bispecific and trispecific natural killers. (NK) cell connective In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are used in conjunction with bispecific NK cell connectives (BiKE) or trispecific NK cells. Interchangeors (TriKEs) (e.g., without Fc) or bispecific antibodies (e.g., with Fc) can be co-administered with: NK cell activation receptors (e.g., CD16A), C-type lectin receptors (CD94 / NKG2C, NKG2D, NKG2E / H, and NKG2F), native cytotoxic receptors (NKp30, NKp44, and NKp46), killer cell C-type lectin-like receptors (NKp65, NKp80), Fc receptor FcγR (which mediates antibody-dependent cytotoxicity), SLAM family receptors (e.g., 2B4, SLAM6, and SLAM7), killer cell immunoglobulin-like receptors (KIRs) (KIR-2DS and KIR-3DS), DNAM-1, and CD137 (41BB). Illustrated anti-CD16 bispecific antibodies, BiKEs, or TriKEs that can be co-administered include AFM26 (BCMA / CD16A) and AFM-13 (CD16 / CD30). Depending on the context, anti-CD16 binding bispecific molecules may or may not have an Fc. Descriptive bispecific NK cell connectors that can be co-administered target CD16 and one or more tumor-associated antigens as described herein, including, for example, CD19, CD20, CD22, CD30, CD33, CD123, EGFR, EpCAM, ganglioside GD2, HER2 / neu, HLA type II, and FOLR1. BiKE and TriKE are described in, for example, Felices, et al., Methods Mol Biol. (2016) 1441:333–346; Fang, et al., Semin Immunol. (2017) 31:37-54. MCL1 apoptosis regulator ( (BCL2 family members) (MCL1) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with inhibitors of: MCL1 apoptosis regulators, BCL2 family members (MCL1,TM; EAT; MCL1L; MCL1S; Mcl-1; BCL2L3; MCL1-ES; bcl2-L-3; mcl1 / EAT; NCBI gene ID: 4170). Examples of MCL1 inhibitors include tapotoclax (AMG-176), AMG-397, S-64315, AZD-5991, 483-LM, A-1210477, UMI-77, JKY-5-037, PRT-1419, GS-9716, and those described in WO2018183418, WO2016033486, and WO2017147410. SHP2 inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with an inhibitor of protein tyrosine phosphatase non-receptor type 11 (PTPN11; BPTP3, CFC, JMML, METCDS, NS1, PTP-1D, PTP2C, SH-PTP2, SH-PTP3, SHP2; NCBI gene ID: 5781). Examples of SHP2 inhibitors include TNO155 (SHP-099), RMC-4550, JAB-3068, RMC-4630, and those described in WO2018172984 and WO2017211303. Hematopoietic progenitor cell kinases 1 (HPK1) Inhibitors and Degrading Agents In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with an inhibitor of cleavage-inducing protein kinase kinase 1 (MAP4K1, HPK1; NCBI gene ID: 11184). Examples of hematopoietic progenitor cell kinase 1 (HPK1) inhibitors include, but are not limited to, those described in WO2020092621, WO2018183956, WO2018183964, WO2018167147, WO2018049152, WO2020092528, WO2016205942, WO2016090300, WO2018049214, WO2018049200, WO2018049191, WO2018102366, WO2018049152, and WO2016090300. Apoptosis signal-regulated kinases (ASK) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, are administered together with an ASK inhibitor, such as cleavage-inducing protein kinase kinase 5 (MAP3K5; ASK1, MAPKKK5, MEKK5; NCBI gene ID: 4217). Examples of ASK1 inhibitors include those described in WO2011008709 (Gilead Sciences) and WO 2013112741 (Gilead Sciences). Bruton's tyrosine kinase (BTK) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with an inhibitor of Bruton's tyrosine kinases (BTK, AGMX1, AT, ATK, BPK, IGHD3, IMD1, PSCTK1, XLA; NCBI gene ID: 695). Examples of BTK inhibitors include (S)-6-amino-9-(1-(but-2-ynyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one, acalabrutinib (ACP-196), zanubrutinib (BGB-3111), CB988, HM71224, ibrutinib, M-2951 (evobrutinib), M7583, tirabrutinib (ONO-4059), PRN-1008, and spebrutinib. (CC-292), TAK-020, vecabrutinib, ARQ-531, SHR-1459, DTRMWXHS-12, PCI-32765, and TAS-5315. Cyclin-dependent kinases. (CDK) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with inhibitors of: cyclin-dependent kinase 1 (CDK1, CDC2; CDC28A; P34CDC2; NCBI gene ID: 983); cyclin-dependent kinase 2 (CDK2, CDKN2; p33(CDK2); NCBI gene ID: 1017); cyclin-dependent kinase 3 (CDK3; NCBI gene ID: 1018); cyclin-dependent kinase 4 (CDK4, CMM3; PSK-J3; NCBI gene ID: 1019); cyclin-dependent kinase 6 (CDK6, MCPH12; PLSTIRE; NCBI gene ID: 1021); cyclin-dependent kinase 7 (CDK7, CAK; CAK1; HCAK; MO15; STK1; CDKN7; p39MO15; NCBI gene ID: 1022), or cyclin-dependent kinase 9 (CDK9, TAK; C-2k; CTK1; CDC2L4; PITALRE; NCBI gene ID: 1025). Inhibitors of CDK 1, 2, 3, 4, 6, 7, and / or 9 include abemaciclib, avocidib (HMR-1275, flavopiridol), AT-7519, dinacilib, ibrance, FLX-925, LEE001, palbociclib, samuraciclib, ribociclib, rigosertib, selinexor, UCN-01, SY1365, CT-7001, SY-1365, G1T38, milciclib, trilaciclib, simurosertib hydrate (TAK931), and TG-02. Disk-based protein domain receptors (DDR) inhibitors In some embodiments, the formulas provided herein are (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI) (VIa) or its pharmaceutically acceptable salts in combination with inhibitors of the following: disk-based receptor tyrosine kinase 1 (DDR1, CAK, CD167, DDR, EDDR1, HGK2, MCK10, NEP, NTRK4, PTK3, PTK3A, RTK6, TRKE; NCBI gene ID: 780); and / or disk-based receptor tyrosine kinase 2 (DDR2, MIG20a, NTRKR3, TKT, TYRO10, WRCN; NCBI gene ID: 4921). Examples of DDR inhibitors include dasatinib and those disclosed in WO2014 / 047624 (Gilead Sciences), US 2009-0142345 (Takeda Pharmaceutical), US 2011-0287011 (Oncomed Pharmaceuticals), WO 2013 / 027802 (Chugai Pharmaceutical), and WO2013 / 034933 (Imperial Innovations). Targeted E3 conjugase ligand conjugate In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or their pharmaceutically acceptable salts, are administered together with E3 conjugate ligand conjugates. Such conjugates have a target protein binding moiety and an E3 conjugase binding moiety (e.g., an E3 ubiquitin conjugase binding moiety for apoptosis protein inhibitors (IAPs) such as XIAP, c-IAP1, c-IAP2, NIL-IAP, Bruce, and Survival, a Von Hippel-Lindau E3 ubiquitin conjugase (VHL) binding moiety, a Selenbrom E3 ubiquitin conjugase binding moiety, and a mouse dual microsome 2 homolog (MDM2) E3 ubiquitin conjugase binding moiety), and can be used, for example, via the ubiquitin pathway to promote or increase the degradation of the target protein. In some embodiments, the E3 conjugase ligand conjugate comprises a targeting or binding moiety that targets or binds the protein described herein and an E3 conjugase ligand or binding moiety. In some embodiments, the E3 conjugase ligand conjugate comprises a targeting or binding portion that targets or binds to a protein selected from: Cbl proto-oncogene B (CBLB; Cbl-b, Nbla00127, RNF56; NCBI gene ID: 868) and hypoxia-inducible factor 1st subunit α (HIF1A; NCBI gene ID: 3091). In some embodiments, the E3 conjugase ligand conjugate comprises a kinase inhibitor (e.g., a small molecule kinase inhibitor of BTK and an E3 conjugase ligand or binding portion). See, for example, WO2018098280. In some embodiments, the E3 conjugase ligand conjugate comprises a binding portion that targets or binds to interleukin-1 (IL-1) receptor-associated kinase 4 (IRAK-4); rapidly accelerating fibrosarcoma (RAF, such as c-RAF, A-RAF, and / or B-RAF), c-Met / p38, or BRD protein; and an E3 conjugase ligand or binding portion. See examples such as WO2019099926, WO2018226542, WO2018119448, WO2018223909, and WO2019079701.Additional co-administerable targeting E3 conjugase ligand conjugates are described, for example, in WO2018237026, WO2019084026, WO2019084030, WO2019067733, WO2019043217, WO2019043208, and WO2018144649. Histone deacetase. (HDAC) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with an inhibitor of histone deacetase, such as histone deacetase 9 (HDAC9, HD7, HD7b, HD9, HDAC, HDAC7, HDAC7B, HDAC9B, HDAC9FL, HDRP, MITR; gene ID: 9734). Examples of HDAC inhibitors include abexistat, ACY-241, AR-42, BEBT-908, belinstat, CKD-581, CS-055 (HBI-8000), CUDC-907 (fenmicstat), entenostat, givenolactone, mosenostat, pabistat, pranostat, quinsinostat (JNJ-26481585), reminolactone, riconolactone, SHP-141, valproic acid (VAL-001), vorinostat, tenostin, remist, and entenostat. Indoleamine -pyrrole -2,3-dioxygenase (IDO1) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1; NCBI gene ID: 3620). Examples of IDO1 inhibitors include BLV-0801, epacadostat, linrodostat (F-001287, BMS-986205), GBV-1012, GBV-1028, GDC-0919, indoximod, NKTR-218, NLG-919-based vaccines, PF-06840003, piperanaquinone derivatives (SN-35837), resminostat, SBLK-200802, shIDO-ST, EOS-200271, KHK-2455, and LY-3381916. Janus kinase (JAK) inhibitors In some embodiments, the formulas provided herein are (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va). The compound of (VI), or (VIa), or its pharmaceutically acceptable salts, may be administered together with inhibitors of the following: Janus kinase 1 (JAK1, JAK1A, JAK1B, JTK3; NCBI gene ID: 3716); Janus kinase 2 (JAK2, JTK10, THCYT3; NCBI gene ID: 3717); and / or Janus kinase 3 (JAK3, JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK; NCBI gene ID: 3718). Examples of JAK inhibitors include AT9283, AZD1480, baricitinib, BMS-911543, fedratinib, figotinib (GLPG0634), gandotinib (LY2784544), INCB039110 (itacitinib), lestaurtinib, morolotinib (CYT0387), ilginatinib maleate (NS-018), pacritinib (SB1518), peficitinib (ASP015K), ruxolitinib, tofacitinib (formerly tasocitinib), INCB052793, and XL019. lysine oxidase-like protein (LOXL) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with inhibitors of: LOXL proteins, such as LOXL1 (NCBI gene ID: 4016), LOXL2 (NCBI gene ID: 4017), LOXL3 (NCBI gene ID: 84695), LOXL4 (NCBI gene ID: 84171), and / or LOX (NCBI gene ID: 4015). Examples of LOXL2 inhibitors include antibodies described in WO 2009017833 (Arresto Biosciences), WO 2009035791 (Arresto Biosciences), and WO 2011097513 (Gilead Biologics). Matrix metalloproteinases (MMP) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or their pharmaceutically acceptable salts, are administered together with inhibitors of matrix metallopeptidases (MMPs), such as inhibitors of the following: MMP1 (NCBI gene ID: 4312), MMP2 (NCBI gene ID: 4313), MMP3 (NCBI gene ID: 4314), MMP7 (NCBI gene ID: 4316), MMP8 (NCBI gene ID: 4317), MMP9 (NCBI gene ID: 4318), MMP9 (NCBI gene ID: 4319), ... MMP10 (NCBI gene ID: 4318); MMP11 (NCBI gene ID: 4320); MMP12 (NCBI gene ID: 4321), MMP13 (NCBI gene ID: 4322), MMP14 (NCBI gene ID: 4323), MMP15 (NCBI gene ID: 4324), MMP16 (NCBI gene ID: 4325), MMP17 (NCBI gene ID: 4326) MMP19 (NCBI gene ID: 4327), MMP20 (NCBI gene ID: 9313), MMP21 (NCBI gene ID: 118856), MMP24 (NCBI gene ID: 10893), MMP25 (NCBI gene ID: 64386), MMP26 (NCBI gene ID: 56547), MMP27 (NCBI gene ID: 64066), and / or MMP28 (NCBI gene ID: 79148). Examples of MMP9 inhibitors include marimastat (BB-2516), cipemastat (Ro 32-3555), GS-5745 (andecaliximab), and those described in WO 2012027721 (Gilead Biologics). RAS and RAS pathway inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with inhibitors of: the KRAS proto-oncogene, GTPase (KRAS; also known as NS; NS3; CFC2; RALD; K-Ras; KRAS1; KRAS2; RASK2; KI-RAS; CK-RAS; K-RAS2A; K-RAS2B; K-RAS4A; K-RAS4B; c-Ki-ras2; NCBI gene ID: 3845); NRAS proto-oncogene (GTPase) (NRAS; also known as NS6; CMNS; NCMS; ALPS4; N-ras; NRAS1; NCBI gene ID: 4893) or HRAS proto-oncogene, GTPase (HRAS; also known as CTLO; KRAS; HAMSV; HRAS1; KRAS2; RASH1; RASK2; Ki-Ras; p21ras; CH-RAS; cK-ras; H-RASIDX; c-Ki-ras; C-BAS / HAS; C-HA-RAS1; NCBI gene ID: 3265). Ras inhibitors can inhibit Ras at the polynucleotide (e.g., transcription inhibitors) or peptide (e.g., GTPase inhibitors) level. In some embodiments, the inhibitor targets one or more proteins in the Ras pathway, such as inhibiting one or more of EGFR, Ras, Raf (A-Raf, B-Raf, C-Raf), MEK (MEK1, MEK2), ERK, PI3K, AKT, and mTOR.Exemplary co-administerable K-Ras inhibitors include sotorasib (AMG-510), COTI-219, ARS-3248, WDB-178, BI-3406, BI-1701963, SML-8-73-1 (G12C), adagrasib (MRTX-849), ARS-1620 (G12C), SML-8-73-1 (G12C), compound 3144 (G12D), Kobe0065 / 2602 (Ras GTP), RT11, MRTX-849 (G12C), and selective K-Ras (G12D) inhibitory peptides, including KRpep-2 and KRpep-2d. Examples. KRAS mRNA inhibitors include anti-KRAS U1 transferin, AZD-4785, siG12D-LODER™, and siG12D extracellular matrix. Examples of co-administerable MEK inhibitors include binitinib, cobitinib, PD-0325901, pemate, RG-7304, selumetinib, trametinib, and those described below and herein. Examples of co-administerable Raf dimer inhibitors include BGB-283, HM-95573, LXH-254, LY-3009120, RG7304, and TAK-580. Examples of co-administerable ERK inhibitors include LTT-462, LY-3214996, MK-8353, ravoxertinib, and ulixertinib. Examples of co-administerable Ras GTPase inhibitors include regoratiib. Examples of co-administerable PI3K inhibitors include idelalisib (Zydelig®), alpelisib, buparlisib, pictilisib, inavicib (RG6114), and ASN-003. Examples of co-administerable AKT inhibitors include calvatiib and GSK2141795. Examples of co-administerable PI3K / mTOR inhibitors include dactolisib, omipalisib, voxtalisib, gedatolisib, GSK2141795, GSK-2126458, invoxib (RG6114), sapanisertib, ME-344, sirolimus (oral nanocrystalline formulation, for cancer), racemetyrosine (TYME-88 (mTOR / cytochrome P450 3A4)), temsirolimus (TORISEL®, CCI-779), CC-115, onatasertib (CC-223), SF-1126, and PQR-309 (bimiralisib). In some embodiments, Ras-driven cancers with CDKN2A mutations (e.g., NSCLC) can be suppressed by co-administration of the MEK inhibitor selumetinib and the CDK4 / 6 inhibitor palbociclib. See, for example, Zhou, et al., Cancer Lett. 2017 Nov 1; 408:130-137. Furthermore, K-RAS and mutant N-RAS can be reduced by the irreversible ERBB1 / 2 / 4 inhibitor neratinib. See, for example, Booth, et al., Cancer Biol Ther. 2018 Feb 1; 19(2):132-137. Cleavage-inducing substances activate protein kinases. (MEK) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with an inhibitor of: cleavage-inducing protein kinase kinase kinase 7 (MAP2K7, JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7, SAPKK-4, SAPKK4; NCBI gene ID: 5609). Examples of MEK inhibitors include anquinolone, binitinib, cobimetinib (GDC-0973, XL-518), MT-144, selumetinib (AZD6244), sorafenib, trametinib (GSK1120212), alprazostig + trametinib, PD-0325901, pemateti, LTT462, AS703988, CC-90003, and refatinib. Phosphatidylinositol 3-kinase (PI3K) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with an inhibitor of: phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunits, such as phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunit α (PIK3CA, C LAPO, CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, PI3K-α, p110-α; NCBI gene ID: 5290); phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit β (PIK3CB, P110BETA, PI3K, PI3KBETA, PIK3C1; NCBI gene ID: 5291); phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG, PI3CG, PI3K, PI3Kγ, PIK3, p110γ, p120-PI3K; gene ID: 5494); and / or phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit δ (PIK3CD, APDS, IMD14, P110δ, PI3K, p110D; NCBI gene ID: 5293). In some embodiments, the PI3K inhibitor is a pan-PI3K inhibitor.Examples of PI3K inhibitors include ACP-319, AEZA-129, AMG-319, AS252424, AZD8186, BAY 10824391, BEZ235, bupazoxib (BKM120), BYL719 (ipexicoxib), CH5132799, copanlisib (BAY 80-6946), duvelisib, GDC-0032, GDC-0077, GDC-0941, GDC-0980, GSK2636771, GSK2269557, edoxib (Zydelig®), INCB50465, IPI-145, IPI-443, IPI-549, KAR4141, LY294002, and LY3. 023414, MLN1117, OXY111A, PA799, PX-866, RG7604, Regoracitabine, RP5090, RP6530, SRX3177, Taselisib, TG100115, TGR-1202 (Umbrasib), TGX221, WX-037, X-339, X-414, XL147 (SAR245408), XL499, XL756, wortmannin, ZSTK474, and compounds described in WO2005113556 (ICOS), WO 2013 / 052699 (Gilead Calistoga), WO2013116562 (Gilead Calistoga), WO2014100765 (Gilead Calistoga), WO2014100767 (Gilead Calistoga), and WO2014201409 (Gilead Sciences). Splenic tyrosine kinase. (SYK) inhibitors In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salts thereof, provided herein, are administered together with an inhibitor of spleen-associated tyrosine kinase (SYK, p72-Syk, NCBI gene ID: 6850). Examples of SYK inhibitors include 6-(1H-indazole-6-yl)-N-(4-N-yl)- (Linylphenyl)imidazo[1,2-a]pyridine -8-amine, BAY-61-3606, cerdulatinib (PRT-062607), entotinib, fostamatinib (R788), HMPL-523, NVP-QAB 205 AA, R112, R343, tamatinib (R406), gousatinib (ASN-002), and those described in US8450321 (Gilead Connecticut) and US20150175616. Tridonic receptor. (TLR) agonist In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or pharmaceutically acceptable salt-based and thallium-like receptors (TL receptors) provided herein, are included. Administer agonists together with TLR1 (NCBI gene ID: 7096), TLR2 (NCBI gene ID: 7097), TLR3 (NCBI gene ID: 7098), TLR4 (NCBI gene ID: 7099), TLR5 (NCBI gene ID: 7100), TLR6 (NCBI gene ID: 10333), TLR7 (NCBI gene ID: 51284), TLR8 (NCBI gene ID: 51311), TLR9 (NCBI gene ID: 54106), and / or TLR10 (NCBI gene ID: 81793).Examples of co-administerable TLR7 agonists include DS-0509, GS-9620 (vesatolimod), vesatolimod analogs, LHC-165, TMX-101 (imiquimod), GSK-2245035, resiquimod, DSR-6434, DSP-3025, IMO-4200, MCT-465, MEDI-9197, 3M-051, SB-9922, 3M-052, Limtop, TMX-30X, TMX-202, RG-7863, RG-7795, BDB-001, DSP-0509, and the compounds disclosed below: US20100143301 (Gilead Sciences), US20110098248 (Gilead Sciences). Sciences), and US20090047249 (Gilead Sciences), US20140045849 (Janssen), US20140073642 (Janssen), WO2014056953 (Janssen), WO2014076221 (Janssen), WO2014128189 (Janssen), US20140350031 (Janssen), WO2014023813 (Janssen), US20080234251 (Array Biopharma), US20080306050 (Array Biopharma), US20100029585 (Ventirx Pharma), US20110092485 (Ventirx Pharma), US20110118235 (Ventirx Pharma), US20120082658 (Ventirx Pharma), US20120219615 (Ventirx Pharma), US20140066432 (Ventirx Pharma), US20140088085 (Ventirx Pharma), US20140275167 (Novira Therapeutics), and US20130251673 (Novira Therapeutics). The co-administerable TLR7 / TLR8 agonist is NKTR-262.Examples of co-administerable TLR8 agonists include E-6887, IMO-4200, IMO-8400, IMO-9200, MCT-465, MEDI-9197, motolimod, ricilimod, GS-9688, VTX-1463, VTX-763, 3M-051, 3M-052, and the compounds disclosed below: US20140045849 (Janssen), US20140073642 (Janssen), WO2014 / 056953 (Janssen), WO2014 / 076221 (Janssen), WO2014 / 128189 (Janssen), US20140350031 (Janssen), WO2014 / 023813 (Janssen), US20080234251 (Array Biopharma), US20080306050 (Array Biopharma), US20100029585 (Ventirx Pharma), US20110092485 (Ventirx Pharma), US20110118235 (Ventirx Pharma), US20120082658 (Ventirx Pharma), US20120219615 (Ventirx Pharma), US20140066432 (Ventirx Pharma), US20140088085 (Ventirx Pharma), US20140275167 (Novira Therapeutics), and US20130251673 (Novira Therapeutics). Examples of co-administerable TLR9 agonists include AST-008, CMP-001, IMO-2055, IMO-2125, litenimod, MGN-1601, BB-001, BB-006, IMO-3100, IMO-8400, IR-103, IMO-9200, agatolimod, DIMS-9054, DV-1079, DV-1179, AZD-1419, leftolimod (MGN-1703), CYT-003, CYT-003-QbG10, and PUL-042. Examples of TLR3 agonists include rintatolimod, poly-ICLC, RIBOXXON®, Apoxxim, RIBOXXIM®, IPH-33, MCT-465, MCT-475, and ND-1.1.Tyrosine kinase inhibitors. (TKI) In some embodiments, compounds of formulas (I), (Ia), (Ib), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IIg), (IIh), (IIi), (IIj), (IIk), (IIIa), (IIIa-1), (IIIa-2), (IIIa-3), (IIIb), (IIIc), (IIId), (IIIe), (IIIf), (IVa), (IVa-1), (IVa-2), (V), (Va), (VI), or (VIa), or their pharmaceutically acceptable salt derivatives, are administered together with a tyrosine kinase inhibitor (TKI). The TKI targets receptors for epidermal growth factor (EGFR), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Examples of TKIs include, but are not limited to, afatinib, ARQ-087 (derazantinib), asp5878, AZD3759, AZD4547, bosutinib, brigatinib, cabozantinib, sildenafil, crenolanib, dacomitinib, dasatinib, dovirtinib, E-6201, erdafitinib, erlotinib, gefitinib, giglitinib (ASP-2215), FP-1039, HM61713, icotinib, imatinib, and KX2-391. (Src), lapatinib, letatinib, lenvatinib, midotutolin, nintedanib, ODM-203, osimertinib (AZD-9291), ponatinib, poziotinib, quinzatinib, ratotinib, rociletinib, sulfatinib (HMPL-012), sunitinib, famitinib L-malate, (MAC-4), tivoanib, TH-4000, and MEDI-575 (anti-PDGFR antibody).Exemplary EGFR-targeting agents include neratinib, tucatinib (ONT-380), vantinib, mopotinib (TAK-788), DZD-9008, varitinib, beflutinib (ACEA-0010), EGF816 (nazatinib), olmutinib (BI-1482694), osimertinib (AZD-9291), AMG-596 (EGFRvIII / CD3), lifirafenib (BGB-283), vectibix, lazertinib (LECLAZA®), and compounds disclosed in Booth, et al., Cancer Biol Ther. 2018 Feb 1; 19(2):132-137. Antibodies targeting EGFR include, but are not limited to, modotuximab, cetuximab sarotalocan (RM-1929), seribantumab, nexituzumab, depatuxizumab mafodotin (ABT-414), tomuzotuximab, depatuxizumab (ABT-...

Claims

1. A compound of formula (I): (I) or a pharmaceutically acceptable salt thereof, wherein R 1 System-H; R 2 -H, -F, or -Cl; R 21 -H, -F, or -Cl; R 3 -H, -F, or -Cl; R 4a and R 4b Each can be independently of -H, halogen, -OH, or C. 1-6 Alkyl; Cyclic A-series C 3-10 Cycloalkyl or heterocyclic groups; n-series 0, 1, 2, 3, or 4; each R 5 Independent halogens, =O, =CH2, -CN, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-6 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, -O-(R) 51 ), or -N(R 51 (R) 52 ); where R 5 Each of the following groups can be CH2, alkyl, alkenyl, cycloalkyl, alkoxy, haloalkyl, haloalkoxy, heterocyclic, aryl, or heteroaryl, optionally with one to four identical or different R groups. 5a Replace; Each R 5a Independent halogens, -CN, C 1-6 Alkyl, C 6-10 Aryl, or -O(R) 51 ); where each R can be the same or different 51 and R 52 Independent phylogenetic system - H, C 1-6 Alkyl, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl; R 6 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 1a (R) 1b ), -S(O)(NR 1a (R) 1b -C(O)R 1c -S(O 2)R 1c 、or -C(O)OR 1d , where R 6 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 2a (R) 2b ), -S(O)(NR 2a (R) 2b -C(O)R 2c S(O 2)R 2c 、or -C(O)OR 2d , where R 7 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 20 heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, =O, imine, -NO2, -N3, -CN, -OR 3a -C(O)-R 3a -C(O)OR 3a -C(O)-N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + -N(R) 3a )C(O)-R 3b -N(R) 3a )C(O)OR 3b -N(R) 3a )C(O)N(R 3b (R) 3c ), -N(R 3a )S(O) 2(R 3b -NR 3a S(O) 2N(R 3b (R) 3c -NR 3a S(O) 2O(R 3b -OC(O)R 3a -OC(O)OR 3a -OC(O)-N(R) 3a (R) 3b ), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R) 3a (R) 3b ), -S(O)(NR 3a )R 3b -S(O)(NR) 3a )N(R 3b (R) 3c -SF5, or -Si(R) 3a ) 3; where each Z 1 Z 2 、or Z 3 The alkyl, halogen, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups may each be optionally derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 halogenated, C 1-6 Alkoxy, C 1-6 halogenated alkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 Cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, =O, -NO 2, -CN, -N 3, -OR 3a -C(O)R 3a -C(O)OR 3a -C(O)N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + -N(R) 3a )-C(O)R 3b -N(R) 3a )C(O)O(R 3b ), -N(R 3a )C(O)N(R 3b (R) 3c ), -N(R 3a )S(O) 2(R 3b ), -N(R 3a )S(O) 2-N(R 3b (R) 3c ), -N(R 3a )S(O) 2O(R 3b -OC(O)R 3a -OC(O)OR 3a -OC(O)-N(R) 3a (R) 3b ), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R) 3a (R) 3b ), -S(O)(NR 3a )R 3b 、or -Si(R 3a ) 3; where Z 1a The alkyl, halogen, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups may each be optionally derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent C 1-9 Alkyl, C 1-8 halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 Cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, lateral oxygen, -OH, -CN, -NO₂, -NH₂, -N₃, -SH, -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 2-6 alkenyl), -O(C) 2-6 alkynyl group), -O(C 3-15 cycloalkyl), -O (heterocyclic), -O (C 6-10 aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 2-6 alkenyl), -NH (C 2-6 alkynyl group), -NH(C 3-15 cycloalkyl), -NH (heterocyclic), -NH (C 6-10 aryl), -NH (heteroaryl), -N (C 1-9 Alkyl) 2, -N(C) 1-8 2, -N(C) (Halogenated groups) 2-6 Alkenyl) 2, -N(C 2-6 2, -N(C) (Alkyne group) 3-15 2-Cycloalkyl groups) 2-N (heterocyclic groups) 2-N (C 6-10 Aryl) 2,-N (heteroaryl) 2,-N (C 1-9 Alkyl)(C 1-8 Halogenated groups), -N(C) 1-9 Alkyl)(C 2-6 alkenyl), -N(C) 1-9 Alkyl)(C 2-6 alkynyl group), -N(C 1-9 Alkyl)(C 3-15 cycloalkyl), -N(C) 1-9 Alkyl (heterocyclic), -N(C) 1-9 Alkyl)(C 6-10 aryl), -N(C 1-9 Alkyl)(heteroaryl), -C(O)(C 1-9 Alkyl), -C(O)(C 1-8 Halogenated groups), -C(O)(C 2-6 alkenyl), -C(O)(C 2-6 ynyl group), -C(O)(C 3-15 cycloalkyl), -C(O)(heterocyclic), -C(O)(C 6-10 aryl), -C(O)(heteroaryl), -C(O)O(C 1-9 Alkyl), -C(O)O(C 1-8 Halogenated alkyl groups), -C(O)O(C 2-6 alkenyl), -C(O)O(C 2-6 alkynyl group), -C(O)O(C 3-15 cycloalkyl), -C(O)O (heterocyclic), -C(O)O (C 6-10 Aryl), -C(O)O (heteroaryl), -C(O)NH2, -C(O)NH(C 1-9 Alkyl), -C(O)NH(C 1-8 Halogenated groups), -C(O)NH(C 2-6 alkenyl), -C(O)NH(C 2-6 ynyl group), -C(O)NH(C 3-15 cycloalkyl), -C(O)NH (heterocyclic), -C(O)NH (C 6-10 aryl), -C(O)NH (heteroaryl), -C(O)N(C 1-9 Alkyl) 2、-C(O)N(C 1-8 2, -C(O)N(C) 2-6 Alkenyl) 2, -C(O)N(C 2-6 2, -C(O)N(C) (Alkyne group) 3-15 2, -C(O)N (heterocyclic group) 2, -C(O)N (C 6-10 Aryl) 2,-C(O)N (heteroaryl) 2,-NHC(O)(C 1-9 Alkyl), -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 2-6 alkenyl), -NHC(O)(C 2-6 ynyl group), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (C 6-10 aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 alkenyl), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (C 6-10 aryl), -NHC(O)O(heteroaryl), -NHC(O)NH(C 1-9 alkyl), -NHC(O)NH(C 1-8 Halogenated groups), -NHC(O)NH(C 2-6 alkenyl), -NHC(O)NH(C 2-6 ), -NHC(O)NH(C 3-15 cycloalkyl), -NHC(O)NH (heterocyclic), -NHC(O)NH (C 6-10 aryl), -NHC(O)NH (heteroaryl), -NHS(O)(C 1-9 alkyl), -N(C) 1-9 Alkyl)(S(O)(C) 1-9 alkyl), -S(C 1-9 alkyl), -S(C 1-8 Halogenated groups), -S(C 2-6 alkenyl), -S(C 2-6 alkynyl group), -S(C 3-15 cycloalkyl), -S (heterocyclic), -S (C 6-10 aryl), -S(heteroaryl), -S(O)N(C 1-9 Alkyl) 2、-S(O)(C 1-9 Alkyl), -S(O)(C 1-8 Halogenated groups), -S(O)(C 2-6 alkenyl), -S(O)(C 2-6 ynyl group), -S(O)(C 3-15 cycloalkyl), -S(O)(heterocyclic), -S(O)(C 6-10 Aryl), -S(O) (heteroaryl), -S(O) 2(C 1-9 Alkyl), -S(O)2(C 1-8 Halogenated groups), -S(O)2(C 2-6 alkenyl), -S(O)2(C 2-6 Alkyne group), -S(O)2(C 3-15 Cycloalkyl), -S(O)2(heterocyclic), -S(O)2(C 6-10 Aryl), -S(O)2 (heteroaryl), -S(O)(NH)(C 1-9 Alkyl), -S(O) 2NH(C 1-9 Alkyl), or -S(O)2N(C 1-9 Alkyl) 2; where Z 1b The alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally have one to three carbon atoms. 1-9 Alkyl, C 1-8 Alkyl halogen, halogen, -OH, -NH₂, -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 3-15 cycloalkyl), -O (heterocyclic), -O (aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 3-15 cycloalkyl), -NH (heterocyclic), -NH (aryl), -NH (heteroaryl), -N (C 1-9 Alkyl) 2, -N(C) 3-15 2, -NHC(O)(C) (cycloalkyl) 1-8 Halogenated groups), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (aryl), -NHC(O)O (heteroaryl), -NHC(O)NH(C 1-9 Alkyl), S(O)2(C 1-9 Alkyl), -S(O)2(C 1-8 Halogenated groups), -S(O)2(C 3-15 Cycloalkyl), -S(O)2(heterocyclic), -S(O)2(aryl), -S(O)2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl), -S(O) 2NH(C 1-9 Alkyl), or -S(O)2N(C 1-9 Alkyl) 2-substituted; each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c Independent phylogenetic system - H, C 1-9 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Substitution; wherein, unless otherwise specified, the aryl groups of the compounds of formula (I) are C 6-10 Aryl; wherein, unless otherwise specified, each heteroaryl group of the compound of formula (I) is a 5- to 12-membered heteroaryl group having one to four heteroatoms of N, O, or S; wherein, unless otherwise specified, each heterocyclic group of the compound of formula (I) is a 3- to 20-membered heterocyclic group having one to four heteroatoms of N, O, or S.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 System-H; R 2 -H, -F, or -Cl; R 3 -H, -F, or -Cl; R 4a and R 4b Each can be independently of -H, halogen, -OH, or C. 1-6 Alkyl; Cyclic A-series C 3-10 Cycloalkyl or heterocyclic groups; n-series 0, 1, 2, 3, or 4; each R 5 Independent halogens, =O, -CN, C 1-6 Alkyl, C 1-6 Halogenated, C 1-6 Haloalkoxy, C 1-6 Alkoxy, C 3-6 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, -O-(R) 51 ), or -N(R 51 (R) 52 ); where R 5 Each alkyl, cycloalkyl, alkoxy, haloalkyl, haloalkoxy, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different R groups. 5a Replace; Each R 5a Independent halogens, -CN, C 1-6 Alkyl, C 6-10 aryl, or -O(R) 51 ); where each R can be the same or different 51 and R 52 Independent phylogenetic system - H, C 1-6 Alkyl, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl; R 6 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 1a (R) 1b ), -S(O)(NR 1a (R) 1b -C(O)R 1c -S(O 2)R 1c 、or -C(O)OR 1d , where R 6 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 Cycloalkyl, heterocyclic, aryl, heteroaryl, -C(O)N(R) 2a (R) 2b ), -S(O)(NR 2a (R) 2b -C(O)R 2c S(O 2)R 2c 、or -C(O)OR 2d , where R 7 The alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may each be optionally derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 20 heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, =O, imine, -NO2, -N3, -CN, -OR 3a -C(O)-R 3a -C(O)OR 3a -C(O)-N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + -N(R) 3a )C(O)-R 3b -N(R) 3a )C(O)OR 3b -N(R) 3a )C(O)N(R 3b (R) 3c ), -N(R 3a )S(O) 2(R 3b -NR 3a S(O) 2N(R 3b (R) 3c -NR 3a S(O) 2O(R 3b -OC(O)R 3a -OC(O)OR 3a -OC(O)-N(R) 3a (R) 3b ), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R) 3a (R) 3b ), -S(O)(NR 3a )R 3b -S(O)(NR) 3a )N(R 3b (R) 3c -SF5, or -Si(R) 3a ) 3; where each Z 1 Z 2 、or Z 3 The alkyl, halogen, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups may each be optionally derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 halogenated, C 1-6 Alkoxy, C 1-6 halogenated alkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 Cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, =O, -NO 2, -CN, -N 3, -OR 3a -C(O)R 3a -C(O)OR 3a -C(O)N(R) 3a (R) 3b ), -N(R 3a (R) 3b ), -N(R 3a ) 2(R 3b ) + -N(R) 3a )-C(O)R 3b -N(R) 3a )C(O)O(R 3b ), -N(R 3a )C(O)N(R 3b (R) 3c ), -N(R 3a )S(O) 2(R 3b ), -N(R 3a )S(O) 2-N(R 3b (R) 3c ), -N(R 3a )S(O) 2O(R 3b -OC(O)R 3a -OC(O)OR 3a -OC(O)-N(R) 3a (R) 3b ), -SR 3a -S(O)R 3a -S(O)(NH)R 3a -S(O) 2R 3a -S(O) 2N(R) 3a (R) 3b ), -S(O)(NR 3a )R 3b 、or -Si(R 3a ) 3; where Z 1a The alkyl, halogen, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups may each be optionally derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent C 1-9 Alkyl, C 1-8 halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 Cycloalkyl, heterocyclic, C 6-10 Aryl, heteroaryl, phenoxy, -OH, -CN, -NO₂, -NH₂, -N₃, -SH, -O(C) 1-9 alkyl), -O(C) 1-8 halogenated), -O(C) 2-6 alkenyl), -O(C) 2-6 alkynyl group), -O(C 3-15 cycloalkyl), -O (heterocyclic), -O (C 6-10 aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 2-6 alkenyl), -NH (C 2-6 alkynyl group), -NH(C 3-15 cycloalkyl), -NH (heterocyclic), -NH (C 6-10 aryl), -NH (heteroaryl), -N (C 1-9 Alkyl) 2, -N(C) 1-8 2, -N(C) (Halogenated groups) 2-6 Alkenyl) 2, -N(C 2-6 2, -N(C) (Alkyne group) 3-15 2-Cycloalkyl groups) 2-N (heterocyclic groups) 2-N (C 6-10 Aryl) 2,-N (heteroaryl) 2,-N (C 1-9 Alkyl)(C 1-8 Halogenated groups), -N(C) 1-9 Alkyl)(C 2-6 alkenyl), -N(C) 1-9 Alkyl)(C 2-6 alkynyl group), -N(C 1-9 Alkyl)(C 3-15 cycloalkyl), -N(C) 1-9 Alkyl (heterocyclic), -N(C) 1-9 Alkyl)(C 6-10 aryl), -N(C 1-9 Alkyl)(heteroaryl), -C(O)(C 1-9 Alkyl), -C(O)(C 1-8 Halogenated groups), -C(O)(C 2-6 alkenyl), -C(O)(C 2-6 ynyl group), -C(O)(C 3-15 cycloalkyl), -C(O)(heterocyclic), -C(O)(C 6-10 aryl), -C(O)(heteroaryl), -C(O)O(C 1-9 Alkyl), -C(O)O(C 1-8 Halogenated alkyl groups), -C(O)O(C 2-6 alkenyl), -C(O)O(C 2-6 alkynyl group), -C(O)O(C 3-15 cycloalkyl), -C(O)O (heterocyclic), -C(O)O (C 6-10 Aryl), -C(O)O (heteroaryl), -C(O)NH2, -C(O)NH(C 1-9 Alkyl), -C(O)NH(C 1-8 Halogenated groups), -C(O)NH(C 2-6 alkenyl), -C(O)NH(C 2-6 ynyl group), -C(O)NH(C 3-15 cycloalkyl), -C(O)NH (heterocyclic), -C(O)NH (C 6-10 aryl), -C(O)NH (heteroaryl), -C(O)N(C 1-9 Alkyl) 2、-C(O)N(C 1-8 2, -C(O)N(C) 2-6 Alkenyl) 2, -C(O)N(C 2-6 2, -C(O)N(C) (Alkyne group) 3-15 2, -C(O)N (heterocyclic group) 2, -C(O)N (C 6-10 Aryl) 2,-C(O)N (heteroaryl) 2,-NHC(O)(C 1-9 Alkyl), -NHC(O)(C 1-8 Halogenated groups), -NHC(O)(C 2-6 alkenyl), -NHC(O)(C 2-6 ynyl group), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (C 6-10 aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 alkenyl), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (C 6-10 aryl), -NHC(O)O(heteroaryl), -NHC(O)NH(C 1-9 alkyl), -NHC(O)NH(C 1-8 Halogenated groups), -NHC(O)NH(C 2-6 alkenyl), -NHC(O)NH(C 2-6 ), -NHC(O)NH(C 3-15 cycloalkyl), -NHC(O)NH (heterocyclic), -NHC(O)NH (C 6-10 aryl), -NHC(O)NH (heteroaryl), -NHS(O)(C 1-9 alkyl), -N(C) 1-9 Alkyl)(S(O)(C) 1-9 alkyl), -S(C 1-9 alkyl), -S(C 1-8 Halogenated groups), -S(C 2-6 alkenyl), -S(C 2-6 alkynyl group), -S(C 3-15 cycloalkyl), -S (heterocyclic), -S (C 6-10 aryl), -S(heteroaryl), -S(O)N(C 1-9 Alkyl) 2、-S(O)(C 1-9 Alkyl), -S(O)(C 1-8 Halogenated groups), -S(O)(C 2-6 alkenyl), -S(O)(C 2-6 ynyl group), -S(O)(C 3-15 cycloalkyl), -S(O)(heterocyclic), -S(O)(C 6-10 Aryl), -S(O) (heteroaryl), -S(O) 2(C 1-9 Alkyl), -S(O)2(C 1-8 Halogenated groups), -S(O)2(C 2-6 alkenyl), -S(O)2(C 2-6 Alkyne group), -S(O)2(C 3-15 Cycloalkyl), -S(O)2(heterocyclic), -S(O)2(C 6-10 Aryl), -S(O)2 (heteroaryl), -S(O)(NH)(C 1-9 Alkyl), -S(O) 2NH(C 1-9 Alkyl), or -S(O)2N(C 1-9 Alkyl) 2; where Z 1b The alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally have one to three carbon atoms. 1-9 Alkyl, C 1-8 Alkyl halogen, halogen, -OH, -NH₂, -O(C) 1-9 alkyl), -O(C) 1-8 Halogenated groups), -O(C) 3-15 cycloalkyl), -O (heterocyclic), -O (aryl), -O (heteroaryl), -NH (C 1-9 alkyl), -NH(C) 1-8 Halogenated groups), -NH(C) 3-15 cycloalkyl), -NH (heterocyclic), -NH (aryl), -NH (heteroaryl), -N (C 1-9 Alkyl) 2, -N(C) 3-15 2, -NHC(O)(C) (cycloalkyl) 1-8 Halogenated groups), -NHC(O)(C 3-15 cycloalkyl), -NHC(O) (heterocyclic), -NHC(O) (aryl), -NHC(O) (heteroaryl), -NHC(O)O(C 1-9 Alkyl), -NHC(O)O(C 1-8 Halogenated groups), -NHC(O)O(C 2-6 ynyl group), -NHC(O)O(C 3-15 cycloalkyl), -NHC(O)O (heterocyclic), -NHC(O)O (aryl), -NHC(O)O (heteroaryl), -NHC(O)NH(C 1-9 Alkyl), S(O)2(C 1-9 Alkyl), -S(O)2(C 1-8 Halogenated groups), -S(O)2(C 3-15 Cycloalkyl), -S(O)2(heterocyclic), -S(O)2(aryl), -S(O)2(heteroaryl), -S(O)(NH)(C 1-9 Alkyl), -S(O) 2NH(C 1-9 Alkyl), or -S(O)2N(C 1-9 Alkyl) 2-substituted; each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c Independent phylogenetic system - H, C 1-9 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein each R 1a R 1b R 1c R 1d R 2a R 2b R 2c R 2d R 3a R 3b and R 3c The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl groups are each optionally derived from one to four identical or different Z groups. 1b Substitution; wherein, unless otherwise specified, the aryl groups of the compounds of formula (I) are C 6-10 Aryl; wherein, unless otherwise specified, each heteroaryl group of the compound of formula (I) is a 5- to 12-membered heteroaryl group having one to four heteroatoms of N, O, or S; wherein, unless otherwise specified, each heterocyclic group of the compound of formula (I) is a 3- to 20-membered heterocyclic group having one to four heteroatoms of N, O, or S.

3. The compound of claim 1 or claim 2 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (Ia): (Ia).

4. The compound of claim 1 or 2 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (Ib): (Ib).

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 System-H; R 2 -H or -F; R 21 -H or -F; R 3 -H or -F; R 4a and R 4b Each independently belongs to the -H -F or -CH 3 group; the cyclic A group consists of cyclopentyl, cyclohexyl, cycloheptyl, cyclohexenyl, or tetrahydropiperanyl rings; the n group consists of 0, 1, or 2 rings; each R 5 Independently, it can be -F, -OH, -CH3, =CH2, -CH2-OH, or -O-CH3; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 6 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 7 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 12-membered heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, =O, -CN, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a ; among which each Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, -CN, -OR 3a , or -S(O) 2R 3a Z 1a Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -CN, where Z 1b Each alkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is unsubstituted; each R 3a Independent phylogenetic system - H, C 1-9 Alkyl, C 6-10 aryl or heteroaryl, wherein R 3a Each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one to four 5 to 12 heteroaryl groups, each independently of a heteroatom of N, O, or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one to four 3 to 20 heterocyclic groups, each independently of a heteroatom of N, O, or S.

6. A compound or a pharmaceutically acceptable salt thereof, as specified in any of claims 1 to 5, wherein R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a and R 4b Each independently belongs to the -H -F or -CH 3 group; the cyclic A group consists of cyclopentyl, cyclohexyl, cyclohexenyl, or tetrahydropiperanyl rings; the n group consists of 0, 1, or 2 rings; each R 5 Independently associated with -F, -OH, -CH3, or -O-CH3; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 6 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-8 Alkyl, C 1-6 Halogenated, C 3-12 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 7 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 12-membered heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, =O, -CN, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a ; among which each Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, -CN, -OR 3a , or -S(O) 2R 3a Z 1a Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -CN, where Z 1b Each alkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is unsubstituted; each R 3a Independent phylogenetic system - H, C 1-9 Alkyl, C 6-10 aryl or heteroaryl, wherein R 3a Each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one to four 5 to 12 heteroaryl groups, each independently of a heteroatom of N, O, or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one to four 3 to 20 heterocyclic groups, each independently of a heteroatom of N, O, or S.

7. A compound or a pharmaceutically acceptable salt thereof, as specified in any of claims 1 to 6, wherein R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a and R 4b Each independently belongs to the -H or -F group; cyclic A group: cyclohexyl, cyclohexenyl, or tetrahydropiperanyl ring; n group: 0; R 6 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 6 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 1 Replace; R 7 Series-H, C 1-6 Alkyl, C 1-6 Halogenated, C 3-10 cycloalkyl, heterocyclic, C 6-10 aryl or heteroaryl, wherein R 7 Each alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic group system comprises 3 to 12-membered heterocyclic groups, each with 0 to 3 additional heteroatoms, each independently consisting of N, O, or S; Each Z 1 Z 2 、or Z 3 Independent halogens, =O, -CN, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a ; among which each Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independent phyla - D, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkoxyalkyl, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, -CN, -OR 3a , or -S(O) 2R 3a Z 1a Each alkyl, haloalkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 2-6 alkenyl, C 2-6 Alkyne, halogen, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -CN, where Z 1b Each alkyl, alkenyl, ynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group is unsubstituted; each R 3a Independent phylogenetic system - H, C 1-9 Alkyl, C 6-10 aryl or heteroaryl, wherein R 3a Each alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one to four 5 to 12 heteroaryl groups, each independently of a heteroatom of N, O, or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one to four 3 to 20 heterocyclic groups, each independently of a heteroatom of N, O, or S.

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 System-H; R 2 -H or -F; R 21 -H or -F; R 3 -H or -F; R 4a The series is -H, -F, or -CH 3, and R 4b System-H; Ring A system, , , , , , or; n system 0, 1, or 2; Each R 5 Independently, it can be -F, -OH, -CH3, =CH2, -CH2-OH, or -O-CH3; R 6 System -H or optionally via a Z 1 Replacement C 1-6 Alkyl, wherein Z 1 It has not been replaced; R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10 aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic system has a 3- to 7-membered heterocyclic group with an additional N; each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, O, and C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-15 cycloalkyl, C 6-10 aryl, heterocyclic, heteroaryl, or -OR 3a Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl groups, halogens, -CN, or -S(O)2R 3a Z 1a Each alkyl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent halogens, C 3-15 cycloalkyl, or C 6-10 Aryl, of which Z 1b Each cycloalkyl or aryl group is unsubstituted; each R 3a Independent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one or two 5- to 6-membered heteroaryl groups, each independently of a heteroatom of N or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one or two 3- to 7-membered heterocyclic groups, each independently of a heteroatom of N or O.

9. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 8, wherein R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a The series is -H, -F, or -CH 3, and R 4b System-H; Ring A system, , , , , or; n system 0, 1, or 2; Each R 5 Independently associated with -F, -OH, -CH3, or -O-CH3; R 6 System -H or optionally via a Z 1 Replacement C 1-6 Alkyl, wherein Z 1 It has not been replaced; R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10 aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic system has a 3- to 7-membered heterocyclic group with an additional N; each Z 1 Z 2 、or Z 3 Independently related to deuterium, halogens, O, and C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-15 cycloalkyl, C 6-10 aryl, heterocyclic, heteroaryl, or -OR 3a Z 1 Z 2 、or Z 3 Each alkyl, haloalkyl, alkoxy, haloalkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independently connected to deuterium, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl groups, halogens, -CN, or -S(O)2R 3a Z 1a Each alkyl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent halogens, C 3-15 cycloalkyl, or C 6-10 Aryl, of which Z 1b Each cycloalkyl or aryl group is unsubstituted; each R 3a Independent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one or two 5- to 6-membered heteroaryl groups, each independently of a heteroatom of N or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one or two 3- to 7-membered heterocyclic groups, each independently of a heteroatom of N or O.

10. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 9, wherein R 1 System-H; R 2 -H or -F; R 3 -H or -F; R 4a and R 4b Each system - H; Ring A system, , or; n system 0; R 6 System -H or optionally via a Z 1 Replacement C 1-6 Alkyl, wherein Z 1 It has not been replaced; R 7 Series-H, C 1-6 Alkyl, C 3-10 cycloalkyl or heterocyclic groups, wherein R 7 Each alkyl, cycloalkyl, or heterocyclic group may optionally be derived from one to four identical or different Z groups. 2 Replace; or R 6 and R 7 Together with the attached nitrogen, they form a heterocyclic group, which optionally undergoes one to four identical or different Z-shaped groups. 3 Replace; where R 6 and R 7 The resulting heterocyclic system has a 3- to 7-membered heterocyclic group with an additional N; each Z 1 Z 2 、or Z 3 Independent halogens, =O, C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 3-15 cycloalkyl, heterocyclic, C 6-10 aryl, heteroaryl, or -OR 3a Z 1 Z 2 、or Z 3 Each alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl group may optionally be derived from one to four identical or different Z groups. 1a Replace; Each Z 1a Independent system C 1-9 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl groups, halogens, -CN, or -S(O)2R 3a Z 1a Each alkyl group may optionally be derived from one to four identical or different Z groups. 1b Replace; Each Z 1b Independent halogens, C 3-15 cycloalkyl, or C 6-10 Aryl; of which Z 1b Each cycloalkyl or aryl group is unsubstituted; each R 3a Independent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be derived from one to four identical or different Z groups. 1b Substitution; wherein each heteroaryl group of the compound of formula (I) or formula (Ia) has one or two 5- to 6-membered heteroaryl groups, each independently of a heteroatom of N or S; wherein each heterocyclic group of the compound of formula (I) or formula (Ia) has one or two 3- to 7-membered heterocyclic groups, each independently of a heteroatom of N or O.

11. The compound of any one of claims 1, 2, and 5 to 10, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIa): (IIa).

12. The compound of any one of claims 1, 2, and 5 to 10, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIb): (IIb).

13. The compound of any one of claims 1, 2, and 5 to 10, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIc): (IIc).

14. The compound of any one of claims 1, 2, and 5 to 9, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IId): (IId).

15. The compound of any one of claims 1, 2, and 5 to 9, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIe): (IIe).

16. The compound of any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIf): (IIf).

17. The compound of any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIg): (IIg).

18. The compound of any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIh): (IIh).

19. The compound of any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIi): (IIi).

20. The compound of any one of claims 1, 2, and 5 to 8, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIj): (IIj).

21. The compound of any one of claims 1, 2, and 5 to 8, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is the compound of formula (IIk): (IIk).

22. A compound or a pharmaceutically acceptable salt thereof of any of claims 1 to 4, 6, 8, 9 and 14 to 21, wherein R 4a Series -F, or -CH 3.

23. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 6, 8, 9, and 14 to 22, wherein n is 1 or 2, and each R 5 Independently, it can be -F, -OH, -CH3, or -O-CH3.

24. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 23, wherein R 6 Series-H.

25. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 23, wherein R 6 It is not replaced by C 1-6 alkyl 。 26. The compound of claim 25 or a pharmaceutically acceptable salt thereof, wherein R 6 Series -CH 3 or.

27. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26, wherein R 7 C 1-6 Alkyl or C 3-10 Cycloalkyl groups, each optionally oxidized by one or two halogens or Z 2 C 6-10 Aryl substitution.

28. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 27, wherein R 7 C 1-6 Alkyl or cyclohexyl, each optionally denoted by one or two -F or Z groups. 2 Phenyl substitution.

29. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 28, wherein R 7 System, or.

30. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26, wherein R 7 System, or.

31. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 11 and 14, wherein the compound of formula (I), (IIa) or (IId) is a compound of formula (IIIa): (IIIa).

32. The compound of any one of claims 1, 2, 5 to 10 and 21, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) or (IIk) is a compound of formula (IIIa-1): (IIIa-1).

33. The compound of any one of claims 1, 2, and 5 to 10, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (IIIa-2): (IIIa-2).

34. The compound of any one of claims 1, 2, and 5 to 10, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (IIIa-3): (IIIa-3).

35. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26 and 31 to 34, wherein R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10 aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to three identical or different Z groups. 2 Replacement, in which each Z 2 Independently related to deuterium, halogens, =O, -CN, C 1-8 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 cycloalkyl, C 6-10 aryl, 5 to 12 heteroaryl groups having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or -C(O)-R 3a , where R 3a -H or unsubstituted C 1-6 Alkyl, wherein Z 2 Each C 1-6 Alkyl groups are optionally derived from 1 to 3 Z-axis groups. 1a Replacement, in which each Z 1a Independent cyano or C 1-6 Alkyl group.

36. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26 and 31 to 34, wherein R 7 Series-H, C 1-8 Alkyl, C 3-12 cycloalkyl, C 6-10 aryl, a 4- to 12-membered heterocyclic group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 5- to 12-membered heteroaryl group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, aryl, heterocyclic, or heteroaryl group may optionally be derived from one to three identical or different Z groups. 2 Replacement, in which each Z 2 Independently related to deuterium, halogens, =O, -CN, C 1-8 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 3-10 cycloalkyl, C 6-10 Aryl, or -C(O)-R 3a , where R 3a -H or unsubstituted C 1-6 Alkyl, wherein Z 2 Each C 1-6 Alkyl groups are optionally derived from 1 to 3 Z-axis groups. 1a Replacement, in which each Z 1a Independent cyano or C 1-6 Alkyl group.

37. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26 and 31 to 34, wherein R 7 Series-H, C 1-6 Alkyl, C 3-12 Cycloalkyl, or a 4- to 12-membered heterocyclic group having a heteroatom selected from nitrogen and oxygen, wherein R 7 Each alkyl, cycloalkyl, or heterocyclic group may optionally be connected by one to three identical or different Z-groups. 2 Replacement, in which each Z 2 Independent halogens, =O, C 1-6 Alkyl, C 1-8 Halogenated, C 1-6 alkoxy group, or -C(O)-R 3a , where R 3a -H or unsubstituted C 1-6 alkyl.

38. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26 and 31 to 34, wherein R 7 Series-H, C 1-8 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.3]hexyl, bicyclo[3.1.1]heptyl, spiro[3.3]heptyl, spiro[2.5]octyl, oxalyl, oxy, dialkyl, oxaspiro[3.3]heptyl, oxaspiro[3.5]nonyl, oxabicyclo[3.2.1]octyl, (3aR,6aS)-hexahydro-1H-cyclopent[c]furanyl, bicyclo[3.2.1]octyl, (1R,5S)bicyclo[3.1.0]hexyl, (1R,5S)bicyclo[3.2.0]heptyl, ( 3aR,6aS)-2-methyloctahydrocyclopentadienyl, (1R,5S)-6,6-dimethylbicyclo[3.1.0]hexyl, spiro[2.4]heptyl, 7,7-difluoro-spiro[3.5]nonyl, (4s,7s)-1-oxaspiro[3.5]nonyl, (4r,7r)-oxaspiro[3.5]nonyl, oxabicyclo[2.2.1]heptyl, 3-oxabicyclo[3.2.1]octyl, tetrahydrofuranyl, tetrahydropiperanyl, piperidinyl, tetrahydrothiaranyl, -2,3-dihydro-1H-indene, α, or 4,5,6,7-tetrahydro-1H-indazolyl, each optionally derived from 1 to 3 identical or different Z 2 Replacement, in which each Z 2 Independently, it can be deuterium, =O, -CN, -CH3, -CH2-O-CH3, -CH2-CN, -O-CH3, -O-CF3, -CF3, -OC2H5, -OC3H7, -C(O)-CH3, -F, cyclopropyl, phenyl, triazolyl, or pyridyl.

39. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26 and 31 to 34, wherein R 7 Series-H, C 1-8 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.3]hexyl, bicyclo[3.1.1]heptyl, spiro[3.3]heptyl, spiro[2.5]octyl, oxalyl, oxy, dialkyl, oxaspiro[3.3]heptyl, oxaspiro[3.5]nonyl, oxabicyclo[3.2.1]octyl, (3aR,6aS)-hexahydro-1H-cyclopent[c]furanyl, bicyclo[3.2.1]octyl, (1R,5S)bicyclo[3.1.0]hexyl, (1R,5S)bicyclo[3.2.0]heptyl, ( 3aR,6aS)-2-methyloctahydrocyclopentadienyl, (1R,5S)-6,6-dimethylbicyclo[3.1.0]hexyl, spiro[2.4]heptyl, 7,7-difluoro-spiro[3.5]nonyl, (4s,7s)-1-oxaspiro[3.5]nonyl, (4r,7r)-oxaspiro[3.5]nonyl, oxabicyclo[2.2.1]heptyl, 3-oxabicyclo[3.2.1]octyl, tetrahydrofuranyl, tetrahydropiperanyl, piperidinyl, tetrahydrothiaranyl, -2,3-dihydro-1H-indenyl, α, 4,5,6,7-tetrahydro-1H-indazolyl, each optionally derived from 1 to 3 identical or different Z 2 Replacement, in which each Z 2 Independently, it can be deuterium, =O, -CN, -CH3, -CH2-O-CH3, -CH2-CN, -O-CH3, -O-CF3, -CF3, -OC2H5, -OC3H7, -C(O)-CH3, -F, cyclopropyl, or phenyl.

40. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26 and 31 to 34, wherein R 7 Series-H, C 1-6 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[2.3]hexyl, bicyclo[3.1.1]heptyl, spiro[3.3]heptyl, spiro[2.5]octyl, oxalyl, oxazaspiro[3.3]heptyl, oxazaspiro[3.5]nonyl, oxazabicyclo[3.2.1]octyl, tetrahydrofuranyl, or tetrahydropiperanyl, piperidinyl, or tetrahydrothiaranyl, each optionally derived from 1 to 3 identical or different Z... 2 Replacement, in which each Z 2 Independently defined series = O, -CH 3, -CF 3, -OC 2H 5, -C(O)-CH 3, or -F.

41. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to 26 and 31 to 34, wherein R 7 Department-H、 ... , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or.

42. The compound or its pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26 and 31 to 34, wherein R 7 Department-H、 ... , , , , , , , , , , , , , , , , ,or.

43. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 26 or 31 to 34, wherein R 7 System-H, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or.

44. A compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 11, 14 and 31, wherein the compound of formula (I), (IIa), (IId), or (IIIa) is a compound of formula (IVa): (IVa) wherein q is 1, 2, or 3.

45. A compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 11, 14, 31, and 44, wherein the compound of formula (I), (IIa), (IId), (IIIa), or (IVa) is a compound of formula (IVa-1): (IVa-1) 46. ​​A compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 11, 14, 31, and 44, wherein the compound of formula (I), (IIa), (IId), (IIIa), or (IVa) is a compound of formula (IVa-2): (IVa-2) 47. The compound of claim 44 or a pharmaceutically acceptable salt thereof, wherein q is 1 or 2.

48. The compound of claim 47 or its pharmaceutically acceptable salt, wherein q refers to 1.

49. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 44 to 48, wherein Z 2 System-OR 3a C 3-15 Cycloalkyl groups, 4- to 14-membered heterocyclic groups having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, C 6-10 aryl, 5 to 14 heteroaryl groups having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein each Z 2 Optionally, one to four Z-shaped points, which may be the same or different, can be used. 1a Replacement, in which each Z 1a Independently related to deuterium, cyano, halogen, and C 1-6 Alkyl, C 1-8 Halogenated, C 1-6 Alkyl group, or -S(O)2R 3a And each of them has R 3a Independent system C 1-9 Alkyl or C 6-10 Aryl, wherein R 3a Each alkyl or aryl group may optionally be substituted with one to four halogens.

50. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 44 to 48, wherein Z 2 System-OR 3a Cyclopropyl, cyclobutyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, oxalyl, tetrahydrofuranyl, tetrahydropiperanyl, 1,3-dioxacyclopentyl, phenyl, naphthyl, thiazolyl, pyrazolyl, pyridinyl, or pyryl, each optionally emanated by one or three Z-terminal groups. 1a Replacement, in which each Z 1a Independently, it is a cyano group, -F, -Cl, -O-CH3, -CF3, or phenyl group, and each of the R groups is a cyano group, -F, -Cl, -O-CH3, -CF3, or phenyl group. 3a Independently methyl, ethyl, or phenyl, wherein R 3a Each phenyl group may be optionally substituted with -Cl.

51. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 44 to 48, wherein Z 2 System-OR 3a Cyclopropyl, cyclobutyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, oxalyl, tetrahydrofuranyl, tetrahydropiperanyl, 1,3-dioxacyclopentyl, phenyl, naphthyl, thiazolyl, pyrazolyl, pyridyl, or pyryl, each optionally denoted by one or two Z-terminal groups. 1a Replacement, in which each Z 1a Independently, it consists of cyano, -F, -Cl, -OCH3, -CF3, and each of the R groups... 3a Independently methyl, ethyl, or phenyl, wherein R 3a Each phenyl group may be optionally substituted with -Cl.

52. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 44 to 48, wherein Z 2 System, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or.

53. A compound or a pharmaceutically acceptable salt thereof, as specified in any of claims 44 to 48, wherein Z 2 System, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or.

54. A compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 11, 14, and 31, wherein the compound of formula (I), (IIa), (IId), or (IIIa) is a compound of formula (IVb): , (IVb) wherein each Z 2 They can be the same or different.

55. The compound of claim 54 or its pharmaceutically acceptable salt, wherein each Z may be identical or different. 2 Independent system C 1-6 Alkyl, C 3-15 Cycloalkyl groups, 4- to 14-membered heterocyclic groups having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, C 6-14 Aryl, or C 1-6 Alkoxy groups, each optionally via 1 or 3 Z-terminal groups 1a Replacement, in which each Z 1a Independently related to halogens, cyano groups, =O, and C 1-6 Halogenated, C 3-10 cycloalkyl, or C 6-14 Aryl.

56. The compound of claim 54 or its pharmaceutically acceptable salt, wherein each Z may be identical or different. 2 Independent system C 1-6 Alkyl, C 3-15 Cycloalkyl groups, 4- to 14-membered heterocyclic groups having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, C 6-14 Aryl, or C 1-6 Alkoxy groups, each optionally via 1 or 3 Z-terminal groups 1a Replacement, in which each Z 1a Independently related halogen, cyano, C 1-6 Halogenated, C 3-10 cycloalkyl, C 6-14 Aryl.

57. The compound of claim 54 or its pharmaceutically acceptable salt, wherein each Z may be identical or different. 2 Independent system C 1-6 Alkyl, C 3-15 cycloalkyl, C 6-14 Aryl, or C 1-6 Alkyl group.

58. The compound of claim 54 or its pharmaceutically acceptable salt, wherein each Z may be identical or different. 2 Independently derived from methyl, ethyl, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropiperanyl, bicyclo[1.1.1]pentyl, phenyl, or thiaranyl, each optionally derived from 1 or 3 Z-terminal groups. 1a Replacement, in which each Z 1a Independently associated with -F, -CH3, -CHF2, -CN, =O, or cyclopropyl.

59. The compound of claim 54 or its pharmaceutically acceptable salt, wherein each Z may be identical or different. 2 Independently, it is methyl, ethyl, ethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuranyl, tetrahydropiperanyl, bicyclo[1.1.1]pentyl, or phenyl, each optionally esterified by one or three Z-terminal groups. 1a Replacement, in which each Z 1a Independently associated with -F, -CH3, -CHF2, -CN, or cyclopropyl.

60. The compound of claim 54 or its pharmaceutically acceptable salt, wherein each Z may be identical or different 2 Independently related to -CH3, -C2H5, , , , , , , , , , , , , , , , , or.

61. The compound of claim 54 or its pharmaceutically acceptable salt, wherein each Z may be identical or different. 2 Independently -CH3, -C2H5, , , , , , , , , , , , , , , , or.

62. The compound of claim 54 or its pharmaceutically acceptable salt, wherein each Z may be identical or different. 2 Independently related to -CH 3, , , , or.

63. A compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 11 and 14, wherein the compound of formula (I), (IIa), or (IId) is a compound of formula (IIIb): (IIIb) wherein each p or q, which may be the same or different, is independently 1, 2, or 3.

64. The compound of claim 63 or its pharmaceutically acceptable salt, wherein p and q are each 1.

65. The compound or its pharmaceutically acceptable salt as claimed in paragraphs 63 or 64, wherein each Z may be identical or different. 1 or Z 2 Independent phylogenetic system - H, C 6-10 Aryl, or a 4- to 10-membered heterocyclic group having 1 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur, wherein Z 1 or Z 2 Each of the aryl or heterocyclic groups is unsubstituted.

66. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 63 or 64, wherein each Z may be identical or different. 1 or Z 2 Independently hydrogenated, unsubstituted phenyl, or unsubstituted tetrahydropiperanyl.

67. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 63 or 64, wherein each Z may be identical or different. 1 and Z 2 Independently related, or.

68. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 11 and 14, wherein the compound of formula (I), (IIa), or (IId) is a compound of formula (IIIc): (IIIc).

69. The compound of claim 68 or its pharmaceutically acceptable salt, wherein Z 3 Series-H, C 6-10 aryl, or -OR 3a , where R 3a Series-H, C 1-6 Alkyl, or C 6-10 Aryl, wherein the R 3a Alkyl or aryl groups are each optionally halogenated, C 3-10 cycloalkyl, or C 6-10 Aryl substitution.

70. The compound of claim 68 or a pharmaceutically acceptable salt thereof, wherein Z 3 Methyl, phenyl, or -OR 3a , where R 3a It is methyl, ethyl, or phenyl, wherein R 3a The methyl or phenyl group may be optionally substituted with -Cl, cyclopropyl, or phenyl groups.

71. The compound of claim 68 or a pharmaceutically acceptable salt thereof, wherein Z 3 System, , , , , or.

72. The compound of any one of claims 1, 2, 5 to 11, and 14, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I), (IIa), or (IId) is a compound of formula (IIId): (IIId).

73. The compound of claim 72 or a pharmaceutically acceptable salt thereof, wherein Z 3 System can be selected via Z 1a One of the Cs 6-10 aryl-substituted C 1-6 Alkyl, wherein Z 1a The C 6-10 Aryl optional Z 1b One of the halogens is replaced.

74. The compound of claim 72 or a pharmaceutically acceptable salt thereof, wherein Z 3 System can be selected via Z 1a One of the phenyl-substituted methyl groups, wherein Z 1a The phenyl group can be optionally subjected to Z 1b One of the -Cl substitutions.

75. The compound of claim 72 or a pharmaceutically acceptable salt thereof, wherein Z 3 Tie.

76. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 10, 12 and 15, wherein the compound of formula (I), (IIb) or (IIe) is a compound of formula (IIIe): (IIIe).

77. The compound of claim 76 or a pharmaceutically acceptable salt thereof, wherein R 7 C 1-6 alkyl.

78. The compound of claim 76 or a pharmaceutically acceptable salt thereof, wherein R 7 Tie.

79. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2, 5 to 10, 13 and 16, wherein the compound of formula (I), (IIc) or (IIf) is a compound of formula (IIIf): (IIIf).

80. The compound of claim 79 or a pharmaceutically acceptable salt thereof, wherein R 7 C 1-8 Alkyl, C 3-12 Cycloalkyl, or a 4- to 12-membered heterocyclic group having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 7 Each alkyl, cycloalkyl, or heterocyclic group may optionally be connected by one to three identical or different Z-groups. 2 Replacement, in which each Z 2 Independently related to deuterium, halogens, and carbon 3-10 cycloalkyl, C 1-8 Alkyl, C 1-8 Halogenated, C 1-6 Alkoxy, C 1-6 Haloalkoxy, or a 4- to 12-membered heterocyclic group having one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein Z 2 Each C 1-6 Alkyl groups are optionally derived from 1 to 3 Z-axis groups. 1a Replacement, in which each Z 1a Independent halogen or C 1-6 Alkyl group.

81. The compound of claim 79 or a pharmaceutically acceptable salt thereof, wherein R 7 C 1-8 Alkyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[3.3]heptyl, spiro[2.5]octyl, spiro[3.5]nonyl, tetrahydrofuranyl, tetrahydropiperanyl, oxy, piperidinyl, or tetrahydroindazole, each optionally denoted by one to three identical or different Z-terminal groups. 2 Replacement, in which each Z 2 Independently, it consists of deuterium, -F, -CH3, -CHF2, -CH2-CHF2, -CF3, CH2-CF3, -O-CH3, -O-CHF2, -CH2-O-CH3, -OC3H7, cyclobutyl, oxo-atomyl, or tetrahydropiperanyl, wherein each cyclobutyl, oxo-atomyl, or tetrahydropiperanyl may optionally be substituted with 1 to 3 -F groups.

82. The compound of claim 79 or a pharmaceutically acceptable salt thereof, wherein R 7 C 1-8 Alkyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[3.3]heptyl, spiro[3.5]nonyl, tetrahydrofuranyl, tetrahydropiperanyl, oxy, or piperidinyl, each optionally denoted by one to three identical or different Z-terminal groups. 2 Replacement, in which each Z 2 Independently, it consists of deuterium, -F, -CH3, -CHF2, -CH2-CHF2, -CF3, CH2-CF3, -O-CH3, -O-CHF2, -CH2-O-CH3, -OC3H7, cyclobutyl, oxo-atomyl, or tetrahydropiperanyl, wherein each cyclobutyl, oxo-atomyl, or tetrahydropiperanyl may optionally be substituted with 1 to 3 -F groups.

83. The compound of claim 79 or a pharmaceutically acceptable salt thereof, wherein R 7 C can be optionally substituted with 1 to 3 halogens. 3-12 Cycloalkyl.

84. The compound of claim 79 or a pharmaceutically acceptable salt thereof, wherein R 7 It is a cyclohexyl group optionally substituted with 1 to 3 -F groups.

85. The compound of claim 79 or a pharmaceutically acceptable salt thereof, wherein R 7 System, ...

86. The compound of claim 79 or a pharmaceutically acceptable salt thereof, wherein R 7 System, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or.

87. The compound of claim 79 or a pharmaceutically acceptable salt thereof, wherein R 7 System, or.

88. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 10, wherein R 1 Deuterium.

89. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 88, wherein R 2 The series is -H or -F.

90. The compound of claim 89 or a pharmaceutically acceptable salt thereof, wherein R 2 Series-H.

91. The compound of claim 89 or a pharmaceutically acceptable salt thereof, wherein R 2 Series-F.

92. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1 to 91, wherein R 3 The series is -H or -F.

93. The compound of claim 92 or a pharmaceutically acceptable salt thereof, wherein R 3 Series-H.

94. The compound of claim 92 or a pharmaceutically acceptable salt thereof, wherein R 3 Series-F.

95. The compound or its pharmaceutically acceptable salt thereof of any one of claims 1 to 9, 14 to 30, and 35 to 43, wherein R 4a and R 4b Each is a hydrogen atom.

96. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (V): , (V) wherein R 2 -H or -F; R 21 -H or -F; R 3 -H or -F; R 7 C 1-8 Alkyl or C 3-12 cycloalkyl, wherein R 7 Each alkyl or cycloalkyl group may optionally be derived from one to four identical or different Z groups. 2 Replacement; and each Z 2 Independently related to deuterium, halogens, and carbon 1-3 Alkyl, C 1-3 Halogenated, or C 6-10 Aryl.

97. The compound of claim 96 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (V) is a compound of formula (Va): , (Va) 98. The compound or its pharmaceutically acceptable salt as claimed in claim 96 or 97, wherein R 2 System-H;R 21 System -H; and R 3 The series is -H or -F.

99. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 96 to 98, wherein R 7 C 1-8 Alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.3]hexyl, bicyclo[3.1.1]heptyl, spiro[3.3]heptyl, spiro[2.5]octyl, bicyclo[3.2.1]octyl, (1R,5S)bicyclo[3.1.0]hexyl, (1R,5S)bicyclo[3.2.0]heptyl, spiro[2.4]heptyl, each optionally derived from 1 to 3 identical or different Z... 2 Replacement, in which each Z 2 Independently, it can be deuterium, -CH3, -C2F, -CHF2, -CF3, -F, or phenyl.

100. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 96 to 98, wherein R 7 C 1-3 Alkyl or cyclohexyl groups, each optionally fused with one or two identical or different Z groups. 2 Replacement, in which each Z 2 Independently related to -F or phenyl.

101. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 96 to 98, wherein R 7 System, ...

102. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 96 to 98, wherein R 7 System, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or.

103. The compound of claim 96 or a pharmaceutically acceptable salt thereof, wherein the compound is, ...

104. The compound of claim 96 or a pharmaceutically acceptable salt thereof, wherein the compound is, , , , , , , , , , or.

105. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is a compound of formula (VI): , (VI) wherein R 7 The system can optionally be traversed by one to four Z-shaped elements, which may be the same or different. 2 Replacement C 3-12 cycloalkyl groups; and each Z 2 Independently related to deuterium, halogens, and carbon 1-3 Alkyl, C 1-3 Halogenated groups.

106. The compound of claim 105 or a pharmaceutically acceptable salt thereof, wherein the compound of formula (VI) is a compound of formula (VIa): , (VIa) 107. The compound or its pharmaceutically acceptable salt as claimed in claims 105 or 106, wherein R 7 The system can be optionally connected via 1 to 4 Z-types, which may be the same or different. 2 Substituted cyclohexyl groups, wherein each Z 2 Independently, it can be deuterium, -CH3, -C2F, -CHF2, -CF3, or -F.

108. The compound of claim 105 or a pharmaceutically acceptable salt thereof, wherein the compound is, , , , , , , , , , , , , , , , , , , , , , , , , , or.

109. The compound of claim 105 or a pharmaceutically acceptable salt thereof, wherein the compound is, , , , , , , , , , or.

110. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, and 31, wherein the compound is, or.

111. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, and 31, wherein the compound is, ... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,or.

112. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 21, or 32, wherein the compound is, ...

113. The compound of claim 1 or 14 or its pharmaceutically acceptable salt, wherein the compound is, , , , , , , , , , , , , or.

114. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, and 63, wherein the compound is, , , , , , or.

115. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, and 68, wherein the compound is, , , , , , or.

116. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 12, 15 and 76, wherein the compound is...

117. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 13, 16 and 79, wherein the compound is, , or .

118. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 13, 16 and 79, wherein the compound is, or.

119. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 13, 16 and 79, wherein the compound is, , , , , , , , , , , , , , or.

120. The compound of claim 1 or 17 or a pharmaceutically acceptable salt thereof, wherein the compound is...

121. The compound of claim 1 or 20 or a pharmaceutically acceptable salt thereof, wherein the compound is...

122. The compound of claim 1 or 18 or a pharmaceutically acceptable salt thereof, wherein the compound is...

123. The compound of claim 1 or 19 or a pharmaceutically acceptable salt thereof, wherein the compound is...

124. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, 14, 32, and 96, wherein the compound is...

125. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, 14, 32 and 96, wherein the compound is...

126. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 3, 11, 14, 32, 33, and 96, wherein the compound is...

127. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 4, 11, 14, 32, 34 and 96, wherein the compound is...

128. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 14, 32, 34 and 96, wherein the compound is...

129. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, 14, 32 and 96, wherein the compound is...

130. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, 14, 32 and 96, wherein the compound is...

131. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 11, 14, 32 and 96, wherein the compound is...

132. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 11, 14, 32 and 96, wherein the compound is...

133. A compound or a pharmaceutically acceptable salt thereof, as claimed in any of claims 1, 11, 14, 32, and 96, wherein the compound is...

134. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 13 and 16, wherein the compound is...

135. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 13 and 16, wherein the compound is...

136. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 11, 14, 32 and 96, wherein the compound is...

137. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 13 and 16, wherein the compound is...

138. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 13 and 16, wherein the compound is...

139. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 13 and 16, wherein the compound is...

140. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 13 and 16, wherein the compound is...

141. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 13 and 16, wherein the compound is...

142. A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of claims 1 to 141, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

143. The pharmaceutical composition of claim 142 further includes additional therapeutic agents.

144. A method of treating IKFZ2 protein-related diseases or conditions, comprising administering to a patient in need a therapeutically effective amount of any one of claims 1 to 141, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as claimed in claims 142 or 143.

145. The method of claim 144, wherein the IKFZ2-related disease or condition is cancer.

146. The method of claim 145, wherein the cancer is a blood cancer selected from acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), B-cell ALL, myelodysplastic syndrome (MDS), myeloproliferative disorders (MPD), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), undifferentiated leukemia, small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), T-cell lymphoma, B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL), Waldestrom macroglobulinemia (WM), and multiple myeloma (MM).

147. The method of claim 145, wherein the cancer is a solid tumor and is selected from lung cancer, colorectal cancer, gastric cancer, kidney cancer, ovarian cancer, testicular cancer, uterine cancer, bladder cancer, breast cancer, prostate cancer, cervical cancer, pancreatic cancer, and head and neck cancer.

148. The method of any of claims 144 to 147, wherein the compound or a pharmaceutically acceptable salt thereof is administered in combination with an additional therapeutic agent or mode of treatment.

149. The pharmaceutical composition of claim 143 or the method of claim 148, wherein the additional therapeutic agent or additional treatment method comprises one, two, three, or four additional therapeutic agents and / or treatment methods.

150. A pharmaceutical composition as claimed in claim 143 or 149, or a method as claimed in claim 148 or 149, wherein the additional therapeutic agent or mode of treatment is selected from immune checkpoint modulators, antibody-drug conjugates (ADCs), anti-apoptotic agents, targeted anticancer therapies, chemotherapy agents, surgery, or radiotherapy.

151. The pharmaceutical composition or method of claim 150, wherein the immune checkpoint modulator is selected from anti-PD-(L)1 antibody, anti-TIGIT antibody, anti-CTLA4 antibody, anti-CCR8 antibody, anti-TREM1 antibody, anti-TREM2 antibody, CD47 inhibitor, DGKa inhibitor, HPK1 inhibitor, FLT3 agonist, adenosine receptor antagonist, CD39 inhibitor, CD73 inhibitor, IL-2 variant (IL-2v), and CAR-T cell therapy.

152. A pharmaceutical composition or method as claimed in claim 151, wherein the anti-PD-(L)1 anti-system is selected from pembrolizumab, nivolumab, cemiplimab, pidilizumab, spartalizumab, atezolizumab, avelumab, durvalumab, cosibelimab, sasanlimab, tislelizumab, and retifan. The following are listed: limab, balstilimab, toripalimab, cetrelimab, genolimzumab, prolgolimab, lodapolimab, camrelizumab, budigalimab, avelumab, dostarlimab, envafolimab, sintilimab, and zimberelimab.

153. The pharmaceutical composition or method of claim 151, wherein the anti-TIGIT anti-system is selected from tiragolumab, vibostolimab, domvanalimab, AB308, AK127, BMS-986207, and etigilimab.

154. The pharmaceutical composition or method of claim 151, wherein the anti-CTLA4 anti-system is selected from ipilimumab, tremelimumab, and zalifrelimab.

155. The pharmaceutical composition or method of claim 151, wherein the CD47 inhibitor is selected from magrolimab, letaplimab, lemzoparlimab, AL-008, RRx-001, CTX-5861, FSI-189 (GS-0189), ES-004, BI-765063, ADU1805, CC-95251, and Q-1801.

156. The pharmaceutical composition or method of claim 151, wherein the adenosine receptor antagonist is etrumadenant (AB928), taminadenant, TT-10, TT-4, or M1069.

157. The pharmaceutical composition or method of claim 151, wherein the CD39 inhibitor is TTX-030.

158. The pharmaceutical composition or method of claim 151, wherein the CD73 inhibitor is quemliclustat (AB680), uliledlimab, mupadolimab, ORIC-533, ATG-037, PT-199, AK131, NZV930, BMS-986179, or oleclumab.

159. The pharmaceutical composition or method of claim 151, wherein the IL-2v is aldesleukin (Proleukin), beempegaldesleukin (NKTR-214), nemvaleukin alfa (ALKS-4230), THOR-202 (SAR-444245), BNT-151, ANV-419, XTX-202, RG-6279 (RO-7284755), NL-201, STK-012, SHR-1916, or GS-4528.

160. The pharmaceutical composition or method of claim 151, wherein the ADC is selected from sacituzumab govitecan, datopotamab deruxtecan, enfortumab vedotin, and trastuzumab deruxtecan.

161. A pharmaceutical composition or method as claimed in claim 151, wherein the additional therapeutic agent is selected from idealisib, sacituzumab govitecan, magrolimab, GS-0189, GS-3583, zimberelimab, GS-4224, GS-9716, GS-6451, GS-9911, GS-1811 (JTX-1811), quemliclustat (Ab680), etrumadenant (AB928), domvanalimab, AB308, PY159, PY314, AGEN-1223, AGEN-2373, axicabtagene ciloleucel, and brexucabtagene. autoleucel).

162. Use of a compound of any one of claims 1 to 141 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of IKFZ2-related diseases or conditions.

163. A compound of any one of claims 1 to 141 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition of claims 142 or 143, for medical use.

164. A compound of any one of claims 1 to 141, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claims 142 or 143, for the treatment of cancer.