Capsid inhibitors for the treatment of HIV

Abstract

To provide a method for treating a disease. [Solution] This disclosure generally relates to a particular compound, a pharmaceutical composition containing the compound, and a method for producing and using the compound and the pharmaceutical composition. The compounds and compositions disclosed herein may be used for the treatment or prevention of retroviral infections, including infections caused by the HIV virus. In one embodiment, a pharmaceutical composition is provided herein comprising the compound provided herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of the compound provided herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 044,086, filed on 25 June 2020, which is incorporated herein by reference in its entirety for all purposes. (Cross-reference of related applications) This disclosure relates, in general terms, to novel compounds, pharmaceutical compositions containing such compounds, and methods for producing and using such compounds and pharmaceutical compositions. In some embodiments, the novel compounds provided herein may be used to treat retroviral infections, including infections caused by the HIV virus. [Background technology]

[0002] Positive-sense single-stranded RNA viruses, including the retroviridae family, encompass the subfamily orthoretroviruses and the genera alpha-retroviruses, beta-retroviruses, gamma-retroviruses, delta-retroviruses, epsilon-retroviruses, lentiviruses, and spumaviruses, which cause many diseases in humans and animals. Human infection with HIV-1, a lentivirus, leads to T helper cell depletion and immunodeficiency, resulting in immunodeficiency and increased susceptibility to opportunistic infections. Treatment of HIV-1 infection with highly active antiretroviral therapy (HAART) has been shown to be effective in reducing the viral load and significantly slowing disease progression (Hammer, SM, et al.; JAMA 2008, 300:555-570). However, these treatments may lead to the emergence of HIV strains resistant to current therapies (Taiwo, B., International Journal of Infectious Diseases 2009, 13:552-559; Smith, RJ, et al., Science 2010, 327:697-701). Therefore, there is an urgent need for the discovery of new antiretroviral agents that are active against newly drug-resistant HIV variants. Compounds that are potent, stable, and exhibit improved pharmacokinetic and / or pharmacodynamic profiles are needed for the treatment of retroviral infections, including HIV infections. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Hammer,SM,et al.;JAMA 2008,300:555-570 [Non-Patent Document 2] Taiwo, B., International Journal of Infectious Diseases 2009,13:552-559 [Non-Patent Document 3] Smith,RJ,et al.,Science 2010,327:697-701

Summary of the Invention

Means for Solving the Problems

[0004] In one aspect, provided herein is a compound of formula I,

Chemical Formula

[0005] In one embodiment, a pharmaceutical composition comprising a compound provided herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier is provided herein. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of a compound provided herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

[0006] In some embodiments, the pharmaceutical composition provided herein further comprises one or more (i.e., 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 (i.e., one, two, three, four; one or two; one to three; or one to four) additional therapeutic agents or pharmaceutically acceptable salts thereof.

[0007] In one embodiment, the present disclosure provides a method for treating or preventing human immunodeficiency virus (HIV) infection in a subject requiring such treatment, comprising administering a therapeutically effective amount of a compound provided herein (i.e., a compound of formula I, Ia, II, or IIa), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition provided herein, to the subject. [Modes for carrying out the invention]

[0008] I. Definition The following description is made with the understanding that this disclosure should be considered as an illustration of the claimed subject matter and that the attached claims are not intended to limit the scope of the specific embodiments illustrated. The headings used throughout this disclosure are for convenience only and should not be construed as limiting the scope of the claims. Embodiments illustrated under any heading may be combined with embodiments illustrated under any other heading.

[0009] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Note that, as used herein and in the appended claims, the singular forms “a,” “and,” and “the” refer to multiple subjects unless otherwise explicitly indicated in the context. Thus, for example, a reference to “compound” includes multiple such compounds, and a reference to “assay” includes one or more assays and their equivalents known to those skilled in the art.

[0010] When used in this disclosure, the following words, phrases, and symbols are generally intended to have the meanings revealed below, unless the context in which they are used indicates otherwise.

[0011] A dash ("-") that is not between two letters or symbols is used to indicate a bonding point for a substituent. For example, -CONH2 is bonded via a carbon atom. Dashes at the beginning or end of a chemical group are for convenience only, and the chemical group may be shown with or without one or more dashes without losing their usual meaning. A wavy line drawn across a line in the structure indicates a bonding point of a group. Unless chemically or structurally required, the order in which chemical groups are written or named does not indicate or imply direction. A solid line protruding from the center of a ring indicates that the bonding point of a substituent in that ring may be on any ring atom. For example, R in the following structure aIt may be bonded to any of the five carbon ring atoms, or the hydrogen bonded to the nitrogen ring atom may be R a It can be replaced with: [ka]

[0012] "C u~v The prefix "" indicates that the following group has u to v carbon atoms. For example, "C 1~6 The term "alkyl group" indicates that the alkyl group has 1 to 6 carbon atoms. Similarly, the term "x-y membered" ring, where x and y are numerical ranges (e.g., "3-12 membered heterocyclyl"), means a ring having x to y atoms (i.e., 3 to 12 atoms), of which up to 80% may be heteroatoms such as N, O, S, and P, and the remaining atoms are carbon.

[0013] In addition, certain commonly used alternative chemical names may or may not be used. For example, divalent groups such as divalent "alkyl" groups and divalent "aryl" groups may also be called "alkylene" groups or "alkylenyl" groups or alkylyl groups, respectively, or "arylene" groups or "aryrenyl" groups or arylyl groups.

[0014] "The compounds disclosed herein" or "the compounds of this disclosure" or "the compounds provided herein" or "the compounds described herein" are compounds of formulas I, II, IIa, III, IV, and This refers to compounds of / or V. It also includes specific compounds from Examples 1 to 195.

[0015] References to values ​​or parameters "about" in this specification include (and are described) embodiments relating to the value or parameter itself. In certain embodiments, the term "about" includes the indicated amount ± 10%. In other embodiments, the term "about" includes the indicated amount ± 5%. In certain other embodiments, the term "about" includes the indicated amount ± 1%. The term "about X" also includes a description of "X".

[0016] "Alkyl" refers to an unbranched or branched saturated hydrocarbon chain. As used herein, alkyl has 1 to 20 carbon atoms (i.e., C 1~20 Alkyl), having 1 to 12 carbon atoms (i.e., C 1~12 Alkyl), having 1 to 8 carbon atoms (i.e., C 1~8 Alkyl), having 1 to 6 carbon atoms (i.e., C 1~6 Alkyl), having 1 to 4 carbon atoms (i.e., C 1~4 Alkyl), having 1 to 3 carbon atoms (i.e., C 1~3 Alkyl) or having 1-2 carbon atoms (i.e., C 1~2 Alkyl). Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl group having a specific number of carbon atoms is designated by its chemical name or identified by its molecular formula, all positional isomers having that number of carbon atoms can be included. For example, "butyl" includes n-butyl (i.e., -(CH2)3CH3), sec-butyl (i.e., -CH(CH3)CH2CH3), isobutyl (i.e., -CH2CH(CH3)2), and tert-butyl (i.e., -C(CH3)3), and "propyl" includes n-propyl (i.e., -(CH2)2CH3) and isopropyl (i.e., -CH(CH3)2).

[0017] "Alkenyl" contains at least one carbon-carbon double bond and has 2 to 20 carbon atoms (i.e., C 2~20 Alkenyls) have 2 to 8 carbon atoms (i.e., C 2~8 Alkenyls), having 2 to 6 carbon atoms (i.e., C 2~6 Alkenyl) or having 2 to 4 carbon atoms (i.e., C 2~4Alkenyl refers to an aliphatic group. Examples of alkenyl groups include ethenyl, propenyl, and butadienyl (including 1,2-butadienyl and 1,3-butadienyl).

[0018] "Alkynyl" contains at least one carbon-carbon triple bond and has 2 to 20 carbon atoms (i.e., C 2~20 Alkynyl) has 2 to 8 carbon atoms (i.e., C 2~8 Alkynyl) has 2 to 6 carbon atoms (i.e., C 2~6 Alkynyl) or having 2 to 4 carbon atoms (i.e., C 2~4 Alkynyl refers to an aliphatic group. The term "alkynyl" also includes alkynyl groups that have one triple bond and one double bond.

[0019] "Alkylene" refers to a divalent, unbranched, saturated hydrocarbon chain. As used herein, alkylene has 1 to 20 carbon atoms (i.e., C 1~20 Alkylenes), having 1 to 12 carbon atoms (i.e., C 1~12 Alkylenes), having 1 to 8 carbon atoms (i.e., C 1~8 Alkylenes), having 1 to 6 carbon atoms (i.e., C 1~6 Alkylenes), having 1 to 4 carbon atoms (i.e., C 1~4 Alkylenes), having 1 to 3 carbon atoms (i.e., C 1~3 Alkylene), or having 1-2 carbon atoms (i.e., C 1~2 Alkylenes). Examples of alkylene groups include methylene, ethylene, propylene, butylene, pentylene, and hexylene. In some embodiments, the alkylene is optionally substituted with an alkyl group. Substituted alkylene groups include -CH(CH3)CH2-, -CH2CH(CH3)-, and -CH2C Examples include H(CH2CH3)-, -CH2C(CH3)2-, -C(CH3)2CH2-, -CH(CH3)CH(CH3)-, -CH2C(CH2CH3)(CH3)-, and -CH2C(CH2CH3)2.

[0020] "Alkoxy" refers to an alkyl-O- group. Examples of alkoxy groups include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy. "Haloalkoxy" refers to the alkoxy groups defined above, in which one or more hydrogen atoms are replaced by halogens.

[0021] "Acyl" refers to a -C(=O)R group, where R is hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroalkyl, or heteroaryl, each of which may be substituted as defined herein. Examples of acyls include formyl, acetyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, and benzoyl.

[0022] "Amid" is -C(=O)NR y R z The "C-amide" group and -NR refer to the group. y C(=O)R z It refers to both the "N-amide group" and the group, and in the formula, R y and R z Each of these is independently selected from the group consisting of hydrogen, alkyl, aryl, haloalkyl, heteroaryl, cycloalkyl, or heterocyclyl, each of which may be optionally substituted.

[0023] "Amino" is -NR y R z It refers to the base, and in the formula, R y and R z Each of these is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, or heterocyclyl, and each of them may optionally be substituted.

[0024] "Aryl" refers to an aromatic carbocyclic group having a monocyclic (e.g., monocyclic) or a polycyclic (e.g., bicyclic or tricyclic) system including a condensed system. As used herein, aryl has 6 to 20 ring carbon atoms (i.e., C 6~20 aryl), having 6 to 12 carbocyclic atoms (i.e., C 6~12 aryl), or having 6 to 10 carbon ring atoms (i.e., C 6~10 (aryl). Examples of aryl groups include phenyl, naphthyl, fluorenyl, and anthryl. However, aryl does not in any way encompass, nor overlap with, the heteroaryls as defined below. When one or more aryl groups are fused with a heteroaryl ring, the resulting ring system is a heteroaryl.

[0025] "Cyano" or "carbonitrile" refers to the -CN group.

[0026] "Cycloalkyl" refers to saturated or partially saturated cyclic alkyl groups having monocyclic or polycyclic structures, including condensed ring systems, bridged ring systems, and spirocyclic systems. The term "cycloalkyl" includes a cycloalkenyl group (i.e., a cyclic group having at least one double bond). As used herein, cycloalkyl has 3 to 20 ring carbon atoms (i.e., C 3~20 Cycloalkyl), having 3 to 12 ring carbon atoms (i.e., C 3~12 Cycloalkyl), having 3 to 10 ring carbon atoms (i.e., C 3~10 Cycloalkyl), having 3 to 8 ring carbon atoms (i.e., C 3~8 (Cycloalkyl), or having 3 to 6 ring carbon atoms (i.e., C 3~6 Cycloalkyl groups. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0027] "Bridged" refers to a ring in which non-adjacent atoms on the ring are bonded by divalent substituents such as an alkylenyl group, an alkylenyl group containing one or two heteroatoms, or a single heteroatom. This refers to condensation. Quinuclidinyl and admantanyl are examples of cross-linking ring systems.

[0028] The term "condensation" refers to rings that are bonded to adjacent rings.

[0029] "Spiro" refers to a ring substituent that is bonded by two bonds at the same carbon atom. Examples of spiro groups include 1,1-diethylcyclopentane, dimethyl-dioxolane, and 4-benzyl-4-methylpiperidine, where cyclopentane and piperidine are spiro substituents, respectively.

[0030] "Halogen" or "halo" includes fluoro, chloro, bromo, and iodine. "Haloalkyl" refers to the previously defined unbranched or branched alkyl groups in which one or more hydrogen atoms are replaced by halogens. For example, if a residue is substituted with two or more halogens, it can be referred to by using a prefix corresponding to the number of halogenated moieties. Dihaloalkyl and trihaloalkyl refer to alkyl groups substituted with two ("di") or three ("tri") halo groups, which may but are not necessarily the same halogen. Examples of haloalkyls include difluoromethyl (-CHF2) and trifluoromethyl (-CF3).

[0031] "Heteroalkylene" refers to a divalent, unbranched, saturated hydrocarbon chain having one, two, or three heteroatoms selected from NH, O, or S. As used herein, heteroalkylene has 1 to 20 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C 1~20 Heteroalkylenes) have 1 to 8 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C 1~8 Heteroalkylenes) have 1 to 6 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C 1~6Heteroalkylenes) have 1 to 4 carbon atoms and one, two, or three heteroatoms selected from NH, O, and S (i.e., C 1~4 Heteroalkylenes) have 1 to 3 carbon atoms and 1, 2, or 3 heteroatoms selected from NH, O, and S (i.e., C 1~3 Heteroalkylenes), or having 1-2 carbon atoms and 1, 2, or 3 heteroatoms selected from NH, O, and S (i.e., C 1~3 (Heteroalkylenes). For example, -CH2O- is a C1 heteroalkylene, and -CH2SCH2- is a C2 heteroalkylene. Examples of heteroalkylene groups include -CH2CH2OCH2-, -CH2SCH2OCH2-, -CH2O-, and -CH2NHCH2-. In some embodiments, the heteroalkylene is optionally substituted with an alkyl group. Examples of substituted heteroalkylene groups include -CH(CH3)N(CH3)CH2-, -CH2OCH(CH3)-, -CH2CH(CH2CH3)S-, -CH2NHC(CH3)2-, -C(CH3)2SCH2-, -CH(CH3)N(CH3)CH(CH3)O-, -CH2SC(CH2CH3)(CH3)-, and -CH2C(CH2CH3)2NH-.

[0032] "Heteroaryl" refers to an aromatic group having a monocyclic, polycyclic, or fused polycyclic structure with one or more ring heteroatoms independently selected from nitrogen, oxygen, and sulfur. As used herein, heteroaryl refers to a group having 1 to 20 carbocyclic atoms (i.e., C 1~20 Heteroaryl), 3 to 12 carbon ring atoms (i.e., C 3~12 Heteroaryl) or 3 to 8 carbon ring atoms (i.e., C 3~8 A heteroaryl group contains 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom, which are independently selected from nitrogen, oxygen, and sulfur. Examples of heteroaryl groups include pyrimidinyl, prinyl, pyridyl, pyridazinyl, benzothiazolyl, and pyrazolyl. A heteroaryl is an aryl group as defined above. It does not include and does not overlap with the aryl.

[0033] "Heterocyclyl," "heterocyclic ring," or "heterocycle" refers to a non-aromatic cyclic alkyl group having one or more ring heteroatoms independently selected from nitrogen, oxygen, and sulfur. As used herein, "heterocyclyl," "heterocyclic ring," or "heterocycle" refers to a saturated or partially saturated ring unless otherwise specified. For example, in some embodiments, "heterocyclyl," "heterocyclic ring," or "heterocycle" refers to a partially saturated ring when specified. The term "heterocyclyl," "heterocyclic ring," or "heterocycle" includes a heterocycloalkenyl group (i.e., a heterocyclyl group having at least one double bond). A heterocyclyl may be monocyclic or polycyclic, and the polycyclic may be condensed, bridged, or spiro. As used herein, a heterocyclyl has 2 to 20 carbon ring atoms (i.e., C 2~20 Heterocyclines) have 2 to 12 carbon ring atoms (i.e., C 2~12 Heterocyclines) have 2 to 10 carbon ring atoms (i.e., C 2~10 Heterocyclines) have 2 to 8 carbon ring atoms (i.e., C 2~8 Heterocyclines) have 3 to 12 carbon ring atoms (i.e., C 3~12 Heterocyclyls have 3 to 8 carbon ring atoms (i.e., C 3~8 Heterocyclyl), or having 3 to 6 carbon ring atoms (i.e., C 3~6Heterocyclyls; having 1 to 5 ring heteroatoms, 1 to 4 ring heteroatoms, 1 to 3 ring heteroatoms, 1 to 2 ring heteroatoms, or 1 ring heteroatom independently selected from nitrogen, sulfur, or oxygen. Examples of heterocyclyl groups include pyrrolidinyl, piperidinyl, piperazinyl, oxetanyl, dioxolanil, azetidinyl, and morpholinyl. As used herein, the term "bridged heterocyclyl" refers to a 4 to 10-membered ring moiety of a heterocyclyl having one or more (e.g., one or two) 4 to 10-membered ring moieties, where each heteroatom is independently linked to at least one heteroatom selected from nitrogen, oxygen, and sulfur at two non-adjacent atoms. As used herein, "bridged heterocyclyl" includes bicyclic and tricyclic ring systems. As used herein, the term “spiroheterocyclyl” refers to a ring system in which a 3- to 10-membered heterocyclyl has one or more additional rings, where the one or more additional rings are 3- to 10-membered cycloalkyl or 3- to 10-membered heterocyclyl, and a single atom of the one or more additional rings is also an atom of the 3- to 10-membered heterocyclyl. Examples of spiroheterocyclyls include bicyclic and tricyclic ring systems such as 2-oxa-7-azaspiro[3.5]nonanyl, 2-oxa-6-azaspiro[3.4]octanyl, and 6-oxa-1-azaspiro[3.3]heptanyl. As used herein, the terms “heterocyclic,” “heterocyclyl,” and “heterocyclic ring” are used interchangeably. In some embodiments, the heterocyclyl is substituted with an oxo group.

[0034] "Hydroxy" or "hydroxyl" refers to the -OH group.

[0035] "Oxo" refers to an (=O) group or an (O) group.

[0036] "Sulfonyl" is -S(O)2R c It refers to the base, and in the formula, R cThese are alkyl, haloalkyl, heterocyclyl, cycloalkyl, heteroaryl, or aryl compounds. Examples of sulfonyl compounds include methylsulfonyl, ethylsulfonyl, phenylsulfonyl, and toluenesulfonyl.

[0037] As used herein, "2-oxa-6-azaspiro[3.3]heptane" has the following structure: [ka]

[0038] As used herein, "2,5-diazabicyclo[2.2.1]heptane" has the following structure: [ka]

[0039] As used herein, "2,6-diazaspiro[3.3]heptane" has the following structure: [ka]

[0040] As used herein, "1,6-diazaspiro[3.3]heptane" has the following structure: [ka]

[0041] As used herein, "2,7-diazaspiro[3.5]nonane" has the following structure: [ka]

[0042] As used herein, "1-oxa-3,8-diazaspiro[4.5]decane" has the following structure: [ka]

[0043] As used herein, "5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine" has the following structure: [ka]

[0044] As used herein, "2,3-dihydrobenzo[b][1,4]dioxin" has the following structure: [ka]

[0045] As used herein, "1H-benzo[d]imidazole" has the following structure: ru. [ka]

[0046] Whenever a diagram of a group ends with a single bonded nitrogen atom, that group represents an -NH group unless otherwise specified. Similarly, unless otherwise specified, hydrogen atoms(s) are implied to be present and assumed to be present where necessary, taking into account the knowledge of those skilled in the art, to complete the valence or provide stability.

[0047] The terms "optional" or "optionally" mean that the event or situation described thereafter may or may not occur, and that the description includes both the cases in which such event or situation occurs and the cases in which it does not occur. Furthermore, the term "optionally substituted" means that one or more hydrogen atoms on a specified atom or group may or may not be replaced by a non-hydrogen part.

[0048] The term "substituted" means that one or more hydrogen atoms on a given atom or group are replaced by one or more substituents other than hydrogen, provided that the normal valence of the given atom is not exceeded. Examples of one or more substituents include, but are not limited to, alkyl, alkenyl, alkynyl, alkoxy, acyl, amino, amide, amidino, aryl, azide, carbamoyl, carboxyl, carboxyl ester, cyano, guanidino, halo, haloalkyl, heteroalkyl, heteroaryl, heterocyclyl, hydroxy, hydrazino, imino, oxo, nitro, alkylsulfinyl, sulfonic acid, alkylsulfonyl, thiocyanate, thiol, thion, or combinations thereof. Polymers or similar non-specific structures obtained by defining substituents with an infinitely many additional substituents (e.g., substituted aryls having a substituted alkyl, where the substituted alkyl itself is substituted with a substituted aryl group, which is further substituted with a substituted heteroalkyl group, etc.) are not intended to be included herein. Unless otherwise stated, the maximum number of consecutive substitutions in the compounds described herein is three. For example, consecutive substitution of a substituted aryl group with two other substituted aryl groups is limited to ((substituted aryl)substituted aryl)substituted aryl. Similarly, the above definitions are not intended to include unacceptable substitution patterns (e.g., methyl substituted with five fluorine or heteroaryl groups having two adjacent oxygen ring atoms). Such unacceptable substitution patterns are well known to those skilled in the art. When used to modify a chemical group, the term “substituted” can describe other chemical groups as defined herein. For example, the term “substituted aryl” includes, but is not limited to, “alkylaryl.” Unless otherwise specified, where a group is described as optionally substituted, any substituent on the group is itself unsubstituted.

[0049] In some embodiments, the substituted cycloalkyl, substituted heterocyclyl, substituted aryl, and / or substituted heteroaryl comprises cycloalkyl, heterocyclyl, aryl, and / or heteroaryl having substituents on the ring atom, and the cycloalkyl, heterocyclyl, aryl, and / or heteroaryl are bonded to the remainder of the compound. For example, in the following portion, cyclopropyl is substituted with a methyl group: [ka]

[0050] The compounds of the embodiments disclosed herein, or their pharmaceutically acceptable salts, may contain one or more chiral centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined as (R)- or (S)- with respect to absolute stereochemistry, or as (D)- or (L)- with respect to amino acids. This disclosure includes all such possible isomers, as well as their racemic and optically pure forms. Optically active (+) and (-), (R)- and (S)-, or (D)- and (L)- isomers may be prepared using chiral synthons or chiral reagents, or they may be divided using conventional techniques, such as chromatography and fractional crystallization. Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from suitable optically pure precursors, or the division of racemic compounds (or racemic compounds of salts or derivatives) using, for example, chiral high-pressure liquid chromatography (HPLC). When the compounds described herein contain an olefinic double bond or other geometrically asymmetric center, and unless otherwise specified, these compounds are intended to include both E and Z geometric isomers. Similarly, all tautomer forms are also intended to be included. When compounds are represented in their chiral form, embodiments are understood to include, but not be limited to, specific diastereomeric or enantiomerically enriched forms. When chirality is not specified but present, embodiments are understood to cover either specific diastereomeric or enantiomerically enriched forms, or racemic or scaremic mixtures of such compounds. As used herein, “scaremic mixture” is a mixture of stereoisomers in a ratio other than 1:1.

[0051] A "stereoisomer" refers to a compound that has the same atoms bonded together by the same bonds but has different three-dimensional structures that are not interchangeable. This disclosure intends various stereoisomers and mixtures thereof, and includes "enantiomers," which refer to two stereoisomers whose molecules are mirror images of each other and cannot be superimposed.

[0052] Enantiomers are a pair of stereoisomers that are mirror images of each other and cannot be superimposed. A 1:1 mixture of enantiomers is a racemic mixture. A mixture of enantiomers in a ratio other than 1:1 is a scaremic mixture.

[0053] A "diastereoisomer" is a stereoisomer that has at least two chiral atoms but is not a mirror image of each other.

[0054] "Tautomerism" refers to the transfer of a proton from one atom of a molecule to another atom of the same molecule. This disclosure includes tautomers of any compound provided herein.

[0055] Some of the compounds provided herein exist as tautomeric isomers. Tautomeric isomers exist in equilibrium with each other. For example, an amide-containing compound may exist in equilibrium with an imido acid tautomer. Regardless of which tautomer is shown and regardless of the nature of the equilibrium between the tautomers, it will be understood by those skilled in the art that a compound contains both an amide and an imido acid tautomer. Thus, an amide-containing compound is understood to contain its imido acid tautomer. Similarly, an imido acid-containing compound is understood to contain its amide tautomer.

[0056] A "solvate" is formed by the interaction of a solvent and a compound. Solvates of salts of the compounds provided herein are also provided. Hydrates of the compounds provided herein are also provided.

[0057] Any formula or structure provided herein is also intended to represent both the unlabeled and isotope-labeled forms of the compounds. An isotope-labeled compound has the structure represented by the formula given herein, except that one or more atoms are replaced by atoms having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the compounds of this disclosure include: 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 Isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as I, are included, but are not limited to these. Various isotope-labeled compounds of this disclosure include, for example, 2 H, 3 H, 13 C and 14 These are compounds incorporating radioactive isotopes such as 13C, which are also provided herein. Such isotope-labeled compounds are used in metabolic studies, reaction kinetic studies, and detection methods such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), including drug or substrate tissue distribution assays. It may be useful in technology or imaging techniques, or in radiation therapy for patients.

[0058] This disclosure also includes compounds of formula I, II, or IIa, in which 1 to n hydrogens bonded to a carbon atom are exchanged by deuterium, where n is the number of hydrogens in the molecule. Such compounds exhibit increased resistance to metabolism and are therefore useful in extending the half-life of any compound of formula I, II, or IIa when administered to mammals, particularly 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 employing starting materials in which one or more hydrogens have been exchanged by deuterium.

[0059] The deuterium-labeled or deuterium-substituted therapeutic compounds of this disclosure may have improved DMPK (drug metabolism and pharmacokinetic) properties with respect to absorption, distribution, metabolism, and excretion (ADME). Substitution with heavier isotopes such as deuterium may result in certain therapeutic advantages due to greater metabolic stability, such as extended half-life in vivo, reduced dose requirements, and / or improved therapeutic index. 18 Fluorine-labeled compounds may be useful in PET or SPECT testing. The isotope-labeled compounds and their prodrugs of this disclosure can generally be prepared by substituting readily available isotope-labeling reagents with non-isotope-labeling reagents, by performing the procedures disclosed in the scheme or the examples and preparations described below. In this context, deuterium is understood to be a substituent in the compounds of formula I, II, or IIa.

[0060] The concentration of such heavier isotopes, specifically deuterium, can be defined by the isotopic enrichment factor. In the compounds of this disclosure, any atom not specifically designated as a particular isotope represents 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 the isotopic composition of the natural abundance of hydrogen. Therefore, in the compounds of this disclosure, any atom specifically designated as deuterium (D) represents deuterium.

[0061] In many cases, the compounds of this disclosure can form acidic salts and / or basic salts in the presence of an amino group and / or a carboxyl group or a similar group.

[0062] The term "pharmaceutically acceptable salt" of a given compound is a biological term for the given compound. This refers to salts that retain their scientific efficacy and properties and are not biologically or otherwise undesirable. Pharmaceutically acceptable base addition salts can be prepared from inorganic and organic bases. Salts derived from inorganic bases include, but are not limited to, sodium salts, potassium salts, lithium salts, ammonium salts, calcium salts, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, such as alkylamines, dialkylamines, trialkylamines, substituted alkylamines, di(substituted alkyl)amines, tri(substituted alkyl)amines, alkenylamines, dialkenylamines, trialkenylamines, substituted alkenylamines, di(substituted alkenyl)amines, tri(substituted alkenyl)amines, mono, di or tricycloalkylamines, mono, di or triarylamines, or mixed amines. Specific examples of suitable amines include, but are not limited to, isopropylamine, trimethylamine, diethylamine, tri(iso-propyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, and N-ethylpiperidine.

[0063] Pharmaceutically acceptable acid addition salts can be prepared from inorganic and organic acids. Salts derived from inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Salts derived from organic acids include acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid.

[0064] As used herein, “pharmaceutically acceptable carriers” or “pharmaceutically acceptable excipients” include all kinds of solvents, dispersions, coatings, antimicrobials and antifungals, isotonic agents, and absorption retarders. The use of such media and activators for pharmaceutically active substances is well known in the art. Any conventional media or activator is intended for use in therapeutic compositions, provided that it is not incompatible with the active ingredient. Supplementary active ingredients may also be incorporated into the composition.

[0065] "Treatment" or "treating" is an approach to obtain beneficial or desired outcomes, including clinical outcomes. Beneficial or desired clinical outcomes may include one or more of the following: a) inhibiting the disease or condition (i.e., reducing one or more symptoms resulting from the disease or condition, and / or attenuating the severity of the disease or condition); b) delaying or preventing the onset of one or more clinical symptoms associated with the disease or condition (i.e., 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 (i.e., metastasis)); and / or c) alleviating the disease, i.e., causing regression of clinical symptoms (i.e., improving the disease state, providing partial or complete remission of the disease or condition, enhancing the effects of another drug, slowing the progression of the disease, improving quality of life, and / or prolonging survival).

[0066] "Prevention" or "prevention" means any treatment of a disease or condition that prevents the development of clinical symptoms of the disease or condition. In some embodiments, the compound may be administered to subjects (including humans) who are at risk or have a family history of the disease or condition.

[0067] "Subject" refers to an animal, such as a mammal (including a human), that has been or will be the subject of treatment, observation, or experimentation. The methods described herein may be useful in human therapeutic and / or veterinary applications. In some embodiments, the subject is a mammal. In one embodiment, the subject is a human.

[0068] The terms “therapeutic dose” or “effective dose” for any compound or pharmaceutically acceptable salt, isomer, or mixture thereof described herein mean an amount sufficient to, when administered to a subject, produce a therapeutic effect and provide a therapeutic benefit such as improvement of symptoms or delay of disease progression. For example, a therapeutic dose may be an amount sufficient to reduce the symptoms of a disease or condition in response to the activation of protein kinase C (PKC). The therapeutic dose may vary depending on the subject, the disease or condition being treated, the subject’s weight and age, the severity of the disease or condition, and the mode of administration, and can be easily determined by those skilled in the art. II. Compounds

[0069] In one embodiment, Formula I, [ka] A compound of, During the ceremony, R 2 and R 3 Each of them is independently H or C 1~3 It is alkyl, Each R 5 These are halogens that may be the same or different, R 1 H, -CN, halogen, C 1~8 Alkyl, C 3~7 Monocyclic cycloalkyl, -C(O)NR 6 R 6 , -NR 6 R 6 , -NR 7 C(O)R 8 , or -C(O)R 8 And at this time, C 1~8 Alkyl and C3~7 Monocyclic cycloalkyl groups are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. Ring B, together with the two carbon atoms to which it is bonded, C 3~7 Forming monocyclic cycloalkyls, 5-9 member condensed or cross-linked bicyclic cycloalkyls, 3-4 member monocyclic heterocyclines, 5-7 member monocyclic heterocyclines, or 5-9 member condensed or cross-linked bicyclic heterocyclines, At this time, C 3~7 Monocyclic cycloalkyls, 5-9 membered condensed or cross-linked bicyclic cycloalkyls, 3-7 membered monocyclic heterocyclils, and 5-9 membered condensed or cross-linked bicyclic heterocyclils each have 1-5 R 16 It is optionally substituted in the base, In this case, the 3-4 membered monocyclic heterocyclil has 1-2 ring heteroatoms independently selected from N, O, and S. In this case, the 5-7 member monocyclic heterocyclil and the 5-9 member condensed or bridging bicyclic heterocyclil each have 1-3 ring heteroatoms independently selected from N, O, and S. Each R 16 These are independently oxo, -OH, halogen, -CN, and C. 1~8 Alkyl, C 1~4 Alkoxy, C 3~7 Monocyclic cycloalkyl, -C(O)NR 6 R 6 , -NR 6 R 6 , -NR 6 C(O)R 8 , or -C(O)R 8 And at this time, C 1~8 Alkyl and C 3~7 Monocyclic cycloalkyl groups are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. R 4 These include phenyl, 5-6 membered monocyclic heterocyclyl, and 5-6 membered monocyclic heteroaryl. These are 8-10 member condensed or cross-linked bicyclic heterocyclines, 8-10 member condensed bicyclic heteroaryls, 9-12 member condensed or cross-linked tricyclic heterocyclines, or 9-12 member condensed tricyclic heteroaryls. In this case, phenyl, 5-6 member monocyclic heterocyclil, 5-6 member monocyclic heteroaryl, 8-10 member condensed or cross-linked bicyclic heterocyclil, 8-10 member condensed bicyclic heteroaryl, 9-12 member condensed or cross-linked tricyclic heterocyclil, and 9-12 member condensed tricyclic heteroaryl each have 1-3 R 4a It is optionally substituted in the base, In this case, each of the 5-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, 9-12 member condensed or bridged tricyclic heterocyclils, and 9-12 member condensed tricyclic heteroaryls each has 1-3 ring heteroatoms independently selected from N, O, and S. Each R 4a These are independently oxo, -OH, halogen, -CN, and C. 1~8 Alkyl, C 1~8 Alkoxy, -NR 6 R 6 , -NR 7 S(O)2R 9 , -NR 7 S(O)2NR 6 R 6 , -NR 7 C(O)R 8 , -NR 7 C(O)R 10 NR 6 R 6 , -NR 7 C(O)NR 6 R 6 , or -C(O)NR 6 R 6 And at this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy, or 1 to 3 R's 4a Two of the R groups 4a It is bonded to the same carbon, and has two R4a Together with the carbon atoms to which they are bonded, C 3~7 Forms a monocyclic cycloalkyl structure, Each R 6 H and C are independent of each other. 1~8 Alkyl, C 3~7 A monocyclic cycloalkyl, or a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, At this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls and 4-6 membered monocyclic heterocyclils having 1-3 ring heteroatoms independently selected from N, O, and S are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy, or Both R 6 Together with the nitrogen atoms to which they are bonded, they form a 4-6 member monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S. Each R 7 Independently, H or C, which may be the same or different. 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. Each R 8 These are independently -OH, C 1~8 Alkyl, C 1~8 Alkoxy, C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 4-6 membered monocyclic heteroaryl. At this time, C 1~8 Alkyl and C 1~8 Alkoxy compounds are, respectively, -OH, halogen, -CN, and C. 1~4It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 4-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, the 4-6 membered monocyclic heterocyclyl and the 4-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S. Each R 9 Independently, C 1~8 Alkyl, C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. At this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 membered monocyclic heterocyclyls and 5-6 membered monocyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S. Each R 10 C may be the same or different. 1~4 It is alkylene, Ring A, together with the two carbon atoms to which it is bonded, forms a 5-6 member monocyclic heterocyclil or a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heterocyclil and the 5-6 member monocyclic heteroaryl are each substituted with one Z group and each has 1-3 ring heteroatoms independently selected from N, O, and S. Z is i) Oxo, ii)-OH, iii)-CN, iv)C 1~5 It is an alkyl group, and in this case, C 1~5 Alkyl groups consist of -OH and C 1~4 It is substituted with one group selected from alkoxy, in which case C 1~5 The alkyl group is further optionally substituted with one or two groups independently selected from -OH, halogen, and -CN. 1~5 Alkyl, v)C 6~8 It is an alkyl group, and in this case, C 6~8 Alkyls include -OH, halogens, -CN, and C 1~4 C is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 6~8 Alkyl, vi)-Z 1 -Z 2 -Z 3 -Z 4 And, At this time, 1 C 2~6 It is an alkynylene, -OH, halogen, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, 2 and Z 3 Each of them is independent of C 3~7 Monocyclic cycloalkylene, C 6~10 The compound is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, a 5-6 member monocyclic heteroarylene, an 8-10 member condensed or cross-linked bicyclic heterocyclylene, an 8-10 member condensed bicyclic heteroarylene, or a 7-10 member spirocyclic heterocyclylene, in which case C 3~7 Monocyclic cycloalkylene, C 6~10Monocyclic or condensed bicyclic arylenes, 4-6 member monocyclic heterocyclylenes, 5-6 member monocyclic heteroarylenes, 8-10 member condensed or cross-linked bicyclic heterocyclylenes, 8-10 member condensed bicyclic heteroarylenes, and 7-10 member spirocyclic heterocyclylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from, in which case 4-6 membered monocyclic heterocyclenes, 5-6 membered monocyclic heteroarylenes, 8-10 membered condensed or bridged bicyclic heterocyclenes, 8-10 membered condensed bicyclic heteroarylenes, and 7-10 membered spirocyclic heterocyclenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S. At this time, 4 C 3~7 Monocyclic cycloalkyl, C 6~10 The compound is a monocyclic or condensed bicyclic aryl, a 4-6 member monocyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed or bridged bicyclic heterocyclil, an 8-10 member condensed bicyclic heteroaryl, or a 7-10 member spirocyclic heterocyclil, in which case C 3~7 Monocyclic cycloalkyl, C 6~10 Monocyclic or condensed bicyclic aryls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridged bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclines are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from the above, in which case 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils. Each of these has 1 to 3 ring heteroatoms, independently selected from N, O, and S, and -Z 1 -Z 2 -Z 3 -Z4 , vii)C 3~7 Monocyclic cycloalkyl, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 C is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 3~7 Monocyclic cycloalkyl, viii)-S(C 1~8 Alkyl) and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 -S(C) is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 1~8 Alkyl), ix)-NR 11 R 12 And at this time, R 11 and R 12 One of them is H or C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 Alkyl, C 3~7 These are monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, or 7-10 membered spirocyclic heterocyclines. In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base, At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S, -NR 11 R 12 , x)C 6~10 Monocyclic or condensed bicyclic aryls, comprising -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , -NR 6 R 6 They are optionally substituted with 1 to 3 groups, independently selected from 4-6 membered monocyclic heterocyclines and 5-6 membered monocyclic heteroaryls. In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , and -NR 6 R 6 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, 4-6 membered monocyclic heterocyclyls and 5-6 membered monocyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S, and C 6~10 Monocyclic or fused bicyclic aryl, xi) A 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 A 4-6 member monocyclic heterocycline that is optionally substituted at the base. xii) 8-10 membered condensed or bridging bicyclic heterocyclines having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 138-10 member condensed or cross-linked bicyclic heterocyclines, which are optionally substituted at the base. xiii) A 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 A 5-6 member monocyclic heteroaryl compound that is optionally substituted at the base. xiv) 8-10 membered condensed bicyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 An 8-10 member condensed bicyclic heteroaryl, or, which is optionally substituted at the base. xv) A 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 It is a 7-10 membered spirocyclic heterocycline that is optionally substituted at the base, Each R 17 These are independently -OH, halogen, -CN, and C 1~4 Alkoxy, -NR 6 R 6 , C 3~7 These include monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclines. At this time, C 1~4 Alkoxy, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S. Each R 13 These are independently oxo, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -NR 6 R 6 , -C(O)R 10 NR 6 R 6 -C(O)NR 6 R 6 , -C(O)R 8 , C 6~10 These are monocyclic or condensed bicyclic aryls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridged bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, or 7-10 membered spirocyclic heterocyclines. At this time, C 6~10 Monocyclic or condensed bicyclic aryls, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 R 14 It is optionally substituted in the base, In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S. Each R 14 These are, independently, halogen, C 1~4 Alkyl, -C(O)R 8 These are 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, or 7-10 member spirocyclic heterocyclils. At this time, C1~4 Alkyls include -OH, halogens, CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils are each C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted, In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S. Each R 15 C can be independent and may be the same or different. 1~3 It is alkyl, n is a compound or a pharmaceutically acceptable salt thereof, where n is 0, 1, 2, or 3.

[0070] In some embodiments, the compound of formula I is the compound of formula Ia, [ka] or a pharmaceutically acceptable salt thereof.

[0071] In some embodiments of compounds of formula I or Ia, or pharmaceutically acceptable salts thereof, R 2 and R 3 Each of them is independently H or C 1~3 It is alkyl, Each R 5 These are halogens that may be the same or different, R 1 H, -CN, halogen, C 1~8Alkyl, or C 3~7 It is a monocyclic cycloalkyl, and in this case, C 1~8 Alkyl and C 3~7 Monocyclic cycloalkyl groups are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. Ring B, together with the two carbon atoms to which it is bonded, C 3~7 Forming monocyclic cycloalkyl or 5-9 member condensation or crosslinked bicyclic cycloalkyl, At this time, C 3~7 Monocyclic cycloalkyls and 5-9 member condensed or cross-linked bicyclic cycloalkyls each have 1-5 R groups. 16a It is optionally substituted in the base, Each R 16a These are independently -OH, halogen, -CN, and C 1~8 Alkyl, C 1~4 Alkoxy, and C 3~7 It is a monocyclic cycloalkyl, and in this case, C 1~8 Alkyl and C 3~7 Monocyclic cycloalkyl groups are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. R 4 These are phenyl, 8-10 member condensed or cross-linked bicyclic heterocyclyl, 8-10 member condensed bicyclic heteroaryl, or 9-12 member condensed or cross-linked tricyclic heterocyclyl. In this case, phenyl, 8-10 member condensed or cross-linked bicyclic heterocyclyl, 8-10 member condensed bicyclic heteroaryl, and 9-12 member condensed or cross-linked tricyclic heterocyclyl each have 1-3 R 4a It is optionally substituted in the base, In this case, each of the 8-10 member condensed or bridged bicyclic heterocyclyls, 8-10 member condensed bicyclic heteroaryls, and 9-12 member condensed or bridged tricyclic heterocyclyls has 1-3 ring heteroatoms independently selected from N, O, and S. Each R 4a These are independently oxo, -OH, halogen, -CN, and C. 1~8Alkyl, C 1~8 Alkoxy, -NR 6 R 6 , -NR 7 S(O)2R 9 , or -C(O)NR 6 R 6 And at this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. 1 to 3 R's 4a Two of the R groups 4a It is bonded to the same carbon, and has two R 4a Together with the carbon atoms to which they are bonded, C 3~7 Forms a monocyclic cycloalkyl structure, Each R 6 H and C are independent of each other. 1~8 Alkyl, or C 3~7 It is a monocyclic cycloalkyl, At this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 Selected independently of the alkoxy, with 1 to 3 groups arbitrarily chosen. It has been replaced, Each R 7 Independently, H or C, which may be the same or different. 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. Each R 8 These are independently -OH, C 1~8 Alkyl, or C 1~8 It is an alkoxy, Each R 9 Independently, C 1~8 Alkyl or C3~7 It is a monocyclic cycloalkyl, At this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. Each R 10 C may be the same or different. 1~4 It is alkylene, Ring A, together with the two carbon atoms to which it is bonded, forms a 5-6 member monocyclic heterocyclil or a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heterocyclil and the 5-6 member monocyclic heteroaryl are each substituted with one Z group and each has 1-3 ring heteroatoms independently selected from N, O, and S. Z is i) Oxo, ii)-OH, iii)-CN, iv)C 1~5 It is an alkyl group, and in this case, C 1~5 Alkyl groups consist of -OH and C 1~4 It is substituted with one group selected from alkoxy, in which case C 1~5 The alkyl group is further optionally substituted with one or two groups independently selected from -OH, halogen, and -CN. 1~5 Alkyl, v)C 6~8 It is an alkyl group, and in this case, C 6~8 Alkyls include -OH, halogens, -CN, and C 1~4 C is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 6~8 Alkyl, vi)-Z 1 -Z 2 -Z 3 -Z 4And, At this time, 1 C 2~6 It is an alkynylene, -OH, halogen, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, 2 C 6~10 It is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, or a 5-6 member monocyclic heteroarylene, in which case C 6~10 Monocyclic or condensed bicyclic arylenes, 4-6 membered monocyclic heterocyclylenes, and 5-6 membered monocyclic heteroarylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from, in which case the 4-6 membered monocyclic heterocyclenes and 5-6 membered monocyclic heteroarylenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S. At this time, 3 These are 5-6 member monocyclic heterocyclylenes or 5-6 member monocyclic heteroarylenes. In this case, the 5-6 member monocyclic heterocyclylene and the 5-6 member monocyclic heteroarylene are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 5-6 member monocyclic heterocyclene and the 5-6 member monocyclic heteroarylene each have 1-3 ring heteroatoms independently selected from N, O, and S. At this time, 4 These are 5-6 membered monocyclic heterocyclyls or 5-6 membered monocyclic heteroaryls. In this case, 5-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O) R8 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 5-6 membered monocyclic heterocyclyl and 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S. vii)C 3~7 Monocyclic cycloalkyl, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 -Z is optionally substituted with 1 to 3 groups, independently selected from the alkoxy group. 1 -Z 2 -Z 3 -Z 4 , viii)-S(C 1~4 Alkyl) and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 -S(C) is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 1~4 Alkyl), ix)-NR 11 R 12 And at this time, R 11 and R 12 One of them is H or C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 Alkyl, C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17a It is substituted with the base, At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 5-6 membered monocyclic heteroaryls are classified as oxo, -OH, halogen, -CN, and C, respectively. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S, -NR 11 R 12 , x)C 6~10 Monocyclic or condensed bicyclic aryls, comprising -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , -NR 6 R 6 They are optionally substituted with 1 to 3 groups, independently selected from 4-6 membered monocyclic heterocyclines and 5-6 membered monocyclic heteroaryls. In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , and -NR 6 R 6 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, 4-6 membered monocyclic heterocyclyls and 5-6 membered monocyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S, and C 6~10 Monocyclic or fused bicyclic aryl, xi) A 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 A 4-6 member monocyclic heterocycline that is optionally substituted at the base. xii) 8-10 membered condensed or bridging bicyclic heterocyclines having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 8-10 member condensed or cross-linked bicyclic heterocyclines, which are optionally substituted at the base. xiii) A 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 A 5-6 member monocyclic heteroaryl compound that is optionally substituted at the base. xiv) 8-10 member condensed bicyclic heteroaryls, with 1-3 R 13 An 8-10 member condensed bicyclic heteroaryl, or, which is optionally substituted at the base. xv) A 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 It is a 7-10 membered spirocyclic heterocycline that is optionally substituted at the base, Each R 17a These are independently -OH, halogen, -CN, and C 1~4 Alkoxy, -NR 6 R 6 , C 3~7 These are monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, and 5-6 membered monocyclic heteroaryls. At this time, C 1~4 Alkoxy, C 3~7 Monocyclic cycloalkyl, 4-6 member monocyclic heteroalkyl Rosicrill and 5-6 membered monocyclic heteroaryls are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 membered monocyclic heterocyclyls and 5-6 membered monocyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S. Each R 13 These are independently oxo, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -NR 6 R 6 , -C(O)R 10 NR 6 R 6 -C(O)NR 6 R 6 , -C(O)R8 , C 6~10 These are monocyclic or condensed bicyclic aryls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridged bicyclic heterocyclines, or 8-10 membered condensed bicyclic heteroaryls. At this time, C 6~10 Monocyclic or condensed bicyclic aryls, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, and 8-10 member condensed bicyclic heteroaryls each have 1-3 R 14 It is optionally substituted in the base, In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, and 8-10 member condensed bicyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S. Each R 14 These are, independently, halogen, C 1~4 Alkyl, -C(O)R 8 , or a 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S, At this time, C 1~4 Alkyls include -OH, halogens, CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, a 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms, independently selected from N, O, and S, is C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted, Each R 15 C can be independent and may be the same or different. 1~3 It is alkyl, n is 0, 1, 2, or 3.

[0072] In some embodiments of the compound of formula I or Ia, or a pharmaceutically acceptable salt thereof, n is 0, 1, 2, or 3. In some embodiments of the compound of formula I or Ia, or a pharmaceutically acceptable salt thereof, n is 0. In some embodiments of the compound of formula I or Ia, or a pharmaceutically acceptable salt thereof, n is 1. In some embodiments of the compound of formula I or Ia, or a pharmaceutically acceptable salt thereof, n is 2. In some embodiments of the compound of formula I or Ia, or a pharmaceutically acceptable salt thereof, n is 3.

[0073] In some embodiments, the compound of formula I is the compound of formula II, [ka] or a pharmaceutically acceptable salt thereof.

[0074] In some embodiments, the compound of formula I, Ia, or II is the compound of formula IIa, [ka] or a pharmaceutically acceptable salt thereof.

[0075] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 2 and R 3 Each of them is independently H or C 1~3 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 2 and R 3 One of them is H, and R 2 and R 3 Of these, the other is C 1~3 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 2 and R 3 One of them is H, and R 2 and R 3The other of these is methyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 2 and R 3 One of them is H, and R 2 and R 3 The other of these is ethyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 2 and R 3 One of them is H, and R 2 and R 3 The other of these is propyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 2 and R 3 One of them is H, and R 2 and R 3 The other of these is isopropyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, both R 2 and R 3 is H. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 2 and R 3 These are, independently, methyl, ethyl, propyl, or isopropyl.

[0076] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 5 R is a halogen which may be the same or different. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, each R 5 R is independently chloro, fluoro, bromo, or iodine. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, each R 5 These are independently chloro, fluoro, or bromo. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 5is fluoro. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, two R 5 is fluoro. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 5 It is fluoro.

[0077] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, C 3~7 Monocyclic cycloalkyl, 5-9 member condensed or cross-linked bicyclic cycloalkyl, 3-4 member monocyclic heterocyclyl, 5-7 member monocyclic heterocyclyl, or 5-9 member condensed or cross-linked bicyclic heterocyclyl Forming cyclils, At this time, C 3~7 Monocyclic cycloalkyls, 5-9 membered condensed or cross-linked bicyclic cycloalkyls, 3-7 membered monocyclic heterocyclils, and 5-9 membered condensed or cross-linked bicyclic heterocyclils each have 1-5 R 16 It is optionally substituted in the base, In this case, the 3-4 membered monocyclic heterocyclil has 1-2 ring heteroatoms independently selected from N, O, and S. In this case, the 5-7 member monocyclic heterocyclil and the 5-9 member condensed or bridging bicyclic heterocyclil each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0078] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, C 3~7 Forming monocyclic cycloalkyl or 5-9 member condensation or crosslinked bicyclic cycloalkyl, At this time, C 3~7 Monocyclic cycloalkyls and 5-9 member condensed or cross-linked bicyclic cycloalkyls each have 1-5 R groups. 16a It is optionally substituted in the base.

[0079] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which it is bonded, forms a cyclohexyl or a 6-7 membered condensed or cross-linked bicyclic cycloalkyl group, where the cyclohexyl and the 6-7 membered condensed or cross-linked bicyclic cycloalkyl groups are each optionally substituted with 1 to 5 halogens.

[0080] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, C 3~7 It forms a monocyclic cycloalkyl, and at this time, C 3~7 Monocyclic cycloalkyl groups have 1 to 5 R groups. 16 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, is C 3~7 It forms a monocyclic cycloalkyl, and at this time, C 3~7 Monocyclic cycloalkyl groups have 1 to 5 R groups. 16a It is optionally substituted in the base.

[0081] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, C 3~7 It forms a monocyclic cycloalkyl, and at this time, C 3~7 Monocyclic cycloalkyl groups have 1 to 5 R groups. 16 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, is C 3~7 It forms a monocyclic cycloalkyl, and at this time, C 3~7 Monocyclic cycloalkyl groups have 1 to 5 R groups. 16a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, is C3~7 It forms a monocyclic cycloalkyl, and at this time, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C 1~8 Substituted with 1 to 5 groups independently selected from alkyl groups. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, is C 3~7 It forms a monocyclic cycloalkyl, and at this time, C 3~7 Monocyclic cycloalkyl groups are substituted with 1 to 5 halogens. In some embodiments of compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which they are bonded, is C 3~7 It forms a monocyclic cycloalkyl, and at this time, C 3~7 Monocyclic cycloalkyl groups are substituted with 1 to 5 fluorocarbons. In some embodiments of compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a cyclopentyl, in which case the cyclopentyl is It is substituted with 1 to 5 fluorocarbons.

[0082] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, C 3~7 They form a monocyclic cycloalkyl group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbon atoms to which they are bonded, forms a cyclopentyl or cyclohexyl group.

[0083] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbon atoms to which it is bonded, forms a cyclohexyl molecule, in which case the cyclohexyl molecule is optionally substituted with 1 to 5 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbon atoms to which it is bonded, forms a cyclohexyl molecule, in which case the cyclohexyl molecule is optionally substituted with 1 to 5 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbon atoms to which it is bonded, forms a cyclohexyl molecule, in which case the cyclohexyl molecule is optionally substituted with 1 to 4 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which it is bonded, forms a cyclohexyl, in which the cyclohexyl is substituted with 1 to 5 fluorocarbons.

[0084] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which it is bonded, forms a 5-9 membered condensation or a bridging bicyclic cycloalkyl group, in which case the 5-9 membered condensation or bridging bicyclic cycloalkyl group has 1-5 R 16 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-9 membered condensation or a bridging bicyclic cycloalkyl group, in which case the 5-9 membered condensation or bridging bicyclic cycloalkyl group has 1-5 R 16a It is optionally substituted in the base.

[0085] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which it is bonded, forms a 5- to 9-membered condensation or a bridging bicyclic cycloalkyl group, in which the 5- to 9-membered condensation or bridging bicyclic cycloalkyl group comprises -OH, halogen, -CN, and C 1~8 It is substituted with 1 to 5 groups independently selected from alkyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a 5- to 9-membered condensate or a bridging bicyclic cycloalkyl group, in which case the 5- to 9-membered condensate or bridging bicyclic cycloalkyl group is substituted with 1 to 5 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a 5- to 9-membered condensate or a bridging bicyclic cycloalkyl group, in which case the 5- to 9-membered condensate or bridging bicyclic cycloalkyl group is substituted with 1 to 4 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a 5- to 9-membered condensation or a bridging bicyclic cycloalkyl group, in which case the 5- to 9-membered condensation or bridging bicyclic cycloalkyl group is substituted with 1 to 5 fluorocarbons. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a 6- to 8-membered condensation or a bridging bicyclic cycloalkyl group, in which case the 6- to 8-membered condensation or bridging bicyclic cycloalkyl group is substituted with 1 to 5 fluorocarbons. Formula I In some embodiments of the compounds of formula Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a six-membered condensate or a cross-linked bicyclic cycloalkyl group, in which case the six-membered condensate or cross-linked bicyclic cycloalkyl group is substituted with 1 to 5 fluorocarbons. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a seven-membered condensate or a cross-linked bicyclic cycloalkyl group, in which case the seven-membered condensate or cross-linked bicyclic cycloalkyl group is substituted with 1 to 5 fluorocarbons.

[0086] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a 6-7 membered condensation or a bridging bicyclic cycloalkyl group, where the 6-7 membered condensation or bridging bicyclic cycloalkyl group is optionally substituted with 1 to 5 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a 6-7 membered condensation or a bridging bicyclic cycloalkyl group, in which case the 6-7 membered condensation or bridging bicyclic cycloalkyl group is substituted with 1 to 4 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B, together with the two carbons to which it is bonded, forms a 6-7 membered condensation or a bridging bicyclic cycloalkyl group, in which case the 6-7 membered condensation or bridging bicyclic cycloalkyl group is substituted with 1 to 3 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which it is bonded, forms a 6-7 membered condensation or a bridging bicyclic cycloalkyl group, in which the 6-7 membered condensation or bridging bicyclic cycloalkyl group is substituted with 1-3 fluorocarbons.

[0087] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 3-4 membered monocyclic heterocycline, in which the 3-4 membered monocyclic heterocycline has 1-2 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 3-4 membered monocyclic heterocycline, in which the 3-4 membered monocyclic heterocycline has 1-2 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16a It is optionally substituted in the base.

[0088] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 3-4 membered monocyclic heterocycline, in which the 3-4 membered monocyclic heterocycline has 1-2 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 3-4 membered monocyclic heterocycline, in which the 3-4 membered monocyclic heterocycline has 1-2 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 3-4 membered monocyclic heterocyclil having 1-2 ring heteroatoms independently selected from N, O, and S.

[0089] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-7 membered monocyclic heterocycline, where the 5-7 membered monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-7 membered monocyclic heterocycline, in which the 5-7 membered monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16a It is optionally substituted in the base.

[0090] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-7 membered monocyclic heterocycline, where the 5-7 membered monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-7 membered monocyclic heterocycline, in which the 5-7 membered monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-7 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0091] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-9 membered condensation or bridging bicyclic heterocycline, where the 5-9 membered condensation or bridging bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-9 membered condensation or bridging bicyclic heterocycline, in which the 5-9 membered condensation or bridging bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16a It is optionally substituted in the base.

[0092] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-9 membered condensation or bridging bicyclic heterocycline, where the 5-9 membered condensation or bridging bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-9 membered condensation or bridging bicyclic heterocycline, in which the 5-9 membered condensation or bridging bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-5 R 16a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B, together with the two carbons to which they are bonded, forms a 5-9 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0093] Compounds of formula I, Ia, II, or IIa, or any of their pharmaceutically acceptable salts. In that embodiment, ring B is cyclohexyl, tetrahydropyranyl, [ka] And, Each of these is oxo, -OH, halogen, -CN, C 1~8 Alkyl, C 1~4 Alkoxy, C 3~7 Monocyclic cycloalkyl, -C(O)NR 6 R 6 , -NR 6 R 6 , -NR 6 C(O)R 8 , and -C(O)R 8 It is arbitrarily substituted by 1 to 5 elements, which are selected independently of each other.

[0094] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B is cyclohexyl, tetrahydropyranyl, [ka] And, Each of these is oxo, -OH, halogen, -CN, C 1~8 Alkyl, C 1~4 Alkoxy, C 3~7 Monocyclic cycloalkyl, -C(O)NR 6 R 6 , -NR 6 R 6 , -NR 6 C(O)R 8 , and -C(O)R 8 It is arbitrarily substituted by 1 to 4 groups, which are selected independently of each other.

[0095] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring B is cyclohexyl, [ka] And, Each of these is optionally substituted with 1 to 5 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, ring B is cyclohexyl, [ka] And, Each of these is optionally substituted with 1 to 5 fluorocarbons.

[0096] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 16 These are independently oxo, -OH, halogen, -CN, and C. 1~ 8 alkyl, C 1~4 Alkoxy, C 3~7 Monocyclic cycloalkyl, -C(O)NR 6 R 6 , -NR 6 R 6 , -NR 6 C(O)R 8 , or -C(O)R 8 And at this time, C 1~8 Alkyl and C 3~7 Monocyclic cycloalkyl groups are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy group.

[0097] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 16a These are independently -OH, halogen, -CN, and C 1~8 Alkyl, C 1~4 Alkoxy, and C 3~7 It is a monocyclic cycloalkyl, and in this case, C 1~8 Alkyl and C 3~7 Monocyclic cycloalkyl groups are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy group.

[0098] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, [ka] teeth, [ka] [ka] That is the case.

[0099] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, [ka] teeth, [ka] That is the case.

[0100] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 H, -CN, halogen, C 1~8 Alkyl, C 3~7 Monocyclic cycloalkyl, -C(O)NR 6 R 6 , -NR 6 R 6 , -NR 7 C(O)R 8 , or -C(O)R 8 And at this time, C 1~8 Alkyl and C 3~7 Monocyclic cycloalkyl groups are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 H, -CN, halogen, C 1~8 Alkyl, or C 3~7 It is a monocyclic cycloalkyl, and in this case, C 1~8Alkyl and C 3~7 Monocyclic cycloalkyl groups are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy group.

[0101] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 is H. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 It is -CN.

[0102] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 is a halogen. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 is chloro, fluoro, bromo, or iodine. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 These are chloro, fluoro, or bromo.

[0103] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 1~6 It is alkyl, and in this case, C 1~6 Alkyls include -OH, halogens, -CN, and C 1~4The compounds are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, , R 1 C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 1~4 It is alkyl, and in this case, C 1~4 The alkyl group is optionally substituted with 1 to 3 halogens.

[0104] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 1~6 It is alkyl, and in this case, C 1~6 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 1~4It is alkyl, and in this case, C 1~4 The alkyl group is substituted with 1 to 3 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 1~3 It is alkyl, and in this case, C 1~3 The alkyl group is substituted with 1 to 3 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 1~3 It is alkyl, and in this case, C 1~3 The alkyl group is substituted with 1 to 3 fluorocarbons. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 is a methyl compound substituted with 1 to 3 fluorocarbons. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 R is ethyl substituted with 1 to 3 fluorocarbons. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 This is either -CHF2 or -CF3.

[0105] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 C 1~8 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 C 1~6 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 C 1~4 It is alkyl.

[0106] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 C 3~7 It is a monocyclic cycloalkyl, and in this case, C3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 C 3~7 It is a monocyclic cycloalkyl compound.

[0107] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 1 is -C(O)NR 6 R 6 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 teeth,- NR 6 R 6 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 -NR 7 C(O)R 8 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 1 is -C(O)R 8 That is the case.

[0108] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4These are phenyl, a 5-6 member monocyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed or cross-linked bicyclic heterocyclil, an 8-10 member condensed bicyclic heteroaryl, a 9-12 member condensed or cross-linked tricyclic heterocyclil, or a 9-12 member condensed tricyclic heteroaryl. In this case, phenyl, 5-6 member monocyclic heterocyclil, 5-6 member monocyclic heteroaryl, 8-10 member condensed or cross-linked bicyclic heterocyclil, 8-10 member condensed bicyclic heteroaryl, 9-12 member condensed or cross-linked tricyclic heterocyclil, and 9-12 member condensed tricyclic heteroaryl each have 1-3 R 4a It is optionally substituted in the base, In this case, each of the 5-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, 9-12 member condensed or bridged tricyclic heterocyclils, and 9-12 member condensed tricyclic heteroaryls each has 1-3 ring heteroatoms independently selected from N, O, and S.

[0109] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 These are phenyl, 8-10 member condensed or cross-linked bicyclic heterocyclyl, 8-10 member condensed bicyclic heteroaryl, or 9-12 member condensed or cross-linked tricyclic heterocyclyl. In this case, phenyl, 8-10 member condensed or cross-linked bicyclic heterocyclyl, 8-10 member condensed bicyclic heteroaryl, and 9-12 member condensed or cross-linked tricyclic heterocyclyl each have 1-3 R 4a It is optionally substituted in the base, In this case, the 8-10 member condensed or bridged bicyclic heterocyclil, the 8-10 member condensed bicyclic heteroaryl, and the 9-12 member condensed or bridged tricyclic heterocyclil each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0110] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4is phenyl or a 9-10 member condensed or cross-linked bicyclic heterocycline, in which case phenyl and the 9-10 member condensed or cross-linked bicyclic heterocycline each have 1-3 R 4a The group is optionally substituted, and in this case, the 9-10 membered condensed or bridging bicyclic heterocyclil has 1-3 ring heteroatoms independently selected from N, O, and S.

[0111] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 It is phenyl, and in this case, phenyl has 1 to 3 R 4a The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 It is phenyl, and in this case, phenyl has 1 to 3 R 4a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 It is phenyl.

[0112] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 It is a 5-6 member monocyclic heterocycline, in which the 5-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 It is a 5-6 member monocyclic heterocycline, in which the 5-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4is a 5- to 6-membered monocyclic heterocyclyl having 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0113] In some embodiments of the compound of formula I, Ia, II, or IIa, or a pharmaceutically acceptable salt thereof, R 4 is a 5- to 6-membered monocyclic heteroaryl, wherein the 5- to 6-membered monocyclic heteroaryl has 1 to 3 ring heteroatoms independently selected from N, O, and S, and is optionally substituted with 1 to 3 R 4a groups. In some embodiments of the compound of formula I, Ia, II, or IIa, or a pharmaceutically acceptable salt thereof, R 4 is a 5- to 6-membered monocyclic heteroaryl, wherein the 5- to 6-membered monocyclic heteroaryl has 1 to 3 ring heteroatoms independently selected from N, O, and S, and is substituted with 1 to 3 R 4a groups. In some embodiments of the compound of formula I, Ia, II, or IIa, or a pharmaceutically acceptable salt thereof, R 4 is a 5- to 6-membered monocyclic heteroaryl having 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0114] In some embodiments of the compound of formula I, Ia, II, or IIa, or a pharmaceutically acceptable salt thereof, R 4 is an 8- to 10-membered fused or bridged bicyclic heterocyclyl, wherein the 8- to 10-membered fused or bridged bicyclic heterocyclyl has 1 to 3 ring heteroatoms independently selected from N, O, and S, and is optionally substituted with 1 to 3 R 4a groups. In some embodiments of the compound of formula I, Ia, II, or IIa, or a pharmaceutically acceptable salt thereof, R 4 is an 8- to 10-membered fused or bridged bicyclic heterocyclyl, wherein the 8- to 10-membered fused or bridged bicyclic heterocyclyl has 1 to 3 ring heteroatoms independently selected from N, O, and S, and is substituted with 1 to 3 R 4aIt is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 It is an 8-10 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0115] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 This is a 9-10 member condensed or bridged bicyclic heterocycline, in which the 9-10 member condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 This is a 9-10 member condensed or bridged bicyclic heterocycline, in which the 9-10 member condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 It is a 9-10 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0116] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 This is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4This is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 N, O The 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms, which are independently selected from and S.

[0117] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 It is a 9-12 member condensed or bridged tricyclic heterocycline, in which the 9-12 member condensed or bridged tricyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 It is a 9-12 member condensed or bridged tricyclic heterocycline, in which the 9-12 member condensed or bridged tricyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 It is a 9-12 membered condensed or bridging tricyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0118] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 This is a 9-12 membered condensed tricyclic heteroaryl, in which the 9-12 membered condensed tricyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4aThe group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 This is a 9-12 membered condensed tricyclic heteroaryl, in which the 9-12 membered condensed tricyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 4a It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 4 It is a 9-12 membered condensed tricyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0119] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 teeth, [ka] And, Each of these has 1 to 3 R's. 4a It is optionally substituted in the base.

[0120] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 teeth, [ka] And, Each of these has 1 to 3 R's. 4a It is substituted with the base.

[0121] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 teeth, [ka] And, Each of these has 1 to 3 R's. 4a It is optionally substituted in the base.

[0122] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 teeth, [ka] And, Each of these has 1 to 3 R's. 4a It is substituted with the base.

[0123] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 teeth, [ka] And, 1 to 3 R's 4a It is optionally substituted in the base.

[0124] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 teeth, [ka] And, 1 to 3 R's 4a It is substituted with the base.

[0125] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 4a These are independently oxo, -OH, halogen, -CN, and C. 1~8 Alkyl, C 1~8 Alkoxy, -NR 6 R 6 , -NR 7 S(O)2R 9 , -NR 7S(O)2NR 6 R 6 、 -NR 7 C(O)R 8 、 -NR 7 C(O)R 10 NR 6 R 6 、 -NR 7 C(O)NR 6 R 6 、 or -C(O)NR 6 R 6 wherein, C 1~8 alkyl is optionally substituted with 1 to 3 groups independently selected from -OH, halogen, -CN, and C 1~4 alkoxy, or two of the 1 to 3 R 4a groups are bonded to the same carbon, and the two R 4a form, together with the carbon to which they are bonded, a C 4a monocyclic cycloalkyl. In some embodiments of the compounds of Formula I, Ia, II, or IIa, or a pharmaceutically acceptable salt thereof, each R 3~7 is independently oxo, -OH, halogen, -CN, C 4a alkyl, C 1~8 alkoxy, -NR 1~8 R 6 R 6 、 -NR 7 S(O)2R 9 、 or -C(O)NR 6 R 6 wherein, C 1~8 alkyl is optionally substituted with 1 to 3 groups independently selected from -OH, halogen, -CN, and C 1~4 alkoxy, or two of the 1 to 3 R 4a groups are bonded to the same carbon, and the two R 4a form, together with the carbon to which they are bonded, a C 4a monocyclic cycloalkyl. 3~7 In some embodiments of the compounds of Formula I, Ia, II, or IIa, or a pharmaceutically acceptable salt thereof, each R

[0126] 式I、Ia、II、若しくはIIaの化合物、又はその薬学的に許容される塩のいくつかの実施形態では、各R 4aThese are independently oxo, -OH, halogen, -CN, and C. 1~8 Alkyl, C 1~8 Alkoxy, -NR 6 R 6 , -NR 7 S(O)2R 9 , -NR 7 S(O)2NR 6 R 6 , -NR 7 C(O)R 8 , -NR 7 C(O)R 10 NR 6 R 6 , -NR 7 C(O)NR 6 R 6 , or -C(O)NR 6 R 6 And at this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, each R 4a These are independently oxo, -OH, halogen, -CN, and C. 1~8 Alkyl, C 1~8 Alkoxy, -NR 6 R 6 , -NR 7 S(O)2R 9 , or -C(O)NR 6 R 6 And at this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy group.

[0127] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 4a These are independently oxo, halogen, -CN, and C 1~8 Alkyl, -NR 6 R 6 , -NR 7 S(O)2R 9, or -C(O)NR 6 R 6 That is the case.

[0128] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a is an oxo. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 4a It is an oxo. Compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable In some embodiments of the salt, one or more R 4a It is -OH.

[0129] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a is a halogen. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a is fluoro or chloro. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one R 4a is fluoro. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one R 4a That is Chlorophyll.

[0130] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a is -CN. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one R 4a It is -CN.

[0131] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a C 1~8 It is alkyl, and in this case, C1~8 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a C 1~8 It is alkyl.

[0132] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a C 1~4 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a is methyl, ethyl, propyl, or isopropyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4aIt is methyl.

[0133] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a C 1~8 It is an alkoxy.

[0134] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a -NR 6 R 6 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a is -NH2. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one R 4a It is -NH2.

[0135] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a -NR 7 S(O)2R 9 Therefore, equations I, Ia, In some embodiments of compounds II or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a is -NHS(O)2R 9 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 4a is -NHS(O)2R 9 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 4a is -NHS(O)2(C 1~4 Alkyl) In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one R 4ais -NHS(O)2CH3. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 4a is -NHS(O)2CH2CH3. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 4a is -NHS(O)2(C 3~5 It is a cycloalkyl compound. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 4a It is -NHS(O)2 (cyclopropyl).

[0136] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a -NR 7 S(O)2NR 6 R 6 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a -NR 7 C(O)R 8 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a -NR 7 C(O)R 10 NR 6 R 6 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a -NR 7 C(O)NR 6 R 6 That is the case.

[0137] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 4a is -C(O)NR 6 R 6In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 4a is -C(O)NH2. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 4a It is -C(O)NH2.

[0138] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, 1 to 3 R 4a Two of the R groups 4a It is bonded to the same carbon, and has two R 4a Together with the carbon atoms to which they are bonded, C 3~7 It forms a monocyclic cycloalkyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, 1 to 3 R 4a Two of the R groups 4a It is bonded to the same carbon, and has two R 4a Together with the carbon atoms to which they are bonded, C 3~5 It forms a monocyclic cycloalkyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, 1 to 3 R 4a Two of the R groups 4a It is bonded to the same carbon, and has two R 4a These, together with the carbons to which they are bonded, form cyclopropyl, cyclobutyl, or cyclopentyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, 1 to 3 R 4a Two of the R groups 4a It is bonded to the same carbon, and has two R 4a These, together with the carbon atoms to which they are bonded, form a cyclopropyl group.

[0139] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 This is 1 to 3 R's 4aThe following are arbitrarily substituted in the base: [ka] [ka] [ka]

[0140] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 This is 1 to 3 R's 4a The following are arbitrarily substituted in the base: [ka]

[0141] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 4 This is 1 to 3 R's 4a The following are arbitrarily substituted in the base: [ka] [ka]

[0142] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 6 H and C are independent of each other. 1~8 Alkyl, C 3~7 A monocyclic cycloalkyl, or a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, At this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls and 4-6 membered monocyclic heterocyclils having 1-3 ring heteroatoms independently selected from N, O, and S are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy, or Both R 6 These, together with the nitrogen atoms to which they are bound, form a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0143] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 6 H and C are independent of each other. 1~8 Alkyl, or C 3~7 It is a monocyclic cycloalkyl, At this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy group.

[0144] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 6 H or C 1~4 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 6 It is independently either H or methyl.

[0145] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 6 H is H.

[0146] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 6 C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 6 C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 6 C 1~8 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 6 C 1~4 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 6 It is methyl.

[0147] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 6 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 6 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 6 C 3~7 It is a monocyclic cycloalkyl compound.

[0148] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 6 This is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 6 This is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 6 It is a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0149] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, both R 6 These, together with the nitrogen atoms to which they are bound, form a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0150] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 7 Independently, H or C, which may be the same or different. 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, each R 7 Independently, H or C, which may be the same or different. 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, each R 7 Independently, H or C, which may be the same or different. 1~3 It is alkyl.

[0151] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 7 is H. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 7 C may be the same or different. 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 7 C may be the same or different. 1~8 It is alkyl, and in this case, C 1~8 Alkyl is, -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 7 C may be the same or different. 1~8 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 7 C may be the same or different. 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 7 C may be the same or different. 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 7 C may be the same or different. 1~4 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 7 C may be the same or different. 1~3 It is alkyl.

[0152] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 8 These are independently -OH, C 1~8 Alkyl, C 1~8 Alkoxy, C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 4-6 membered monocyclic heteroaryl. At this time, C 1~8 Alkyl and C 1~8 Alkoxy compounds are, respectively, -OH, halogen, -CN, and C. 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 4-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, the 4-6 membered monocyclic heterocyclyl and the 4-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0153] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 8 These are independently -OH, C 1~8 Alkyl, or C 1~8 It is an alkoxy.

[0154] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 8 It is -OH.

[0155] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 8 C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 1~8 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 8 C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 1 to 3 groups can be optionally placed independently of the alkoxy group. It is replaced. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 1~4 It is alkyl.

[0156] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 8 C 1~8 It is an alkoxy, and in this case, C 1~8 Alkoxy compounds include -OH, halogens, -CN, and C 1~4They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 1~8 It is an alkoxy, and in this case, C 1~8 Alkoxy compounds include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 1~8 It is an alkoxy.

[0157] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 8 C 1~5 It is an alkoxy, and in this case, C 1~5 Alkoxy compounds include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 1~5 It is an alkoxy, and in this case, C 1~5 Alkoxy compounds include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 1~5 It is an alkoxy.

[0158] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 8 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4Alkyl and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 C 3~7 It is a monocyclic cycloalkyl compound.

[0159] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 8 This is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 This is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 It has 1 to 3 ring heteroatoms, independently selected from N, O, and S, and 4 It is a 6-membered monocyclic heterocycline.

[0160] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 8 This is a 4-6 member monocyclic heteroaryl, in which the 4-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 This is a 4-6 member monocyclic heteroaryl, in which the 4-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 8 It is a 4- to 6-membered monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0161] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 9 Independently, C 1~8 Alkyl, C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. At this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0162] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 9 Independently, C 1~8 Alkyl or C 3~7 It is a monocyclic cycloalkyl, At this time, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy group.

[0163] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 9 Independently, C 1~3 Alkyl or C 3~5 It is a monocyclic cycloalkyl compound.

[0164] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 9 C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 C 1~8It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 C 1~8 It is alkyl. Formula I, Ia, II, or I In some embodiments of the compound of Ia, or a pharmaceutically acceptable salt thereof, one or more R 9 C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 C 1~4 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 9 C 1~3 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 9 is methyl, ethyl, propyl, or isopropyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 9 is methyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one R 9is ethyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one R 9 is propyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one R 9 It is isopropyl.

[0165] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 9 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 C 3~7 It is a monocyclic cycloalkyl compound. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 C 3~5 It is a monocyclic cycloalkyl, and in this case, C 3~5 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9C 3~5 It is a monocyclic cycloalkyl, and in this case, C 3~5 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 C 3~5 It is a monocyclic cycloalkyl compound. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one R 9 It is cyclopropyl.

[0166] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 9 This is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 It is a 4-6 member monocyclic heterocyclyl, and in this case, 4-6 A monocyclic heterocyclyl has 1 to 3 ring heteroatoms independently selected from N, O, and S, and contains -OH, halogen, -CN, and C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 It is a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0167] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 9 This is a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 This is a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 9 It is a 5-6 membered monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0168] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 10 C may be the same or different. 1~4 It is an alkylene. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, each R 10 R is independently methylene, ethylene, propylene, isopropylene, butylene, or isobutylene. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 10 It is -CH(CH3)2-.

[0169] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring A, together with the two carbons to which it is bonded, forms a 5-6 membered monocyclic heterocyclil or a 5-6 membered monocyclic heteroaryl, where each 5-6 membered monocyclic heterocyclil and 5-6 membered monocyclic heteroaryl is substituted with one Z group and each has 1-3 ring heteroatoms independently selected from N, O, and S.

[0170] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring A, together with the two carbons to which it is bonded, forms a 5-6 membered monocyclic heterocyclil or a 5-6 membered monocyclic heteroaryl, where each 5-6 membered monocyclic heterocyclil and 5-6 membered monocyclic heteroaryl is substituted with one Z group and each has 1-3 ring heteroatoms independently selected from N, O, and S, where one or two ring heteroatoms are nitrogen.

[0171] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring A, together with the two carbons to which it is bonded, forms a 5-6 membered monocyclic heterocycline, in which case the 5-6 membered monocyclic heterocycline is substituted with one Z group and has 1-3 ring heteroatoms independently selected from N, O, and S. It is substituted with one Z group and has 1 to 3 ring heteroatoms independently selected from N, O, and S, where one or two of the ring heteroatoms are nitrogen.

[0172] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring A, together with the two carbons to which it is bonded, forms a 5-6 membered monocyclic heteroaryl, in which the 5-6 membered monocyclic heteroaryl is substituted with one Z group and has 1-3 ring heteroatoms independently selected from N, O, and S, in which case one or two ring heteroatoms are nitrogen.

[0173] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, [ka] teeth, [ka] That is the case.

[0174] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, [ka] teeth, [ka] That is the case.

[0175] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is i) Oxo, ii)-OH, iii)-CN, iv)C 1~5 It is an alkyl group, and in this case, C 1~5 Alkyl groups consist of -OH and C 1~4 It is substituted with one group selected from alkoxy, in which case C 1~5 The alkyl group is further optionally substituted with one or two groups independently selected from -OH, halogen, and -CN. 1~5 Alkyl, v)C 6~8 It is an alkyl group, and in this case, C 6~8 Alkyls include -OH, halogens, -CN, and C 1~4 C is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 6~8 Alkyl, vi)-Z 1 -Z 2 -Z 3 -Z 4 And, At this time, 1 C 2~6 It is an alkynylene, -OH, halogen, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, 2 and Z 3 Each of them is independent of C 3~7 Monocyclic cycloalkylene, C 6~10 The compound is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, a 5-6 member monocyclic heteroarylene, an 8-10 member condensed or cross-linked bicyclic heterocyclylene, an 8-10 member condensed bicyclic heteroarylene, or a 7-10 member spirocyclic heterocyclylene, in which case C 3~7 Monocyclic cycloalkylene, C 6~10 Monocyclic or condensed bicyclic arylenes, 4-6 member monocyclic heterocyclylenes, 5-6 member monocyclic heteroarylenes, 8-10 member condensed or cross-linked bicyclic heterocyclylenes, 8-10 member condensed bicyclic heteroarylenes, and 7-10 member spirocyclic heterocyclylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from, in which case 4-6 membered monocyclic heterocyclenes, 5-6 membered monocyclic heteroarylenes, 8-10 membered condensed or bridged bicyclic heterocyclenes, 8-10 membered condensed bicyclic heteroarylenes, and 7-10 membered spirocyclic heterocyclenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S. At this time, 4 C 3~7 Monocyclic cycloalkyl, C 6~10 The compound is a monocyclic or condensed bicyclic aryl, a 4-6 member monocyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed or bridged bicyclic heterocyclil, an 8-10 member condensed bicyclic heteroaryl, or a 7-10 member spirocyclic heterocyclil, in which case C 3~7 Monocyclic cycloalkyl, C 6~10 Monocyclic or condensed bicyclic aryls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridged bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclines are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from N, O, and S, in which case 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridging bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils each have 1 to 3 ring heteroatoms independently selected from N, O, and S. -Z 1 -Z 2 -Z 3 -Z 4 , vii)C 3~7 Monocyclic cycloalkyl, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 C is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 3~7Monocyclic cycloalkyl, viii)-S(C 1~8 Alkyl) and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 -S(C) is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 1~8 Alkyl), ix)-NR 11 R 12 And at this time, R 11 and R 12 One of them is H or C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 Alkyl, C 3~7 These are monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, or 7-10 membered spirocyclic heterocyclines. In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base, At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S, -NR 11 R 12 , x)C 6~10 Monocyclic or condensed bicyclic aryls, comprising -OH, halogen, -CN, C1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , -NR 6 R 6 They are optionally substituted with 1 to 3 groups, independently selected from 4-6 membered monocyclic heterocyclines and 5-6 membered monocyclic heteroaryls. In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , and -NR 6 R 6 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, 4-6 membered monocyclic heterocyclyls and 5-6 membered monocyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S, and C 6~10 Monocyclic or fused bicyclic aryl, xi) A 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 A 4-6 member monocyclic heterocycline that is optionally substituted at the base. xii) 8-10 membered condensed or bridging bicyclic heterocyclines having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 8-10 member condensed or cross-linked bicyclic heterocyclines, which are optionally substituted at the base. xiii) A 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 A 5-6 member monocyclic heteroaryl compound that is optionally substituted at the base. xiv) 8-10 membered condensed bicyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13An 8-10 member condensed bicyclic heteroaryl, or, which is optionally substituted at the base. xv) A 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 It is a 7-10 membered spirocyclic heterocycline in which the base is optionally substituted.

[0176] Compounds of formula I, Ia, II, or IIa, or any of their pharmaceutically acceptable salts. In that embodiment, Z is i) Oxo, ii)-OH, iii)-CN, iv)C 1~5 It is an alkyl group, and in this case, C 1~5 Alkyl groups consist of -OH and C 1~4 It is substituted with one group selected from alkoxy, in which case C 1~5 The alkyl group is further optionally substituted with one or two groups independently selected from -OH, halogen, and -CN. 1~5 Alkyl, v)C 6~8 It is an alkyl group, and in this case, C 6~8 Alkyls include -OH, halogens, -CN, and C 1~4 C is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 6~8 Alkyl, vi)-Z 1 -Z 2 -Z 3 -Z 4 And, At this time, 1 C 2~6 It is an alkynylene, -OH, halogen, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, 2 C 6~10 It is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, or a 5-6 member monocyclic heteroarylene, in which case C6~10 Monocyclic or condensed bicyclic arylenes, 4-6 membered monocyclic heterocyclylenes, and 5-6 membered monocyclic heteroarylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from, in which case the 4-6 membered monocyclic heterocyclenes and 5-6 membered monocyclic heteroarylenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S. At this time, 3 These are 5-6 member monocyclic heterocyclylenes or 5-6 member monocyclic heteroarylenes. In this case, the 5-6 member monocyclic heterocyclylene and the 5-6 member monocyclic heteroarylene are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, 4-6 membered monocyclic heterocyclenes and 5-6 membered monocyclic heteroarylenes each have 1-3 ring heteroatoms independently selected from N, O, and S. At this time, 4 These are 5-6 membered monocyclic heterocyclyls or 5-6 membered monocyclic heteroaryls. In this case, 5-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 5-6 member monocyclic heterocyclyl and 5-6 member monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S, and -Z 1 -Z 2 -Z 3 -Z 4 , vii)C 3~7Monocyclic cycloalkyl, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 C is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 3~7 Monocyclic cycloalkyl, viii)-S(C 1~4 Alkyl) and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 -S(C) is optionally substituted with 1 to 3 groups, independently selected from the alkoxy. 1~4 Alkyl), ix)-NR 11 R 12 And at this time, R 11 and R 12 One of them is H or C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 Alkyl, C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17a It is substituted with the base, At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, and 5- The six-membered monocyclic heteroaryls are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S, -NR 11 R 12 , x)C 6~10 Monocyclic or condensed bicyclic aryls, comprising -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR6 R 6 , -C(O)R 8 , -NR 6 R 6 They are optionally substituted with 1 to 3 groups, independently selected from 4-6 membered monocyclic heterocyclines and 5-6 membered monocyclic heteroaryls. In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , and -NR 6 R 6 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, 4-6 membered monocyclic heterocyclyls and 5-6 membered monocyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S, and C 6~10 Monocyclic or fused bicyclic aryl, xi) A 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 A 4-6 member monocyclic heterocycline that is optionally substituted at the base. xii) 8-10 membered condensed or bridging bicyclic heterocyclines having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 8-10 member condensed or cross-linked bicyclic heterocyclines, which are optionally substituted at the base. xiii) A 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 A 5-6 member monocyclic heteroaryl compound that is optionally substituted at the base. xiv) 8-10 member condensed bicyclic heteroaryls, with 1-3 R 13 An 8-10 member condensed bicyclic heteroaryl, or, which is optionally substituted at the base. xv) A 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 It is a 7-10 membered spirocyclic heterocycline in which the base is optionally substituted.

[0177] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is an oxo.

[0178] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -OH or -CN. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -OH. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -CN.

[0179] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 1~5 It is alkyl, and in this case, C 1~5 Alkyl groups consist of -OH and C 1~4 It is substituted with one group selected from alkoxy, in which case C 1~5 The alkyl group is optionally further substituted with one or two groups independently selected from -OH, halogen, and -CN. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 1~5 It is alkyl, and in this case, C 1~5 Alkyl groups consist of -OH and C 1~4 It is substituted with one group selected from alkoxy, in which case C 1~5 The alkyl group is further substituted with one or two groups independently selected from -OH, halogen, and -CN. Formulas I, Ia, II, or In some embodiments of the compound IIa, or its pharmaceutically acceptable salt, Z is C 1~5 It is alkyl, and in this case, C 1~5Alkyl groups consist of -OH and C 1~4 It is substituted with one group independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 1~5 It is alkyl, and in this case, C 1~5 The alkyl group is substituted with one -OH group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -C(CH3)2OH.

[0180] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 6~8 It is alkyl, and in this case, C 6~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 6~8 It is alkyl, and in this case, C 6~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 6~8 It is alkyl.

[0181] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -Z 1 -Z 2 -Z 3 -Z 4 And, At this time, 1 C 2~6 It is an alkynylene, -OH, halogen, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, 2 and Z 3Each of them is independent of C 3~7 Monocyclic cycloalkylene, C 6~10 The compound is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, a 5-6 member monocyclic heteroarylene, an 8-10 member condensed or cross-linked bicyclic heterocyclylene, an 8-10 member condensed bicyclic heteroarylene, or a 7-10 member spirocyclic heterocyclylene, in which case C 3~7 Monocyclic cycloalkylene, C 6~10 Monocyclic or condensed bicyclic arylenes, 4-6 member monocyclic heterocyclylenes, 5-6 member monocyclic heteroarylenes, 8-10 member condensed or cross-linked bicyclic heterocyclylenes, 8-10 member condensed bicyclic heteroarylenes, and 7-10 member spirocyclic heterocyclylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from, in which case 4-6 membered monocyclic heterocyclenes, 5-6 membered monocyclic heteroarylenes, 8-10 membered condensed or bridged bicyclic heterocyclenes, 8-10 membered condensed bicyclic heteroarylenes, and 7-10 membered spirocyclic heterocyclenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S. At this time, 4 C 3~7 Monocyclic cycloalkyl, C 6~10 The compound is a monocyclic or condensed bicyclic aryl, a 4-6 member monocyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed or bridged bicyclic heterocyclil, an 8-10 member condensed bicyclic heteroaryl, or a 7-10 member spirocyclic heterocyclil, in which case C 3~7 Monocyclic cycloalkyl, C 6~10 Monocyclic or condensed bicyclic aryls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridged bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclines are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8They are optionally substituted with 1 to 3 groups independently selected from N, O, and S, in which case 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridging bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils each have 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0182] Compounds of formula I, Ia, II, or IIa, or any of their pharmaceutically acceptable salts. In that embodiment, Z is -Z 1 -Z 2 -Z 3 -Z 4 And, At this time, 1 C 2~6 It is an alkynylene, -OH, halogen, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, 2 C 6~10 It is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, or a 5-6 member monocyclic heteroarylene, in which case C 6~10 Monocyclic or condensed bicyclic arylenes, 4-6 membered monocyclic heterocyclylenes, and 5-6 membered monocyclic heteroarylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from, in which case the 4-6 membered monocyclic heterocyclenes and 5-6 membered monocyclic heteroarylenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S. At this time, 3 These are 5-6 member monocyclic heterocyclylenes or 5-6 member monocyclic heteroarylenes. In this case, the 5-6 member monocyclic heterocyclylene and the 5-6 member monocyclic heteroarylene are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R8 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, 4-6 membered monocyclic heterocyclenes and 5-6 membered monocyclic heteroarylenes each have 1-3 ring heteroatoms independently selected from N, O, and S. At this time, 4 These are 5-6 membered monocyclic heterocyclyls or 5-6 membered monocyclic heteroaryls. In this case, 5-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 5-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0183] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 1 C 2~6 It is an alkynylene, -OH, halogen, -CN, and C 1~4 The alkoxy is optionally substituted with 1 to 3 groups, independently selected. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z 1 C 2~6 It is an alkynylene, -OH, halogen, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 1 C 2~6 It is an alkynylene. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 1 C 2~4 It is an alkynylene, -OH, halogen, -CN, and C 1~4The alkoxy is optionally substituted with 1 to 3 groups, independently selected. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z 1 C 2~4 It is an alkynylene, -OH, halogen, -CN, and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 1 C 2~4 It is an alkynylene. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 1 This is a C2 alkynylene.

[0184] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 3~7 Monocyclic cycloalkylene, C 6~10 The compound is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, a 5-6 member monocyclic heteroarylene, an 8-10 member condensed or cross-linked bicyclic heterocyclylene, an 8-10 member condensed bicyclic heteroarylene, or a 7-10 member spirocyclic heterocyclylene, in which case C 3~7 Single ring type Cycloalkylene, C 6~10 Monocyclic or condensed bicyclic arylenes, 4-6 member monocyclic heterocyclylenes, 5-6 member monocyclic heteroarylenes, 8-10 member condensed or cross-linked bicyclic heterocyclylenes, 8-10 member condensed bicyclic heteroarylenes, and 7-10 member spirocyclic heterocyclylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8They are optionally substituted with 1 to 3 groups independently selected from N, O, and S, in which case 4-6 membered monocyclic heterocyclylenes, 5-6 membered monocyclic heteroarylenes, 8-10 membered condensed or bridged bicyclic heterocyclylenes, 8-10 membered condensed bicyclic heteroarylenes, and 7-10 membered spirocyclic heterocyclylenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0185] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 6~10 It is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, or a 5-6 member monocyclic heteroarylene, in which case C 6~10 Monocyclic or condensed bicyclic arylenes, 4-6 membered monocyclic heterocyclylenes, and 5-6 membered monocyclic heteroarylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from N, O, and S, in which case the 4-6 membered monocyclic heterocyclenes and 5-6 membered monocyclic heteroarylenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0186] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 3~7 It is a monocyclic cycloalkylene, and in this case, C 3~7 Monocyclic cycloalkylenes are -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 3~7 It is a monocyclic cycloalkylene, and in this case, C 3~7Monocyclic cycloalkylenes are -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 3~7 It is a monocyclic cycloalkylene.

[0187] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 6~10 It is a monocyclic or condensed bicyclic arylene, and in this case, C 6~10 Monocyclic or bicyclic arylenes include -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 6~10 It is a monocyclic or condensed bicyclic arylene, and in this case, C 6~10 Monocyclic or bicyclic arylenes include -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 6~10 It is a monocyclic or condensed bicyclic arylene. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 It is phenylene.

[0188] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2This is a 4-6 member monocyclic heterocyclene, in which the 4-6 member monocyclic heterocyclene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is independently selected and optionally substituted by 1 to 3 elements. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 This is a 4-6 member monocyclic heterocyclene, in which the 4-6 member monocyclic heterocyclene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 It is a 4-6 membered monocyclic heterocyclene having 1-3 ring heteroatoms independently selected from N, O, and S.

[0189] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 This is a 5-6 member monocyclic heteroarylene, in which the 5-6 member monocyclic heteroarylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 This is a 5-6 member monocyclic heteroarylene, in which the 5-6 member monocyclic heteroarylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 It is a 5-6 membered monocyclic heteroarylene having 1-3 ring heteroatoms independently selected from N, O, and S.

[0190] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 This is an 8-10 member condensed or bridged bicyclic heterocyclylene, in which the 8-10 member condensed or bridged bicyclic heterocyclylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 This is an 8-10 member condensed or bridged bicyclic heterocyclylene, in which the 8-10 member condensed or bridged bicyclic heterocyclylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 This is an 8-10 membered condensed or bridged bicyclic heterocyclene having 1-3 ring heteroatoms independently selected from N, O, and S.

[0191] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2This is an 8-10 membered condensed bicyclic heteroarylene, in which the 8-10 membered condensed bicyclic heteroarylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 This is an 8-10 membered condensed bicyclic heteroarylene, in which the 8-10 membered condensed bicyclic heteroarylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 It is selected independently from N, O, and S. It is an 8-10 membered condensed bicyclic heteroarylene having 1-3 ring heteroatoms.

[0192] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 This is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2This is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 It is a 7-10 membered spirocyclic heterocyclene having 1-3 ring heteroatoms independently selected from N, O, and S.

[0193] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 1 It is a C2 alkynylene, and Z 2 It is phenylene.

[0194] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 C 3~7 Monocyclic cycloalkylene, C 6~10 The compound is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, a 5-6 member monocyclic heteroarylene, an 8-10 member condensed or cross-linked bicyclic heterocyclylene, an 8-10 member condensed bicyclic heteroarylene, or a 7-10 member spirocyclic heterocyclylene, in which case C 3~7 Monocyclic cycloalkylene, C 6~10 Monocyclic or condensed bicyclic arylenes, 4-6 member monocyclic heterocyclylenes, 5-6 member monocyclic heteroarylenes, 8-10 member condensed or cross-linked bicyclic heterocyclylenes, 8-10 member condensed bicyclic heteroarylenes, and 7-10 member spirocyclic heterocyclylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8They are optionally substituted with 1 to 3 groups independently selected from N, O, and S, in which case 4-6 membered monocyclic heterocyclylenes, 5-6 membered monocyclic heteroarylenes, 8-10 membered condensed or bridged bicyclic heterocyclylenes, 8-10 membered condensed bicyclic heteroarylenes, and 7-10 membered spirocyclic heterocyclylenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0195] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 These are 5-6 member monocyclic heterocyclylene or 5-6 member monocyclic heteroarylene, where 5-6 member monocyclic heterocyclylene and 5-6 member monocyclic heteroarylene are -OH, halogen, -CN, and C, respectively. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from N, O, and S, in which case the 5-6 membered monocyclic heterocyclene and the 5-6 membered monocyclic heteroarylene each have 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0196] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 C 3~7 It is a monocyclic cycloalkylene, and in this case, C 3~7 Monocyclic cycloalkylenes are -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 C 3~7 It is a monocyclic cycloalkylene, and in this case, C 3~7 Monocyclic cycloalkylenes are -OH, halogen, -CN, C 1~4 Al Kill, C 1~4Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 C 3~7 It is a monocyclic cycloalkylene.

[0197] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 C 6~10 It is a monocyclic or condensed bicyclic arylene, and in this case, C 6~10 Monocyclic or bicyclic arylenes include -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 C 6~10 It is a monocyclic or condensed bicyclic arylene, and in this case, C 6~10 Monocyclic or bicyclic arylenes include -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 C 6~10 It is a monocyclic or condensed bicyclic arylene.

[0198] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is a 4-6 member monocyclic heterocyclene, in which the 4-6 member monocyclic heterocyclene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is a 4-6 member monocyclic heterocyclene, in which the 4-6 member monocyclic heterocyclene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 It is a 4-6 membered monocyclic heterocyclene having 1-3 ring heteroatoms independently selected from N, O, and S.

[0199] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is a 5-6 member monocyclic heteroarylene, in which the 5-6 member monocyclic heteroarylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is a 5-6 member monocyclic heteroarylene, in which the 5-6 member monocyclic heteroarylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3This is a 5-6 membered monocyclic heteroarylene having 1-3 ring heteroatoms independently selected from N, O, and S. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 It is imidazoline.

[0200] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is an 8-10 member condensed or bridged bicyclic heterocyclylene, in which the 8-10 member condensed or bridged bicyclic heterocyclylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 a Lu kill, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is an 8-10 member condensed or bridged bicyclic heterocyclylene, in which the 8-10 member condensed or bridged bicyclic heterocyclylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is an 8-10 membered condensed or bridged bicyclic heterocyclene having 1-3 ring heteroatoms independently selected from N, O, and S.

[0201] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3This is an 8-10 membered condensed bicyclic heteroarylene, in which the 8-10 membered condensed bicyclic heteroarylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is an 8-10 membered condensed bicyclic heteroarylene, in which the 8-10 membered condensed bicyclic heteroarylene has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 It is an 8-10 membered condensed bicyclic heteroarylene having 1-3 ring heteroatoms independently selected from N, O, and S.

[0202] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 This is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3This is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 3 It is a 7-10 membered spirocyclic heterocyclene having 1-3 ring heteroatoms independently selected from N, O, and S.

[0203] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 C 3~7 Monocyclic cycloalkyl, C 6~10 The compound is a monocyclic or condensed bicyclic aryl, a 4-6 member monocyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed or bridged bicyclic heterocyclil, an 8-10 member condensed bicyclic heteroaryl, or a 7-10 member spirocyclic heterocyclil, in which case C 3~7 Monocyclic cycloalkyl, C 6~10 Monocyclic or condensed bicyclic aryls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridged bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclines are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from the above, in which case it is a 4-6 member monocyclic heterocyclyl, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed or bridging bicyclic heterocyclyl. Rocyclyls, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclyls each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0204] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 These are 5-6 member monocyclic heterocyclils or 5-6 member monocyclic heteroaryls, where the 5-6 member monocyclic heterocyclils and 5-6 member monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from N, O, and S, in which case the 5-6 membered monocyclic heterocyclil and 5-6 membered monocyclic heteroaryl each have 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0205] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 C 3~7 It is a monocyclic cycloalkyl compound.

[0206] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4C 6~10 It is a monocyclic or fused bicyclic aryl, and in this case, C 6~10 Monocyclic or condensed bicyclic aryls include -OH, halogens, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 C 6~10 It is a monocyclic or fused bicyclic aryl, and in this case, C 6~10 Monocyclic or condensed bicyclic aryls include -OH, halogens, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 C 6~10 It is a monocyclic or fused bicyclic aryl.

[0207] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 It is a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0208] Compounds of formula I, Ia, II, or IIa, or any of their pharmaceutically acceptable salts. In that embodiment, Z 4 This is a 5-6 member monocyclic heterocycline, in which the 5-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with one group selected from. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is a 5-6 member monocyclic heterocycline, in which the 5-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is substituted with one group selected from. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 It is a 5-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0209] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8A pyrrolidinyl compound independently selected from, substituted with 1 to 3 groups. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 is one -C(O)R 8 It is pyrrolidinyl, which is substituted with. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 It is pyrrolidinil.

[0210] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 It is a 5-6 membered monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0211] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4This is an 8-10 membered condensed or bridged bicyclic heterocycline, in which the 8-10 membered condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is an 8-10 membered condensed or bridged bicyclic heterocycline, in which the 8-10 membered condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 It is an 8-10 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0212] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4This is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 It is an 8-10 membered condensed bicyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0213] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is optionally substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 This is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 Substituted with 1 to 3 groups independently selected from. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 4 It is a 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0214] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z 2 C 6~10 It is a monocyclic or condensed bicyclic arylene, a 4-6 member monocyclic heterocyclylene, or a 5-6 member monocyclic heteroarylene, in which case C 6~10 Monocyclic or condensed bicyclic arylenes, 4-6 membered monocyclic heterocyclylenes, and 5-6 membered monocyclic heteroarylenes are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 They are optionally substituted with 1 to 3 groups independently selected from, in which case the 4-6 membered monocyclic heterocyclenes and 5-6 membered monocyclic heteroarylenes each have 1 to 3 ring heteroatoms independently selected from N, O, and S. Z 3 These are 5-6 member monocyclic heterocyclylenes or 5-6 member monocyclic heteroarylenes. In this case, the 5-6 member monocyclic heterocyclylene and the 5-6 member monocyclic heteroarylene are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy and -C(O)R 8 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 5-6 membered monocyclic heterocyclene and the 5-6 membered monocyclic heteroarylene each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0215] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 3~7 Monocyclic cycloalkyl or -S(C 1~4 It is alkyl, and in this case, C 3~7 Monocyclic cycloalkyl and C 1~4 Alkyl groups are -OH, halogen, -CN, and C, respectively. 1~4It is optionally substituted with one or two groups independently selected from the alkoxy. Compounds of formula I, Ia, II, or IIa, or the same In some embodiments of the pharmaceutically acceptable salt, Z is C 3~7 Monocyclic cycloalkyl or -S(C 1~4 It is alkyl, and in this case, C 3~7 Monocyclic cycloalkyl and C 1~4 Alkyl groups are -OH, halogen, -CN, and C, respectively. 1~4 It is substituted with one or two groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 3~7 Monocyclic cycloalkyl or -S(C 1~4 It is alkyl.

[0216] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 3~7It is a monocyclic cycloalkyl compound. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is cyclopropyl, cyclobutyl, or cyclopentyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is cyclopropyl.

[0217] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -S(C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -S(C 1~8 It is alkyl, and in this case, C 1~8 Alkyls include -OH, halogens, -CN, and C 1~4 It is substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -S(C 1~8 It is alkyl.

[0218] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -S(C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -S(C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, -CN, and C 1~4It is substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -S(C 1~4 Z is alkyl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -S(methyl), -S(ethyl), -S(propyl), or -S(isopropyl). In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is -S(CH3).

[0219] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H or C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 Alkyl, C 3~7 Monocyclic cycloalkyl, 4-6 member monocyclic heterocyclil, 5-6 member monocyclic heteroaryl, 8-10 member condensed or cross-linked bicyclic heterocyclil, 8-10 member condensed bicyclic It is a heteroaryl or a 7-10 membered spirocyclic heterocycline. In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base, At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0220] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H or C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 Alkyl, C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17a It is substituted with the base, At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 5-6 membered monocyclic heteroaryls are classified as oxo, -OH, halogen, -CN, and C, respectively. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0221] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~8 Alkyl, C 3~7These are monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, or 7-10 membered spirocyclic heterocyclines. In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base, At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0222] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~8 It is alkyl, and in this case, C 1~8 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base.

[0223] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12One of them is H, and R 11 and R 12 The other of these is C 1~6 It is alkyl, and at this time , C 1~6 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base.

[0224] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~8 It is alkyl, and in this case, C 1~8 Alkyl groups consist of 1 to 3 R's. 17a It is substituted with the base.

[0225] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~6 It is alkyl, and in this case, C 1~6 Alkyl groups consist of 1 to 3 R's. 17a It is substituted with the base.

[0226] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~6 It is alkyl, and in this case, C 1~6The alkyl group is substituted with 1 to 3 groups independently selected from -OH, halogen, and -CN.

[0227] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~6 It is alkyl, and in this case, C 1~6 Alkyl is C 1~4 Alkoxy and -NR 6 R 6 It is substituted with 1 to 3 groups that are independently selected from, and in this case, C 1~4 Alkoxy is a single C 1~4 It is optionally substituted with an alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~6 It is alkyl, and in this case, C 1~6 Alkyl groups include -OH, methoxy, -OCH2CH2OCH3, or -N(C) 1~3 It is substituted with one group selected from alkyl)2, in which case each C 1~3 Alkyls may be the same or different.

[0228] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~6 It is alkyl, and in this case, C 1~6 Alkyl groups consist of 1 to 3 R's. 17aIt is substituted with the base.

[0229] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 1~6 It is alkyl, and in this case, C 1~6 The alkyl group is substituted with one group selected from cyclopropyl, morpholinyl, and imidazolyl, where cyclopropyl, morpholinyl, and imidazolyl are -OH, halogen, and C, respectively. 1~4 It is optionally substituted with one group selected from alkoxy groups.

[0230] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And in this case, -NR 11 R 12 teeth, [ka] That is the case.

[0231] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. At this time, C 3~7Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 5-6 membered monocyclic heteroaryls are classified as oxo, -OH, halogen, -CN, and C, respectively. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0232] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is cyclopropyl, oxetanyl, tetrahydrofuranyl, or pyrrolidinyl, each of which is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy group.

[0233] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 5-6 membered monocyclic heteroaryls are classified as oxo, -OH, halogen, -CN, and C, respectively. 1~4 Alkyl and C 1~4 It is substituted with 1 to 3 groups independently selected from the alkoxy, In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0234] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is cyclopropyl, oxetanyl, tetrahydrofuranyl, or pyrrolidinyl, each of which is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 It is substituted with 1 to 3 groups, independently selected from the alkoxy group.

[0235] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, and 5- The six-membered monocyclic heteroaryls are, respectively, oxo and C. 1~4 It is optionally substituted with 1 to 3 groups that are independently selected from alkyl groups. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0236] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. At this time, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, and 5-6 membered monocyclic heteroaryls are each classified as oxo and C, respectively. 1~4 Substituted with 1 to 3 groups independently selected from alkyl groups, In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0237] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, a 4-6 membered monocyclic heterocyclyl, or a 5-6 membered monocyclic heteroaryl. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is cyclopropyl, oxetanil, tetrahydrofuranil, or pyrrolidinil.

[0238] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl compound.

[0239] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is cyclopropyl, in which case cyclopropyl is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is cyclopropyl, in which case cyclopropyl is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is cyclopropyl.

[0240] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 4-6 member monocyclic heterocyclil, in which case the 4-6 member monocyclic heterocyclil has 1-3 ring heteroatoms independently selected from N, O, and S, and is composed of oxo, -OH, halogen, -CN, and C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 4-6 member monocyclic heterocyclil, in which case the 4-6 member monocyclic heterocyclil has 1-3 ring heteroatoms independently selected from N, O, and S, and is composed of oxo, -OH, halogen, -CN, and C1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0241] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is oxetanil, tetrahydrofuranil, or pyrrolidinil, in which case oxetanil, tetrahydrofuranil, and pyrrolidinil are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is oxetanil, tetrahydrofuranil, or pyrrolidinil, in which case oxetanil, tetrahydrofuranil, and pyrrolidinil are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R12 The other of these is oxetanil, tetrahydrofuranil, or pyrrolidinil.

[0242] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 5-6 member monocyclic heteroaryl, in which case the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 5-6 member monocyclic heteroaryl, in which case the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0243] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is pyrazolyl, in which case pyrazolyl is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is pyrazolyl, in which case pyrazolyl is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is pyrazolyl.

[0244] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is an 8-10 member condensed or bridged bicyclic heterocycline, in which case the 8-10 member condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R11 and R 12 One of them is H, and R 11 and R 12 The other of these is an 8-10 member condensed or bridged bicyclic heterocycline, in which case the 8-10 member condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is an 8-10 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0245] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is an 8-10 membered condensed bicyclic heteroaryl, in which case the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12The other of these is an 8-10 membered condensed bicyclic heteroaryl, in which case the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is an 8-10 membered condensed bicyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0246] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 7-10 membered spirocyclic heterocycline. In this case, the 7-10 membered spirocyclic heterocyclyl has 1-3 ring heteroatoms independently selected from N, O, and S, and contains oxo, -OH, halogen, -CN, and C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 7-10 membered spirocyclic heterocycline, in which case the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is H, and R 11 and R 12 The other of these is a 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0247] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And in this case, -NR 11 R 12 teeth, [ka] That is the case.

[0248] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 Alkyl, C 3~7 These are monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, or 7-10 membered spirocyclic heterocyclines. In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base, At this time, C 3~7Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0249] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 It is alkyl, In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base.

[0250] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~6 It is alkyl, R 11 and R 12 The other of these is C 1~6 It is alkyl, In this case, each C 1~6 Alkyl groups consist of 1 to 3 R's. 17 It is substituted with the base.

[0251] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is C 1~8 It is alkyl, In this case, each C 1~8 Alkyl groups consist of 1 to 3 R's. 17a It is substituted with the base.

[0252] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~6 It is alkyl, R 11 and R 12 The other of these is C 1~6 It is alkyl, In this case, each C 1~6 Alkyl groups consist of 1 to 3 R's. 17a It is substituted with the base.

[0253] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 17 These are independently -OH, halogen, -CN, and C 1~4 Alkoxy, -NR 6 R 6 , C 3~7 These include monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclines. At this time, C 1~4 Alkoxy, C 3~7Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclils, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or cross-linked bicyclic heterocyclils, 8-10 membered condensed bicyclic heteroaryls, and 7-10 membered spirocyclic heterocyclils are, respectively, oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0254] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 17a These are independently -OH, halogen, -CN, and C 1~4 Alkoxy, -NR 6 R 6 , C 3~7 These are monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclines, and 5-6 membered monocyclic heteroaryls. At this time, C 1~4 Alkoxy, C 3~7 Monocyclic cycloalkyls, 4-6 membered monocyclic heterocyclyls, and 5-6 membered monocyclic heteroaryls are classified as oxo, -OH, halogen, -CN, and C, respectively. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0255] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl, and in this case, C 3~7 Monocyclic cycloalkyls include oxo, -OH, halogen, -CN, and C. 1~4 Alkyl and C 1~4 Selected independently from alkoxy, 1~ It is substituted with three groups. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is C 3~7 It is a monocyclic cycloalkyl compound.

[0256] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12The other of these is a 4-6 member monocyclic heterocyclil, in which case the 4-6 member monocyclic heterocyclil has 1-3 ring heteroatoms independently selected from N, O, and S, and is composed of oxo, -OH, halogen, -CN, and C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is a 4-6 member monocyclic heterocyclil, in which case the 4-6 member monocyclic heterocyclil has 1-3 ring heteroatoms independently selected from N, O, and S, and is composed of oxo, -OH, halogen, -CN, and C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0257] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is a 5-6 member monocyclic heteroaryl, in which case the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is a 5-6 member monocyclic heteroaryl, in which case the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is a 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0258] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is an 8-10 member condensed or bridged bicyclic heterocycline, in which case the 8-10 member condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is an 8-10 member condensed or bridging bicyclic heterocycline, in which case the 8-10 member condensed or bridging bicyclic heterocycline is independently selected from N, O, and S, and contains 1-3 ring heterogens. It has offspring, oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is an 8-10 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0259] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is an 8-10 membered condensed bicyclic heteroaryl, in which case the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is an 8-10 membered condensed bicyclic heteroaryl, in which case the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is an 8-10 membered condensed bicyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0260] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is -NR 11 R 12 And at this time, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is a 7-10 membered spirocyclic heterocycline, in which case the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 It is optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is a 7-10 membered spirocyclic heterocycline, in which case the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and is oxo, -OH, halogen, -CN, C 1~4 Alkyl and C 1~4 Substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, R 11 and R 12 One of them is C 1~8 It is alkyl, R 11 and R 12 The other of these is a 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0261] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 6~10 It is a monocyclic or condensed bicyclic aryl, containing -OH, halogen, -CN, or C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , -NR 6 R 6 They are optionally substituted with 1 to 3 groups, independently selected from 4-6 membered monocyclic heterocyclines and 5-6 membered monocyclic heteroaryls. In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , and -NR 6 R 6 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0262] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 6~10 It is a monocyclic or condensed bicyclic aryl, containing -OH, halogen, -CN, or C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , -NR 6 R 6 Substituted with 1 to 3 groups independently selected from 4-6 membered monocyclic heterocyclyls and 5-6 membered monocyclic heteroaryls, In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , and -NR 6 R 6 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0263] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is C 6~10 It is a monocyclic or fused bicyclic aryl.

[0264] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is phenyl, -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR6 R 6 , -C(O)R 8 , -NR 6 R 6 They are optionally substituted with 1 to 3 groups, independently selected from 4-6 membered monocyclic heterocyclines and 5-6 membered monocyclic heteroaryls. In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , and -NR 6 R 6 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0265] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is phenyl, -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , -NR 6 R 6 Substituted with 1 to 3 groups independently selected from 4-6 membered monocyclic heterocyclyls and 5-6 membered monocyclic heteroaryls, In this case, 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls are, respectively, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 , and -NR 6 R 6 It is arbitrarily substituted with 1 to 3 elements, which are selected independently of each other. In this case, the 4-6 membered monocyclic heterocyclyl and the 5-6 membered monocyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0266] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is phenyl, in which case phenyl is -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 The group is optionally substituted with 1 to 3 groups independently selected from 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls, in which case the 4-6 membered monocyclic heterocyclil and the 5-6 membered monocyclic heteroaryl each have one -C(O)R group. 8 It is optionally replaced 、 Furthermore, each has 1 to 3 ring heteroatoms independently selected from N, O, and S. Compounds of formula I, Ia, II, or IIa, or their pharmaceutically In some embodiments of the acceptable salt, Z is phenyl, in which case phenyl is -OH, halogen, -CN, C 1~4 Alkyl, C 1~4 Alkoxy, -C(O)NR 6 R 6 , -C(O)R 8 The group is substituted with 1 to 3 groups independently selected from 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls, where each of the 4-6 membered monocyclic heterocyclils and 5-6 membered monocyclic heteroaryls has one -C(O)R group. 8 It is optionally replaced 、 Furthermore, each has 1 to 3 ring heteroatoms independently selected from N, O, and S.

[0267] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is phenyl, in which case phenyl is a halogen, -C(O)NR 6 R6 It is optionally substituted with 1 to 3 groups independently selected from morpholinyl or piperazinyl, in which case morpholinyl and piperazinyl each have one -C(O)R 8 It is optionally substituted with. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is phenyl, in which case phenyl is a halogen, -C(O)NR 6 R 6 It is substituted with 1 to 3 groups independently selected from morpholinyl or piperazinyl, in which case morpholinyl and piperazinyl each have one -C(O)R 8 It is being replaced by an arbitrary choice.

[0268] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is [ka] That is the case.

[0269] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is phenyl.

[0270] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 4-6 member monocyclic heterocyclil, an 8-10 member condensed or bridged bicyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed bicyclic heteroaryl, or a 7-10 member spirocyclic heterocyclil, where each of the 4-6 member monocyclic heterocyclil, 8-10 member condensed or bridged bicyclic heterocyclil, 5-6 member monocyclic heteroaryl, 8-10 member condensed bicyclic heteroaryl, and 7-10 member spirocyclic heterocyclil contains 1-3 R 13 The group is optionally substituted with a group and has 1 to 3 ring heteroatoms, each independently selected from N, O, and S.

[0271] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 4-6 member monocyclic heterocyclil, an 8-10 member condensed or bridged bicyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed bicyclic heteroaryl, or a 7-10 member spirocyclic heterocyclil, where the 4-6 member monocyclic heterocyclil, the 8-10 member condensed or bridged bicyclic heterocyclil, the 5-6 member monocyclic heteroaryl, the 8-10 member condensed bicyclic heteroaryl, and the 7-10 member spirocyclic heterocyclil are Each of them has 1 to 3 R's 13 The ring heteroatoms are optionally substituted with a group, and each is independently selected from N, O, and S, with at least one ring heteroatom being nitrogen.

[0272] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 4-6 member monocyclic heterocyclil, an 8-10 member condensed or bridged bicyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed bicyclic heteroaryl, or a 7-10 member spirocyclic heterocyclil, where each of the 4-6 member monocyclic heterocyclil, 8-10 member condensed or bridged bicyclic heterocyclil, 5-6 member monocyclic heteroaryl, 8-10 member condensed bicyclic heteroaryl, and 7-10 member spirocyclic heterocyclil contains 1-2 R 13 The group is optionally substituted with a group and has 1 to 3 ring heteroatoms, each independently selected from N, O, and S.

[0273] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 4-6 member monocyclic heterocyclil, an 8-10 member condensed or bridged bicyclic heterocyclil, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed bicyclic heteroaryl, or a 7-10 member spirocyclic heterocyclil, where each of the 4-6 member monocyclic heterocyclil, 8-10 member condensed or bridged bicyclic heterocyclil, 5-6 member monocyclic heteroaryl, 8-10 member condensed bicyclic heteroaryl, and 7-10 member spirocyclic heterocyclil contains 1-2 R 13 The ring heteroatoms are optionally substituted with a group, and each is independently selected from N, O, and S, with at least one ring heteroatom being nitrogen.

[0274] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is azetidinil, pyrrolidinil, morpholinil, piperazinil, piperidinil, pyrazolyl, imidazolyl, pyrimidinil, isoindolinil, 2-oxa-6-azaspiro[3.3]heptanil, 2,5-diazabicyclo[2.2.1]heptanil, 2,6-diazaspiro[3.3]heptanil, 1,6-diazaspiro[3.3]heptanil, 2,7-diazaspiro[3.5]nonanil, 1-oxa-3,8-diazaspiro[4.5]decanil, or 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinil, each of which contains 1 to 3 R 13 It is optionally substituted in the base.

[0275] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is azetidinil, pyrrolidinil, morpholinil, piperazinil, piperidinil, pyrazolyl, imidazolyl, pyrimidinil, isoindolinil, 2-oxa-6-azaspiro[3.3]heptanil, 2,5-diazabicyclo[2.2.1]heptanil, 2,6-diazaspiro[3.3]heptanil, 1,6-diazaspiro[3.3]heptanil, 2,7-diazaspiro[3.5]nonanil, 1-oxa-3,8-diazaspiro[4.5]decanil, or 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinil, each of which contains 1-2 R 13 It is optionally substituted in the base.

[0276] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is azetidinil, pyrrolidinil, morpholinil, piperazinil, piperidinil, pyrazolyl, imidazolyl, pyrimidinil, isoindolinil, 2-oxa-6-azaspiro[3.3]heptanil, 2,5-diazabicyclo[2.2.1]heptanil, 2,6-diazaspiro[3.3]heptanil, 1,6-diazaspiro[3.3]heptanil, 2,7-diazaspiro[3.5]nonanil, 1-oxa-3,8-diazaspiro[4.5]decanil, or 5,6,7,8-tetrahydro-[1,2,4]triazo [4,3-a]pyrazinyl, each of which contains 1 to 3 R 13 It is substituted with the base.

[0277] In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, Z is azetidinil, pyrrolidinil, morpholinil, piperazinil, piperidinil, pyrazolyl, imidazolyl, pyrimidinil, isoindolinil, 2-oxa-6-azaspiro[3.3]heptanil, 2,5-diazabicyclo[2.2.1]heptanil, 2,6-diazaspiro[3.3]heptanil, 1,6-diazaspiro[3.3]heptanil, 2,7-diazaspiro[3.5]nonanil, 1-oxa-3,8-diazaspiro[4.5]decanil, or 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinil, each of which contains 1-2 R 13 It is substituted with the base.

[0278] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is azetidinil, pyrrolidinil, morpholinil, piperazinil, piperidinil, pyrazolyl, imidazolyl, pyrimidinil, isoindolinil, 2-oxa-6-azaspiro[3.3]heptanil, 2,5-diazabicyclo[2.2.1]heptanil, 2,6-diazaspiro[3.3]heptanil, 1,6-diazaspiro[3.3]heptanil, 2,7-diazaspiro[3.5]nonanil, 1-oxa-3,8-diazaspiro[4.5]decanil, or 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinil.

[0279] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 4- to 6-membered monocyclic heterocycline, where the 4- to 6-membered monocyclic heterocycline has 1 to 3 ring heteroatoms independently selected from N, O, and S, and 1 to 3 R 13 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 4- to 6-membered monocyclic heterocycline, where the 4- to 6-membered monocyclic heterocycline has 1 to 3 ring heteroatoms independently selected from N, O, and S, and 1 to 3 R13 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms, independently selected from N, O, and S.

[0280] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is azetidinil, pyrrolidinil, morpholinil, piperazinil, or piperidinil, where azetidinil, pyrrolidinil, morpholinil, piperazinil, and piperidinil each contain 1 to 3 R 13 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is azetidinyl, pyrrolidinyl, morpholinyl, piperazinyl, or piperidinyl, where azetidinyl, pyrrolidinyl, morpholinyl, piperazinyl, and piperidinyl each contain 1 to 3 R groups. 13 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is azetidinil, pyrrolidinil, morpholinil, piperazinil, or piperidinil.

[0281] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is an 8-10 membered condensed or bridging bicyclic heterocycline, where the 8-10 membered condensed or bridging bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 The group is optionally substituted. Compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts In some embodiments, Z is an 8-10 membered condensed or bridging bicyclic heterocycline, in which case the 8-10 membered condensed or bridging bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is an 8-10 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms, independently selected from N, O, and S.

[0282] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is 2,5-diazabicyclo[2.2.1]heptanyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyradinyl, or 2,3-dihydrobenzo[b][1,4]dioxynyl, where 2,5-diazabicyclo[2.2.1]heptanyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyradinyl, and 2,3-dihydrobenzo[b][1,4]dioxynyl each contain 1 to 3 R 13 The group is optionally substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is 2,5-diazabicyclo[2.2.1]heptanyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyradinyl, or 2,3-dihydrobenzo[b][1,4]dioxynyl, where 2,5-diazabicyclo[2.2.1]heptanyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyradinyl, and 2,3-dihydrobenzo[b][1,4]dioxynyl each contain 1 to 3 R groups. 13 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is 2,5-diazabicyclo[2.2.1]heptanyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, or 2,3-dihydrobenzo[b][1,4]dioxynyl.

[0283] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 5-6 membered monocyclic heteroaryl, where the 5-6 membered monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 5-6 membered monocyclic heteroaryl, in which the 5-6 membered monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 5-6 membered monocyclic heteroaryl having 1-3 ring heteroatoms, independently selected from N, O, and S.

[0284] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is pyrazolyl, imidazolyl, pyrimidinil, isoindolinil, pyrazolyl, imidazolyl, or pyrimidinil, where pyrazolyl, imidazolyl, pyrimidinil, isoindolinil, pyrazolyl, imidazolyl, and pyrimidinil each contain 1 to 3 R 13 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is pyrazolyl, imidazolyl, pyrimidinyl, isoindolinyl, pyrazolyl, imidazolyl, or pyrimidinyl, where pyrazolyl, imidazolyl, pyrimidinyl, isoindolinyl, pyrazolyl, imidazolyl, and pyrimidinyl each contain 1 to 3 R groups. 13 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is pyrazolyl, imidazolyl, pyrimidinyl, isoindolinyl, pyrazolyl, imidazolyl, or pyrimidinyl.

[0285] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is an 8-10 membered condensed bicyclic heteroaryl, where the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is an 8-10 membered condensed bicyclic heteroaryl having 1-3 ring heteroatoms, independently selected from N, O, and S.

[0286] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is isoindlinyl or 1H-benzo[d]imidazolyl, where isoindlinyl and 1H-benzo[d]imidazolyl each contain 1 to 3 R 13 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is isoindlinyl or 1H-benzo[d]imidazolyl, in which case isoindlinyl and 1H-benzo[d]imidazolyl each contain 1 to 3 R groups. 13 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is isoindolinyl or 1H-benzo[d]imidazolyl.

[0287] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 7-10 membered spirocyclic heterocycline, where the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 7-10 membered spirocyclic heterocycline, where the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 13 It is substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is a 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0288] In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 1,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, or 1-oxa-3,8-diazaspiro[4.5]decanyl, where 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 1,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, and 1-oxa-3,8-diazaspiro[4.5]decanyl each contain 1 to 3 R 13The group is optionally substituted with a group. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 1,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, or 1-oxa-3,8-diazaspiro[4.5]decanyl, where 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 1,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, and 1-oxa-3,8-diazaspiro[4.5]decanyl each have 1 to 3 R groups. 13 It is substituted with the base. Formulas I, Ia, II, or II In some embodiments of compound a, or a pharmaceutically acceptable salt thereof, Z is 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 1,6-diazaspiro[3.3]heptanyl, 2,7-diazaspiro[3.5]nonanyl, or 1-oxa-3,8-diazaspiro[4.5]decanyl.

[0289] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is [ka] And, During the ceremony, Ring Z a These are 4-6 member monocyclic heterocyclils, 8-10 member condensed or bridged bicyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed bicyclic heteroaryls, or 7-10 member spirocyclic heterocyclils, where each of the 4-6 member monocyclic heterocyclils, 8-10 member condensed or bridged bicyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils has one ring heteroatom which is nitrogen, and each has one or two additional ring heteroatoms which are independently selected from N, O, and S. Ring Z a This is 1 to 3 R's 13 It is optionally substituted in the base.

[0290] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, Z is [ka] And, During the ceremony, Ring Z a These are 4-6 member monocyclic heterocyclils, 8-10 member condensed or bridged bicyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed bicyclic heteroaryls, or 7-10 member spirocyclic heterocyclils, where each of the 4-6 member monocyclic heterocyclils, 8-10 member condensed or bridged bicyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils has one ring heteroatom which is nitrogen, and each has one or two ring heteroatoms which are independently selected from N, O, and S. Ring Z a is 1-2 R 13 It is optionally substituted in the base.

[0291] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring Z a teeth, [ka] And, Each of these has 1 to 3 R's. 13 It is optionally substituted in the base.

[0292] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, ring Z a teeth, [ka] And, Each of these is 1-2 R 13 It is optionally substituted in the base.

[0293] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 13 These are independently oxo, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -NR 6 R 6 , -C(O)R 10 NR 6 R 6 -C(O)NR 6 R 6 , -C(O)R 8 , C 6~10 These are monocyclic or condensed bicyclic aryls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridged bicyclic heterocyclines, 8-10 membered condensed bicyclic heteroaryls, or 7-10 membered spirocyclic heterocyclines. At this time, C 6~10 Monocyclic or condensed bicyclic aryls, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 R 14 It is optionally substituted in the base, In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0294] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 13 These are independently oxo, -OH, halogen, -CN, and C. 1~ 4 alkyl, C 1~4 Alkoxy, -NR 6 R 6 , -C(O)R 10 NR 6 R 6 -C(O)NR 6 R 6 , -C(O)R 8 , C 6~10 These are monocyclic or condensed bicyclic aryls, 4-6 membered monocyclic heterocyclines, 5-6 membered monocyclic heteroaryls, 8-10 membered condensed or bridged bicyclic heterocyclines, or 8-10 membered condensed bicyclic heteroaryls. At this time, C 6~10 Monocyclic or condensed bicyclic aryls, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, and 8-10 member condensed bicyclic heteroaryls each have 1-3 R 14 It is optionally substituted in the base, In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, and 8-10 member condensed bicyclic heteroaryls each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0295] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 13 These are independently oxo, -OH, halogen, -CN, and C. 1~4 Alkyl, C 1~4 Alkoxy, -NR 6 R 6 , -C(O)R 10 NR 6 R 6 -C(O)NR 6 R 6 , -C(O)R 8 , C 6~10 The compound is a monocyclic or condensed bicyclic aryl, a 4-6 member monocyclic heterocyclyl, a 5-6 member monocyclic heteroaryl, an 8-10 member condensed or bridged bicyclic heterocyclyl, or an 8-10 member condensed bicyclic heteroaryl, in which case C 6~10 Monocyclic or fused bicyclic aryls have 1 to 3 R14 The group is optionally substituted, in which case the 4-6 member monocyclic heterocyclil, 5-6 member monocyclic heteroaryl, 8-10 member condensed or bridging bicyclic heterocyclil, and 8-10 member condensed bicyclic heteroaryl each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0296] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 13 These are independently oxo, -OH, halogen, methyl, ethyl, isopropyl, and -NR. 6 R 6 , -C(O)R 10 NR 6 R 6 -C(O)NR 6 R 6 , -C(O)R 8 , phenyl, oxetanyl, 2,3-dihydrobenzo[b][1,4]dioxynyl, pyridinyl, pyrimidinyl, or 1H-benzo[d]imidazolyl, in which case phenyl has one R 14 It is optionally substituted in the base.

[0297] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 is an oxo. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 13 is -OH. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 is a halogen. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 is -CN. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 C 1~4It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 C 1~4 It is an alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 -NR 6 R 6 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 13 is -C(O)R 10 NR 6 R 6 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 13 is -C(O)NR 6 R 6 In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 13 is -C(O)R 8 That is the case.

[0298] Compounds of formula I, Ia, II, or IIa, or any of their pharmaceutically acceptable salts. In that embodiment, one or more R 13 C 6~10 It is a monocyclic or fused bicyclic aryl, and in this case, C 6~10 Monocyclic or fused bicyclic aryls have 1 to 3 R 14 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R groups are present. 13 C 6~10 It is a monocyclic or fused bicyclic aryl, and in this case, C 6~10 Monocyclic or fused bicyclic aryls have 1 to 3 R 14 Substituted with a group. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 C 6~10It is a monocyclic or fused bicyclic aryl.

[0299] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 It is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R groups are present. 13 It is a 4-6 member monocyclic heterocycline, in which the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 Substituted with a group. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 It is a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0300] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 This is a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R groups are present. 13 This is a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 Substituted with a group. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13It is a 5-6 membered monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0301] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 This is an 8-10 membered condensed or bridged bicyclic heterocycline, in which the 8-10 membered condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R groups are present. 13 This is an 8-10 membered condensed or bridged bicyclic heterocycline, in which the 8-10 membered condensed or bridged bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 Substituted with a group. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 It is an 8-10 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0302] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 This is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 The base is optionally replaced In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 This is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14Substituted with a group. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 It is an 8-10 membered condensed bicyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0303] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 It is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 The group is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R groups are present. 13 It is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and 1-3 R 14 Substituted with a group. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 13 It is a 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0304] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 14 These are, independently, halogen, C 1~4 Alkyl, -C(O)R 8 These are 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, or 7-10 member spirocyclic heterocyclils. At this time, C 1~4 Alkyls include -OH, halogens, CN, and C 1~4It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridged bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils are each C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted, In this case, 4-6 member monocyclic heterocyclils, 5-6 member monocyclic heteroaryls, 8-10 member condensed or bridging bicyclic heterocyclils, 8-10 member condensed bicyclic heteroaryls, and 7-10 member spirocyclic heterocyclils each have 1-3 ring heteroatoms independently selected from N, O, and S.

[0305] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 14 These are, independently, halogen, C 1~4 Alkyl, -C(O)R 8 , or a 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S, At this time, C 1~4 Alkyls include -OH, halogens, CN, and C 1~4 It is optionally substituted with 1 to 3 groups, which are independently selected from the alkoxy. At this time, a 5-6 member monocyclic heteroaryl having 1-3 ring heteroatoms, independently selected from N, O, and S, is C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted.

[0306] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 14These are, independently, halogen, C 1~4 Alkyl, or 5-6 member groups It is a monocyclic heteroaryl, At this time, C 1~4 Alkyl groups are optionally substituted with 1 to 3 halogens. In this case, the 5-6 membered heteroaryl is optionally substituted with -CH2OCH2CH2Si(CH3)3 and has 1-3 ring heteroatoms independently selected from N, O, and S.

[0307] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 14 These are, independently, halogen, C 1~4 It is alkyl or imidazolyl, and in this case, C 1~4 The alkyl group is optionally substituted with 1 to 3 halogens, and in this case, the imidazolyl group is optionally substituted with -CH2OCH2CH2Si(CH3)3.

[0308] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 is a halogen. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 is -C(O)R 8 That is the case.

[0309] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 C 1~4 It is alkyl, and in this case, C 1~4 Alkyls include -OH, halogens, CN, and C 1~4 They are optionally substituted with 1 to 3 groups independently selected from the alkoxy. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 C 1~4 It is alkyl, and in this case, C1~4 Alkyls include -OH, halogens, CN, and C 1~4 It is substituted with 1 to 3 groups, independently selected from the alkoxy group.

[0310] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 C 1~4 It is alkyl, and in this case, C 1~4 The alkyl group is optionally substituted with 1 to 3 halogens. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 C 1~4 It is alkyl, and in this case, C 1~4 Alkyl groups are substituted with 1 to 3 halogens.

[0311] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 C 1~4 It is alkyl.

[0312] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 It is a 4-6 member monocyclic heterocycline, in which case the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 It is a 4-6 member monocyclic heterocycline, in which case the 4-6 member monocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is substituted with alkyl, and in this case, C 1~3Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 It is a 4-6 membered monocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0313] Compounds of formula I, Ia, II, or IIa, or any of their pharmaceutically acceptable salts. In that embodiment, one or more R 14 This is a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 This is a 5-6 member monocyclic heteroaryl, in which the 5-6 member monocyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is substituted with alkyl, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 It is a 5-6 membered monocyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0314] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 This is imidazolyl, and in this case, imidazolyl is C 1~3It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 This is imidazolyl, and in this case, imidazolyl is C 1~3 It is substituted with alkyl, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 is imidazolyl, in which case imidazolyl is optionally substituted with -CH2OCH2CH2Si(CH3)3. In some embodiments of the compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 It is imidazolyl.

[0315] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 This is an 8-10 member condensed or bridging bicyclic heterocycline, in which case the 8-10 member condensed or bridging bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 This is an 8-10 member condensed or bridging bicyclic heterocycline, in which case the 8-10 member condensed or bridging bicyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is substituted with alkyl, and in this case, C 1~3Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 It is an 8-10 membered condensed or bridging bicyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0316] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14 This is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 This is an 8-10 membered condensed bicyclic heteroaryl, in which the 8-10 membered condensed bicyclic heteroaryl has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is substituted with alkyl, and this At that time, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 It is an 8-10 membered condensed bicyclic heteroaryl having 1-3 ring heteroatoms independently selected from N, O, and S.

[0317] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 14This is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is optionally substituted with an alkyl group, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 This is a 7-10 membered spirocyclic heterocycline, in which the 7-10 membered spirocyclic heterocycline has 1-3 ring heteroatoms independently selected from N, O, and S, and C 1~3 It is substituted with alkyl, and in this case, C 1~3 Alkyl is -OR 10 Si(R 15 )3 is optionally substituted. In some embodiments of the compounds of formula I, Ia, II, or IIa, or their pharmaceutically acceptable salts, one or more R 14 It is a 7-10 membered spirocyclic heterocycline having 1-3 ring heteroatoms independently selected from N, O, and S.

[0318] In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, each R 15 C can be independent and may be the same or different. 1~3 It is alkyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 15 is methyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 15 is ethyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R 15 is propyl. In some embodiments of compounds of formula I, Ia, II, or IIa, or pharmaceutically acceptable salts thereof, one or more R15 It is isopropyl.

[0319] In some embodiments of the compounds of formula I, Ia, II, or IIa, the compound is [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] Alternatively, it is selected from the group consisting of pharmaceutically acceptable salts thereof.

[0320] In one embodiment, the compound provided herein has the following structure: [ka] or a pharmaceutically acceptable salt thereof. III. Compositions and Kits

[0321] The compounds provided herein are typically administered in the form of pharmaceutical compositions. Accordingly, pharmaceutical compositions comprising one or more of the compounds provided herein, or their pharmaceutically acceptable salts, isomers, or mixtures, and one or more pharmaceutically acceptable vehicles selected from carriers, auxiliaries, and excipients are also provided herein. The compounds provided herein may be the sole active ingredient or one of the active ingredients of a pharmaceutical composition. Suitable pharmaceutically acceptable vehicles in...

Claims

[Claim 1] A retroviral virus infection.

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