Tea d inhibitors and methods of use thereof

Abstract

The present disclosure provides compounds and methods for modulating or inhibiting TEADs. Further provided herein are pharmaceutical compositions comprising these TEAD inhibitors, and methods of treatment using these TEAD inhibitors or these pharmaceutical compositions.

Description

Cross-references

[0001] This patent application claims the benefit of International Application No. PCT / CN2024 / 084120, filed on March 27, 2024, which is incorporated herein by reference in its entirety. Background Technology

[0002] The Hippo pathway is a signaling pathway that regulates cell proliferation and cell death and determines organ size. It is believed to function as a tumor suppressor in mammals and its abnormalities are frequently detected in human cancers. This pathway is involved in and / or may regulate the self-renewal and differentiation of stem cells and progenitor cells. Furthermore, the Hippo pathway may be involved in wound healing and tissue regeneration. In addition, it is believed that due to crosstalk with other signaling pathways such as Wnt, Notch, Hedgehog, and MAPK / ERK, the Hippo pathway may affect a variety of biological events, and its dysfunction may be associated with many human diseases beyond cancer.

[0003] Unphosphorylated activated YAP translocates to the nucleus, where its primary target transcription factors are four proteins (TEAD1-TEAD4, collectively referred to as "TEAD") containing the TEAD domain. YAP has been shown to co-induce the expression of multiple genes, including connective tissue growth factor (CTGF), Gli2, Birc5, Birc2, fibroblast growth factor 1 (FGF1), and amphotericin G (AREG), with TEAD. Like YAP, unphosphorylated TAZ translocates to the nucleus, where it interacts with various DNA-binding transcription factors, such as peroxisome proliferator-activated receptor γ (PPARγ), thyroid transcription factor-1 (TTF-1), Pax3, TBX5, RUNX, TEAD1, and Smad2 / 3 / 4. Many genes activated by the YAP / TAZ-transcription factor complex mediate cell survival and proliferation. Therefore, under certain conditions, YAP and / or TAZ function as oncogenes, while the Hippo pathway functions as a tumor suppressor. Summary of the Invention

[0004] This article discloses compounds that are TEAD inhibitors, or pharmaceutically acceptable salts or stereoisomers thereof.

[0005] This article discloses a compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof: Equation (I) is as described in this article.

[0006] This article also discloses a pharmaceutical composition comprising the compound disclosed herein, or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.

[0007] A method for treating cancer in a subject in need, the method comprising administering to the subject in need an effective amount of the compound disclosed herein, or a pharmaceutically acceptable salt or stereoisomer thereof.

[0008] In some embodiments of the method for treating cancer, the cancer is mesothelioma. In some embodiments of the method for treating cancer, the cancer is NF2-deficient mesothelioma.

[0009] In some embodiments of methods for treating cancer, the cancer is epithelioid hemangioendothelioma.

[0010] In some embodiments of methods for treating cancer, the cancer is a solid tumor.

[0011] In some embodiments of the method for treating cancer, the solid tumor has an NF2 mutation, a LATS1 mutation, a LATS2 mutation, or any combination thereof. In some embodiments of the method for treating cancer, the solid tumor has an NF2 mutation. In some embodiments of the method for treating cancer, the solid tumor has a LATS1 mutation. In some embodiments of the method for treating cancer, the solid tumor has a LATS2 mutation. In some embodiments of the method for treating cancer, the solid tumor has a YAP1 / TAZ gene fusion. By incorporating via reference

[0012] All publications, patents and patent applications mentioned in this specification are incorporated herein by reference to the same extent that each individual publication, patent or patent application is specifically and individually indicated to be incorporated by reference. Detailed Implementation definition

[0013] In the following description, certain specific details are set forth to provide a thorough understanding of various embodiments. However, those skilled in the art will understand that the invention can be practiced without these details. In other instances, well-known structures are not shown or described in detail to avoid unnecessarily obscuring the description of the embodiments. Unless the context requires otherwise, throughout this specification and the following claims, the word “comprise” and its variations such as “comprises” and “comprising” should be interpreted in an open, inclusive sense, meaning “including but not limited to”. Furthermore, the headings provided herein are for convenience only and do not constitute an explanation of the scope or meaning of the claimed invention.

[0014] Throughout this specification, references to "some embodiments" or "one embodiment" mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment. Therefore, the phrase "in one embodiment" appearing throughout this specification does not necessarily refer to the same embodiment. Furthermore, a particular feature, structure, or characteristic may be combined in one or more embodiments in any suitable manner. And, as used in this specification and the appended claims, the singular forms "a / an," "a / an," and "the" include plural references unless expressly stated otherwise. It should also be noted that the term "or" is generally used in its meaning including "and / or" unless expressly stated otherwise.

[0015] Unless otherwise indicated, the following terms have the following meanings as used herein:

[0016] "Oxytochemical" refers to the compound oxygen (O).

[0017] "Carboxyl group" refers to -COOH.

[0018] "Cyano" refers to -CN.

[0019] "alkyl" refers to a monovalent group of a straight-chain or branched saturated hydrocarbon having one to ten carbon atoms, more preferably one to six carbon atoms. Examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, and hexyl, as well as longer alkyl groups such as heptyl and octyl. Whenever used herein, numerical ranges such as “C1-C6 alkyl” or “C1-6 alkyl” mean that an alkyl group can consist of 1, 2, 3, 4, 5, or 6 carbon atoms, although this definition also covers the use of the term “alkyl” when no numerical range is specified. In some embodiments, an alkyl group is C1- 10Alkyl group. In some embodiments, the alkyl group is C1-6 alkyl. In some embodiments, the alkyl group is C1-5 alkyl. In some embodiments, the alkyl group is C1-4 alkyl. In some embodiments, the alkyl group is C1-3 alkyl. Unless otherwise specifically stated in this specification, the alkyl group may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxy, haloalkyl, alkoxy, carboxyl, carboxyl ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkyl group is optionally substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkyl group is optionally substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkyl group is optionally substituted with halogen.

[0020] "Alkenyl" refers to a monovalent group of a straight-chain or branched hydrocarbon having one or more carbon-carbon double bonds and having two to ten carbon atoms, more preferably two to six carbon atoms. This group may be in a cis or trans conformation around the double bond and should be understood to include both isomers. Examples include, but are not limited to, vinyl (-CH=CH2), 1-propenyl (-CH2CH=CH2), isopropenyl (-C(CH3)=CH2), butenyl, 1,3-butadienyl, etc. Whenever it appears herein, numerical ranges such as "C2-C6 alkenyl" or "C2-6 alkenyl" mean that the alkenyl group may consist of 2, 3, 4, 5, or 6 carbon atoms, although this definition also covers the occurrence of the term "alkenyl" when no numerical range is specified. Unless otherwise specifically stated in this specification, the alkenyl group may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkenyl group may optionally be substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkenyl group may optionally be substituted with halogen, -CN, -OH, or -OMe. In some embodiments, the alkenyl group may optionally be substituted with halogen.

[0021] "Alynyl" refers to a monovalent group of a straight-chain or branched hydrocarbon having one or more carbon-carbon triple bonds and having two to ten carbon atoms, more preferably two to six carbon atoms. Examples include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1,3-butadiynyl, etc. Whenever it appears herein, numerical ranges such as "C2-C6 alkynyl" or "C2-6 alkynyl" mean that the alkynyl group can consist of 2, 3, 4, 5, or 6 carbon atoms, although this definition also covers the occurrence of the term "alkynyl" when no numerical range is specified. Unless otherwise specifically stated in this specification, the alkynyl group may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the alkynyl group is optionally substituted with an oxo group, a halogen group, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, the alkynyl group is optionally substituted with a halogen group, -CN, -OH, or -OMe. In some embodiments, the alkynyl group is optionally substituted with a halogen group.

[0022] "alkylene" refers to a straight-chain or branched divalent hydrocarbon chain. Unless otherwise specifically stated in this specification, alkylene may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxyl ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, alkylene may optionally be substituted with oxo, halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, alkylene may optionally be substituted with halogen, -CN, -OH, or -OMe. In some embodiments, alkylene may optionally be substituted with halogen.

[0023] "alkylidenyl" is an alkenyl group as defined above, linked by a terminal divalent carbon. For example, in the following compounds: The alkylidene group is surrounded by the box indicated by the arrow.

[0024] "Alkoxy" refers to a group having the formula -O alkyl, wherein the alkyl group is as defined above. Unless otherwise specifically stated in this specification, an alkoxy group may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, an alkoxy group may optionally be substituted with halogen, -CN, -COOH, -COOMe, -OH, -OMe, -NH2, or -NO2. In some embodiments, an alkoxy group may optionally be substituted with halogen, -CN, -OH, or -OMe. In some embodiments, an alkoxy group may optionally be substituted with halogen.

[0025] "Aryl" refers to a group derived from a hydrocarbon ring system containing 6 to 30 carbon atoms and at least one aromatic ring. Aryl groups can be monocyclic, bicyclic, tricyclic, or tetracyclic ring systems, which can include fused ring systems (where the aryl group is bonded to aromatic ring atoms when fused with a cycloalkyl or heterocyclic alkyl ring) or bridged ring systems. In some embodiments, the aryl group is a 6- to 10-membered aryl group. In some embodiments, the aryl group is a 6-membered aryl (phenyl). Aryl groups include, but are not limited to, aryl groups derived from the following hydrocarbon ring systems: anthracene, naphthyl, phenanthrene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, asymmetric indole, symmetric indole, indane, indene, naphthalene, phenalene, pleiadene, pyrene, and triphenylene. Unless otherwise specifically stated in this specification, the aryl group may optionally be substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the aryl group may optionally be substituted with halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the aryl group may optionally be substituted with halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the aryl group may optionally be substituted with halogen.

[0026] "Cycloalkyl" refers to a partially or fully saturated monocyclic or polycyclic carbon ring, which may include fused ring systems (where the cycloalkyl is bonded to non-aromatic ring atoms when fused with an aryl or heteroaryl ring), spirocyclic ring systems, or bridged ring systems. In some embodiments, the cycloalkyl is fully saturated. Representative cycloalkyl groups include, but are not limited to, those having three to fifteen carbon atoms (e.g., C3-C4). 15 Fully saturated cycloalkyl or C3-C 15 Cycloalkenyl), three to ten carbon atoms (e.g., C3-C) 10 Fully saturated cycloalkyl or C3-C 10Cycloalkyl groups are cycloalkyl groups comprising three to eight carbon atoms (e.g., C3-C8 fully saturated cycloalkyl or C3-C8 cycloalkyl), three to six carbon atoms (e.g., C3-C6 fully saturated cycloalkyl or C3-C6 cycloalkyl), three to five carbon atoms (e.g., C3-C5 fully saturated cycloalkyl or C3-C5 cycloalkyl), or three to four carbon atoms (e.g., C3-C4 fully saturated cycloalkyl or C3-C4 cycloalkyl). In some embodiments, the cycloalkyl group is a 3- to 10-membered fully saturated cycloalkyl or a 3- to 10-membered cycloalkyl. In some embodiments, the cycloalkyl group is a 3- to 6-membered fully saturated cycloalkyl or a 3- to 6-membered cycloalkyl. In some embodiments, the cycloalkyl group is a 5- to 6-membered fully saturated cycloalkyl or a 5- to 6-membered cycloalkyl. Monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl groups include, for example, adamantyl, norbornel, decahydronaphthyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decahydronaphthyl, trans-decahydronaphthyl, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, and bicyclo[3.3.2]decane, as well as 7,7-dimethyl-bicyclo[2.2.1]heptyl. Partially saturated cycloalkyl groups include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless otherwise specifically stated in this specification, cycloalkyl groups may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxyl ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, the cycloalkyl group is optionally substituted with an oxo, halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the cycloalkyl group is optionally substituted with an oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the cycloalkyl group is optionally substituted with a halogen.

[0027] "Halogen" or "halogen" refers to bromine, chlorine, fluorine, or iodine. In some embodiments, the halogen is fluorine or chlorine. In some embodiments, the halogen is fluorine.

[0028] "Halogenated alkyl" refers to an alkyl group as defined above that is substituted with one or more halogenated groups as defined above, such as trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, etc.

[0029] "Hydroxyalkyl" refers to an alkyl group as defined above that is substituted with one or more hydroxyl groups. In some embodiments, the alkyl group is substituted with one hydroxyl group. In some embodiments, the alkyl group is substituted with one, two, or three hydroxyl groups. Hydroxyalkyl groups include, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl group is hydroxymethyl.

[0030] "Aminoalkyl" refers to an alkyl group as defined above that is substituted with one or more amines. In some embodiments, the alkyl group is substituted with one amine. In some embodiments, the alkyl group is substituted with one, two, or three amines. Aminoalkyl groups include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the aminoalkyl group is aminomethyl.

[0031] "Heteroalkyl" refers to an alkyl group in which one or more skeletal atoms of the alkyl group are selected from atoms other than carbon (e.g., oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or combinations thereof). The heteroalkyl group is attached to the remainder of the molecule at a carbon atom of the heteroalkyl group. In one aspect, a heteroalkyl group is a C1-C6 heteroalkyl group, wherein the heteroalkyl group consists of 1 to 6 carbon atoms and one or more atoms other than carbon (e.g., oxygen, nitrogen (e.g., -NH-, -N(alkyl)-), sulfur, phosphorus, or combinations thereof), wherein the heteroalkyl group is attached to the remainder of the molecule at a carbon atom of the heteroalkyl group. Examples of such heteroalkyl groups are, for example, -CH2OCH3, -CH2CH2OCH3, -CH2CH2OCH2CH2OCH3, -CH(CH3)OCH3, -CH2NHCH3, -CH2N(CH3)2, -CH2CH2NHCH3, or -CH2CH2N(CH3)2. Unless otherwise specifically stated in this specification, heteroalkyl groups are optionally substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc. In some embodiments, heteroalkyl groups are optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, heteroalkyl groups are optionally substituted with oxo, halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, heteroalkyl groups are optionally substituted with halogens.

[0032] "Heterocyclic alkyl" refers to a 3- to 24-membered partially saturated or fully saturated cyclic group comprising 2 to 23 carbon atoms and 1 to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, silicon, and sulfur. In some embodiments, the heterocyclic alkyl is fully saturated. In some embodiments, the heterocyclic alkyl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the heterocyclic alkyl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, the heterocyclic alkyl comprises one to three nitrogen atoms. In some embodiments, the heterocyclic alkyl comprises one or two nitrogen atoms. In some embodiments, the heterocyclic alkyl comprises one nitrogen atom. In some embodiments, the heterocyclic alkyl comprises one nitrogen atom and one oxygen atom. Unless otherwise specifically stated in this specification, the heterocyclic alkyl can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include a fused ring system (when fused with an aryl or heteroaryl ring, the heterocyclic alkyl is bonded by non-aromatic ring atoms), a spirocyclic ring system, or a bridged ring system; and the nitrogen, carbon, or sulfur atom in the heterocyclic alkyl may optionally be oxidized; the nitrogen atom may optionally be quaternized. Representative heterocyclic alkyl groups include, but are not limited to, those having two to fifteen carbon atoms (e.g., C2-C). 15 Fully saturated heterocyclic alkyl or C2-C 15 Heterocyclic alkenyl groups, two to ten carbon atoms (e.g., C2-C) 10 Fully saturated heterocyclic alkyl or C2-C 10Heterocyclic alkyl groups consisting of two to eight carbon atoms (e.g., C2-C8 fully saturated heterocyclic alkyl or C2-C8 heterocyclic alkyl), two to seven carbon atoms (e.g., C2-C7 fully saturated heterocyclic alkyl or C2-C7 heterocyclic alkyl), two to six carbon atoms (e.g., C2-C6 fully saturated heterocyclic alkyl or C2-C6 heterocyclic alkyl), two to five carbon atoms (e.g., C2-C5 fully saturated heterocyclic alkyl or C2-C5 heterocyclic alkyl), or two to four carbon atoms (e.g., C2-C4 fully saturated heterocyclic alkyl or C2-C4 heterocyclic alkyl). Examples of such heterocyclic alkyl groups include, but are not limited to, aziridinyl, aziridine, oxacyclobutyl, dioxopentyl, thienyl[1,3]dithiaalkyl, decahydroisoquinolinyl, imidazolinyl, imidazoalkyl, isothiazolinyl, isoxazolinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperidinyl, 2-oxopiperidinyl, 2-oxopiperidinyl, oxazolinyl, piperidinyl, piperazinyl, 4-piperidinoneyl, pyrroleyl. Pyrazolyl, quininecycloyl, thiazoyl, tetrahydrofuranyl, trithiayl, tetrahydropyranyl, thiomorpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxacyclopenten-4-yl, and 2-oxo-1,3-dioxacyclopenten-4-yl. The term heterocyclic alkyl also includes all cyclic forms of carbohydrates, including but not limited to monosaccharides, disaccharides, and oligosaccharides. In some embodiments, a heterocyclic alkyl group has 2 to 10 carbon atoms in the ring. It should be understood that when referring to the number of carbon atoms in a heterocyclic alkyl group, the number of carbon atoms in the heterocyclic alkyl group is different from the total number of atoms (including heteroatoms) constituting the heterocyclic alkyl group (i.e., the skeletal atoms of the heterocyclic alkyl ring). In some embodiments, a heterocyclic alkyl group is a 3- to 8-membered heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 7-membered heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 6-membered heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 4- to 6-membered heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 5- to 6-membered heterocyclic alkyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 8-membered heterocyclic alkenyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 7-membered heterocyclic alkenyl group. In some embodiments, the heterocyclic alkyl group is a 3- to 6-membered heterocyclic alkenyl group. In some embodiments, the heterocyclic alkyl group is a 4- to 6-membered heterocyclic alkenyl group. In some embodiments, the heterocyclic alkyl group is a 5- to 6-membered heterocyclic alkenyl group. Unless otherwise specifically stated in this specification, the heterocyclic alkyl group may optionally be substituted with, for example, oxo, halogen, amino, nitrile, nitro, hydroxy, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylate, aryl, cycloalkyl, heterocyclic alkyl, heteroaryl, etc., as described below.In some embodiments, the heterocyclic alkyl group is optionally substituted with an oxo, halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heterocyclic alkyl group is optionally substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heterocyclic alkyl group is optionally substituted with a halogen.

[0033] "Heteroaryl" refers to a 5- to 14-membered ring system group comprising one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorus, and sulfur, and at least one aromatic ring. In some embodiments, a heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, a heteroaryl comprises one to three heteroatoms selected from the group consisting of nitrogen and oxygen. In some embodiments, a heteroaryl comprises one to three nitrogen atoms. In some embodiments, a heteroaryl comprises one or two nitrogen atoms. In some embodiments, a heteroaryl comprises one nitrogen atom. A heteroaryl can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include a fused ring system (when fused with a cycloalkyl ring or a heterocyclic alkyl ring, the heteroaryl is bonded by aromatic ring atoms) or a bridged ring system; and the nitrogen, carbon, or sulfur atom in the heteroaryl may optionally be oxidized; the nitrogen atom may optionally be quaternized. In some embodiments, a heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments, a heteroaryl is a 5- to 6-membered heteroaryl. In some embodiments, a heteroaryl is a 6-membered heteroaryl. In some embodiments, the heteroaryl group is a 5-membered heteroaryl group. Examples include, but are not limited to, azepinyl, acridine, benzimidazolyl, benzothiazolyl, benzoindolyl, benzodioxacyclopentenyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxacycloheptatrienyl, 1,4-benzodioxylalkyl, benzonaphthofuranyl, benzooxazolyl, benzodioxacyclohexenyl, benzopyranyl, benzopyranoneyl, benzofuranyl, benzofuranoneyl, benzothienyl / benzothiophenyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridyl, carbazole, cenylyl, dibenzofuranyl, dibenzothienyl, furazolyl, etc. The following groups are listed: nylonyl, furanoneyl, isothiazolyl, imidazolyl, indazole, indolyl, isoindolyl, indololinyl, isoindololinyl, isoquinolinyl, indolazinyl, isoxazolyl, naphridinyl, oxadiazolyl, 2-oxoazapyridine, oxazolyl, ethylene oxide, 1-pyridinyl oxide, 1-pyrimidinyl oxide, 1-pyrazinyl oxide, 1-pyridazinyl oxide, 1-phenyl-1H-pyrroleyl, phenazinyl, phenothiazinyl, phenothiazinyl, phthalazinyl, pteridinyl, purine, pyrroleyl, pyrazolyl, pyridinyl, pyridinyl, pyridinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quininecycloyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless otherwise specified in this specification, heteroaryl groups may optionally be substituted with, for example, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, carboxyl, carboxylic acid ester, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, etc.In some embodiments, the heteroaryl group is optionally substituted with a halogen, methyl, ethyl, -CN, -COOH, -COOMe, -CF3, -OH, -OMe, -NH2, or -NO2. In some embodiments, the heteroaryl group is optionally substituted with a halogen, methyl, ethyl, -CN, -CF3, -OH, or -OMe. In some embodiments, the heteroaryl group is optionally substituted with a halogen.

[0034] The terms “optional” or “optionally” mean that the event or situation described below may or may not occur, and the description includes both the scenario where said event or situation occurs and the scenario where said event or situation does not occur. For example, “optionally substituted alkyl” means “alkyl” or “substituted alkyl” as defined above. Furthermore, the optionally substituted group can be unsubstituted (e.g., -CH2CH3), fully substituted (e.g., -CF2CF3), monosubstituted (e.g., -CH2CH2F), or substituted at any level between full and monosubstituted (e.g., -CH2CHF2, -CH2CF3, -CF2CH3, -CFHCHF2, etc.). Those skilled in the art will understand that for any group containing one or more substituents, such groups are not intended to introduce any spatially impractical and / or synthetically infeasible substitution or substitution pattern. Therefore, any substituent should generally be understood to have a maximum molecular weight of about 1,000 Daltons, and more typically, at most about 500 Daltons.

[0035] When referring to optional substituents, the term "one or more" means that the subject group is optionally substituted by one, two, three, four, or more substituents. In some embodiments, the subject group is optionally substituted by one, two, three, or four substituents. In some embodiments, the subject group is optionally substituted by one, two, or three substituents. In some embodiments, the subject group is optionally substituted by one or two substituents. In some embodiments, the subject group is optionally substituted by one substituent. In some embodiments, the subject group is optionally substituted by two substituents.

[0036] "Effective dose" or "therapeutic effective dose" refers to the amount of a compound administered to a mammalian subject as a single dose or as part of a series of doses that effectively produces the desired therapeutic effect.

[0037] As used herein, the terms “treat,” “treating,” or “treatment” include relieving, reducing, or improving at least one symptom of a disease or condition, preventing additional symptoms, suppressing a disease or condition, such as preventing the development of a disease or condition, alleviating a disease or condition, causing a disease or condition to subside, relieving a condition caused by a disease or condition, or terminating the symptoms of a disease or condition.

[0038] As used in this article, “a disease or condition associated with TEAD”, or alternatively, “a disease or condition mediated by TEAD”, means any disease or other harmful ailment in which TEAD or its mutants are known or suspected to play a role. compound

[0039] This article describes compounds, or pharmaceutically acceptable salts or stereoisomers thereof, that can be used to treat diseases or conditions associated with TEAD.

[0040] This article discloses a compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof: Formula (I), in: X is -N- or -CR X -; R X It is hydrogen, halogen, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 ynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, ynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Y is -N-, -CR Y -or-C(=O)-; R Y It is hydrogen, halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 ynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, ynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Ring A is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; Each R 1 Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a-S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl); wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally separated by one or more R 1a replace; Or two R atoms on the same atom 1 Together they form oxygen; Each R 1a Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d-NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 1a Together they form oxygen; n is 0, 1, 2, 3 or 4; Each L 1 and L 2 It does not exist independently, or it is -O-, -S-, or -NR. 2 -、-C(R 3 )2-、-C(R 3 )2-C(R 3 )2-、-C(R 3 )=C(R 3 )-、 -C(R) 3 )2O-、-OC(R 3 )2-、-C(R 3 )2S-、-SC(R 3 )2-、-C(R 3 )2NR 2 -or-NR 2 C(R 3 )2-; R 2 It is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 ynyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, alkenyl, ynyl, cycloalkyl and heterocycloalkyl is independently and optionally substituted by one or more R; Each R 3Independently, it is hydrogen, halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 ynyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, alkenyl, ynyl, cycloalkyl and heterocycloalkyl is independently and optionally substituted by one or more R; Or two Rs on the same carbon 3 Together they form oxygen; Or two Rs on the same carbon 3 Together they form a cycloalkyl or heterocycloalkyl group; each of the cycloalkyl or heterocycloalkyl group is optionally substituted with one or more R groups; Or two R on different carbons 3 Together they form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; each of the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group may optionally be substituted with one or more R groups. The ring C is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; Each R 7 It is independently hydrogen, halogen, -OH, or C1-C6 alkyl; p is 0, 1, 2, 3, 4, 5 or 6; R 8 It is hydrogen, -C(=O)OR 9 -C(=O)NR 10 R 11 -C(=O)R 9 -S(=O)2NR 10 R 11 , -S(=O)2R 9 -S(=O)R 9 -P(=O)(OR) 10 (OR) 11 ) or -B (OR 10 (OR) 11 ); R 9 It is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally influenced by one or more R 9a replace; Each R 9a Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 9a Together they form oxygen; R 10 and R 11 Each of the following is independently hydrogen, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally influenced by one or more R10a replace; or R 10 and R 11 Together with the atoms they are attached to, they form a group optionally bounded by one or more R atoms. 10b Substituted heterocyclic alkyl groups; Each R 10a Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 10a Together they form oxygen; Each R 10b Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NRc R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 10b Together they form oxygen; U is -C- or -N-; T is either -C- or -N-; The conditions are that U and T are not both -N-; and that U and T are both -C- when ring B is phenyl or a 6-membered heteroaryl. Ring B is absent, or is phenyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocycloalkyl, or C5-C7 cycloalkyl; Each R 12 Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a-S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 12 Together they form oxygen; Or two Rs on the same carbon 12 Together they form a cycloalkyl or heterocycloalkyl group; each of the cycloalkyl or heterocycloalkyl group is optionally substituted with one or more R groups; Or two R on different atoms 12 Together they form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; each of the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group may optionally be substituted with one or more R groups. m is 0, 1, 2, 3, 4, 5, or 6; Or an R 12 and R Y Together they form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; each of the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group may optionally be substituted with one or more R groups. Each R aIndependently, it is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl) or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Each R b Independently, it is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl) or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; R c and R d Each of the following is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl) or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; or R c and R d Together with the atoms to which they are attached, they form heterocyclic alkyl groups optionally substituted with one or more R atoms; and Each R is independently a halogen, -CN, -OH, -SF5, -SH, -S(=O)C1-C3 alkyl, -S(=O)2C1-C3 alkyl, -S(=O)2NH2, -S(=O)2NHC1-C3 alkyl, -S(=O)2N(C1-C3 alkyl)2, -S(=O)(=NC1-C3 alkyl)(C1-C3 alkyl), -NH2, -NHC1-C3 alkyl, -N(C1-C3 alkyl)2, -N=S(=O)(C1-C3 alkyl) 2. -C(=O)C1-C3 alkyl, -C(=O)OH, -C(=O)OC1-C3 alkyl, -C(=O)NH2, -C(=O)NHC1-C3 alkyl, -C(=O)N(C1-C3 alkyl)2, -P(=O)(C1-C3 alkyl)2, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl, C1-C3 heteroalkyl or C3-C6 cycloalkyl; Or two R atoms on the same atom form an oxo group; The condition is that if ring C is cyclopropyl, then ring B does not exist.

[0041] In some embodiments of the compound of formula (I), the compound is a compound of formula (Ia) or (Ib): Equation (Ia), Equation (Ib), Wherein the ring C is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, provided that the ring C is not a cyclopropyl group.

[0042] In some embodiments of the compound of formula (I), ring B is absent.

[0043] In some embodiments of the compound of formula (I), the compound is a compound of formula (Ic): Formula (Ic), The ring C is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group.

[0044] In some embodiments of the compound of formula (I), the compound is a compound of formula (Id): Formula (Id), Wherein the ring C is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, provided that the ring C is not a cyclopropyl group.

[0045] In some embodiments of compounds of formula (I) or (Ia)-(Id), X is -N-. In some embodiments, X is -CR X -

[0046] In some embodiments of compounds of formula (I) or (Ia)-(Id), R X It is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments, R X It is hydrogen, halogen, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, R X It is hydrogen, halogen, or C1-C6 alkyl. In some embodiments, R X It is hydrogen or halogen. In some embodiments, R X It is hydrogen.

[0047] In some embodiments of compounds of formula (I) or (Ia)-(Id), Y is -N- or -CR. Y - In some embodiments, Y is -N-. In some embodiments, Y is -CR. Y -

[0048] In some embodiments of compounds of formula (I) or (Ia)-(Id), R Y It is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments, R Y It is hydrogen, halogen, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, R Y It is hydrogen, halogen, or C1-C6 alkyl. In some embodiments, R Y It is hydrogen or halogen. In some embodiments, R Y It is hydrogen.

[0049] In some embodiments of compounds of formula (I) or (Ia)-(Id), X is -CR X -and Y is -CR Y - In some embodiments, X is -CH- and Y is -CH-.

[0050] In some embodiments of compounds of formula (I) or (Ia)-(Ic), L 1 It does not exist, or it is -O-, -S-, or -NR. 2 -、-C(R 3 )2-、-C(R 3 )2-C(R 3 )2-、-C(R 3 )=C(R 3 )-、-C(R 3 )2O-、-OC(R 3)2-、-C(R 3 )2S-、-SC(R 3 )2-、-C(R 3 )2NR 2 -or-NR 2 C(R 3 )2-.

[0051] In some embodiments of compounds of formula (I) or (Ia)-(Ic), L 1 It does not exist, or it is -O- or -C(R) 3 )2- or -C(R 3 )2O-. In some embodiments, L 1 It does not exist or is -O- or -C(R) 3 )2-. In some embodiments, L 1 Not present or -O-. In some embodiments, L 1 -O- or -C(R) 3 )2O-. In some embodiments, L 1 It does not exist. In some embodiments, L 1 For -O-. In some embodiments, L 1 -C(R) 3 )2-.

[0052] In some embodiments of compounds of formula (I), (Ia), or (Ic), L 2 It does not exist, or it is -O-, -S-, or -NR. 2 -、-C(R 3 )2-、-C(R 3 )2-C(R 3 )2-、-C(R 3 )=C(R 3 )-、-C(R 3 )2O-、-OC(R 3 )2-、-C(R 3 )2S-、-SC(R 3 )2-、-C(R 3 )2NR 2 -or-NR 2 C(R 3 )2-.

[0053] In some embodiments of compounds of formula (I), (Ia), or (Ic), L 2 Does not exist, or is -NR 2 -or C(R) 3 )2-. In some embodiments, L 2 Not present or -NR 2 -. In some embodiments, L2 It does not exist. In some embodiments, L 2 For -NR 2 -. In some embodiments, L 2 It is -NH-.

[0054] In some embodiments of compounds of formula (I) or (Ia)-(Ic), R 2 It is hydrogen, a C1-C6 alkyl group, or a C1-C6 haloalkyl group. In some embodiments, R 2 It is hydrogen or a C1-C6 alkyl group. In some embodiments, R 2 It is hydrogen.

[0055] In some embodiments of compounds of formula (I) or (Ia)-(Ic), each R 3 Independently, it is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, each R 3 Independently, it is hydrogen or C1-C6 alkyl. In some embodiments, each R 3 It is hydrogen.

[0056] In some embodiments of compounds of formula (I) or (Ia)-(Id), ring A is a cycloalkyl or heterocycloalkyl. In some embodiments, ring A is a cycloalkyl. In some embodiments, ring A is a fully saturated cycloalkyl. In some embodiments, ring A is a fully saturated C5-C6 monocycloalkyl, a fully saturated C7-C6 monocycloalkyl, or a fully saturated C7-C6 monocycloalkyl. 10 Spirocyclic cycloalkyl or fully saturated C 7- C 10 Bridged cycloalkyl. In some embodiments, ring A is a partially saturated cycloalkyl. In some embodiments, ring A is a partially saturated C5-C6 cycloalkyl. In some embodiments, ring A is a heterocyclic alkyl. In some embodiments, ring A is a monoheterocyclic alkyl, fused heterocyclic alkyl, spirocyclic heterocyclic alkyl, or bridged heterocyclic alkyl. In some embodiments, ring A is a 5- or 6-membered monoheterocyclic alkyl, a 7- to 10-membered spirocyclic heterocyclic alkyl, or a 7- to 10-membered bridged heterocyclic alkyl. In some embodiments, ring A is aryl or heteroaryl. In some embodiments, ring A is aryl. In some embodiments, ring A is phenyl. In some embodiments, ring A is heteroaryl. In some embodiments, ring A is a 5- or 6-membered heteroaryl. In some embodiments, ring A is pyridyl or pyrimidinyl.

[0057] In some embodiments of compounds of formula (I) or (Ia)-(Id), each R 1 Independently, it is halogen, -CN, -OH, -SF5, -OR a -NR c R d -C(=O)R a -C(=O)OR b-C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl); wherein each alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally separated by one or more R 1a Replacement. In some embodiments, each R 1 Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments, each R 1 Independently, it is halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, each R 1 Independently, it is halogen, -OR a C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, each R 1 Independently, it is a halogen, a C1-C6 alkyl group, or a C1-C6 haloalkyl group. In some embodiments, each R 1 Independently, it is a halogen or a C1-C6 haloalkyl group. In some embodiments, each R 1 Independently, each R is a C1-C6 haloalkyl group. In some embodiments, each R 1 Independently, it is a halogen. In some embodiments, each R 1 Independently, it is OCF3, -CF3, -CHF2, -F, -Cl, -SF5, methyl, ethyl, isopropyl, or n-propyl.

[0058] In some embodiments of compounds of formula (I) or (Ia)-(Id), each R 1a Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b-C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently and optionally substituted by one or more R; or two R on the same atom. 1a Together they form an oxygen. In some embodiments, each R... 1a Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, each R 1a Independently, it is halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, each R 1a It is independently a halogen, a C1-C6 alkyl, or a C1-C6 haloalkyl.

[0059] In some embodiments of compounds of formula (I) or (Ia)-(Id), n is 0, 1, 2, or 3. In some embodiments, n is 0, 1, or 2. In some embodiments, n is 0 or 1. In some embodiments, n is 1 or 2. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3.

[0060] In some embodiments of compounds of formula (I) or (Ia)-(Id), yes , , , , , , , , , , , , , or Each R 1aa Independently hydrogen or R1 .

[0061] In some embodiments of compounds of formula (I) or (Ia)-(Id), yes , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0062] In some embodiments of compounds of formula (I) or (Ia)-(Id), yes , , or In some embodiments, is In some embodiments, yes In some embodiments, yes In some embodiments, yes .

[0063] In some embodiments of compounds of formula (I), ring C is a cycloalkyl group, provided that ring B is absent when ring C is cyclopropyl. In some embodiments, ring C is a fully saturated cycloalkyl group, provided that ring C is not cyclopropyl. In some embodiments, ring C is a fully saturated C3-C6 monocycloalkyl group, a fully saturated C7-C6 monocycloalkyl group, or a fully saturated C7-C6 monocycloalkyl group. 10 Spirocyclic cycloalkyl or fully saturated C7-C 10 Bridged cycloalkyl, provided that ring C is cyclopropyl, then ring B does not exist.

[0064] In some embodiments of compounds of formula (Ia), (Ib), or (Id), the ring C is a cycloalkyl group, provided that the ring C is not a cyclopropyl group. In some embodiments, the ring C is a fully saturated cycloalkyl group, provided that the ring C is not a cyclopropyl group. In some embodiments, the ring C is a fully saturated C3-C6 monocycloalkyl group, a fully saturated C7-C6 monocycloalkyl group, or a fully saturated C7-C6 monocycloalkyl group. 10 Spirocyclic cycloalkyl or fully saturated C 7- C 10 Bridged cycloalkyl, provided that the ring carbon is not cyclopropyl.

[0065] In some embodiments of compounds of formula (Ic), the ring C is a cycloalkyl group. In some embodiments, the ring C is a fully saturated cycloalkyl group. In some embodiments, the ring C is a fully saturated C3-C6 monocycloalkyl group or a fully saturated C7-C6 monocycloalkyl group. 10 Spirocyclic cycloalkyl or fully saturated C 7- C 10 Bridged cycloalkyl group. In some embodiments, the ring C is cyclopropyl.

[0066] In some embodiments of compounds of formula (I) or (Ia)-(Id), ring C is a heterocyclic alkyl group. In some embodiments, ring C is a monoheterocyclic alkyl group, a fused heterocyclic alkyl group, a spirocyclic heterocyclic alkyl group, or a bridged heterocyclic alkyl group. In some embodiments, ring C is a 3- or 6-membered monoheterocyclic alkyl group, a 7- to 10-membered spirocyclic heterocyclic alkyl group, or a 7- to 10-membered bridged heterocyclic alkyl group. In some embodiments, ring C is a 4- or 6-membered monoheterocyclic alkyl group. In some embodiments, ring C is... , , , , , or .

[0067] In some embodiments of compounds of formula (I) or (Ia)-(Id), the ring C is aryl or heteroaryl. In some embodiments, the ring C is aryl. In some embodiments, the ring C is phenyl. In some embodiments, the ring C is heteroaryl. In some embodiments, the ring C is a 5- or 6-membered heteroaryl.

[0068] In some embodiments of the compound of formula (Ic), yes In some embodiments of the compound, yes In some embodiments of the compound, yes .

[0069] In some embodiments of the compound of formula (Ic), R 4 It is hydrogen or a C1-C6 alkyl group. In some embodiments, R4 It is hydrogen.

[0070] In some embodiments of the compound of formula (Ic), R 5 It is hydrogen or a C1-C6 alkyl group. In some embodiments, R 5 It is hydrogen.

[0071] In some embodiments of the compound of formula (Ic), R 6 It is hydrogen or a C1-C6 alkyl group. In some embodiments, R 6 It is hydrogen.

[0072] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 7 It is hydrogen, -OH, or a C1-C6 alkyl group. In some embodiments, R 7 It is hydrogen. In some embodiments, R 7 It is -OH.

[0073] In some embodiments of compounds of formula (I) or (Ia)-(Id), p is 0, 1, 2, 3, or 4. In some embodiments, p is 0, 1, 2, or 3. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4.

[0074] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 It is hydrogen, -C(=O)OR 9 -C(=O)NR 10 R 11 S(=O)2NR 10 R 11 -P(=O)(OR) 10 (OR) 11 ) or -B (OR 10 (OR) 11 ).

[0075] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 It is hydrogen, -C(=O)OR 9 -C(=O)NR 10 R 11 or -S(=O)2NR 10 R 11 In some embodiments, R 8 It is hydrogen. In some embodiments, R 8 It is -C(=O)OR 9 In some embodiments, R 8 It is -C(=O)NR 10R 11 In some embodiments, R 8 It is -S(=O)2NR 10 R 11 .

[0076] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 9 It is hydrogen, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally influenced by one or more R 9a Replacement. In some embodiments, R 9 It is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally separated by one or more R 9a Replacement. In some embodiments, R 9 It is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally influenced by one or more R 9a Replacement. In some embodiments, R 9 It is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, or heterocycloalkyl, wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently and optionally converted by one or more R 9a Replacement. In some embodiments, R 9 It is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments, R 9 It is hydrogen, a C1-C6 alkyl group, or a C1-C6 haloalkyl group. In some embodiments, R 9 It is hydrogen or a C1-C6 alkyl group. In some embodiments, R 9 It is hydrogen.

[0077] In some embodiments of compounds of formula (I) or (Ia)-(Id), each R 9aIndependently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently and optionally substituted by one or more R; or two R on the same atom. 9a Together they form an oxygen. In some embodiments, each R... 9a Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, each R 9a Independently, it is halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, each R 9a It is independently a halogen, a C1-C6 alkyl, or a C1-C6 haloalkyl.

[0078] In some embodiments of compounds of formula (I) or (Ia)-(Id), each R 10a Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c Rd -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R.

[0079] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 and R 11 Each of the following is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally influenced by one or more R 10a replace.

[0080] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 and R 11 Each of the following is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally influenced by one or more R 10a Replacement. In some embodiments, R 10 and R 11Each of the following is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, aryl, and heteroaryl group is independently and optionally influenced by one or more R 10a Replacement. In some embodiments, R 10 and R 11 Each is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, R 10 and R 11 Each is independently hydrogen, C1-C6 alkyl, C1-C6 hydroxyalkyl, or C1-C6 heteroalkyl. In some embodiments, R 10 and R 11 Each is independently hydrogen or C1-C6 alkyl. In some embodiments, R 10 and R 11 Each is independently hydrogen or optionally composed of one or more R 10a Substituted heterocyclic alkyl groups.

[0081] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 It is hydrogen and R 11 It is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl group is independently and optionally influenced by one or more R 10a replace.

[0082] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 It is hydrogen and R 11 It is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, heterocycloalkyl, C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, aryl, and heteroaryl group is independently and optionally marked by one or more R 10a replace.

[0083] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 It is hydrogen and R 11It is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl or heterocyclic alkyl, wherein each alkyl and heterocyclic alkyl is independently and optionally marked by one or more R 10a replace.

[0084] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 It is hydrogen and R 11 It is a C1-C6 alkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl or heterocyclic alkyl, wherein each alkyl and heterocyclic alkyl group is independently and optionally influenced by one or more R groups. 10a replace.

[0085] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 It is hydrogen and R 11 It is optionally controlled by one or more R 10a Substituted heterocyclic alkyl groups.

[0086] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 It is hydrogen and R 11 It is optionally controlled by one or more R 10a Substituted monocyclic heterocyclic alkyl groups.

[0087] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 It is hydrogen and R 11 It is optionally controlled by one or more R 10a Substituted bicyclic heterocyclic alkyl groups. In some embodiments, R 10 It is hydrogen and R 11 It is optionally controlled by one or more R 10a Substituted fused bicyclic heterocyclic alkyl groups. In some embodiments, R 10 It is hydrogen and R 11 It is optionally controlled by one or more R 10a Substituted bridged bicyclic heterocyclic alkyl groups. In some embodiments, R 10 It is hydrogen and R 11 It is optionally controlled by one or more R 10a Substituted bicyclic spirocyclic heterocyclic alkyl groups.

[0088] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 It is hydrogen and R 11 yes or Each of them is optionally controlled by one or more R 10a replace.

[0089] In some embodiments of compounds of formula (I) or (Ia)-(Id), each R 10a Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently and optionally substituted by one or more R; or two R on the same atom. 10a Together they form an oxygen. In some embodiments, each R... 10a Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, each R 10a Independently, it is halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, each R 10a Independently, it is a halogen, a C1-C6 alkyl group, or a C1-C6 haloalkyl group. In some embodiments, each R 10a Independently, it is halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, each R 10a Independently, it is halogen, -OH, -OR a C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, each R 10a Independently, it is a halogen, -OH, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, each R 10a Independently, it is -OH, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, each R 10aIt is -OH on its own.

[0090] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 and R 11 Together with the atoms they are attached to, they form a group optionally bounded by one or more R atoms. 10b Substituted heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted monocyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted 4- to 6-membered monocyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted bicyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted 5- to 12-membered bicyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted fused bicyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted 5- to 12-membered fused bicyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted bridged bicyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted 5- to 12-membered bridged bicyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted 6- to 8-membered bridged bicyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Substituted bicyclic spirocyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Replaced by 5- to 12-membered bicyclic spirocyclic heterocyclic alkyl groups. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form heterocyclic alkyl groups, wherein the heterocyclic alkyl groups contain 1-2 nitrogen atoms and 0-1 oxygen atoms. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form heterocyclic alkyl groups, wherein the heterocyclic alkyl group contains one nitrogen atom.

[0091] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 and R 11 Together with the atoms they are attached to, they form , , , Each of them is optionally controlled by one or more (e.g., one, two, or three) R 10b replace.

[0092] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Replacement .

[0093] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 and R 11 Together with the atoms they are attached to, they form , , , , , , or Each of them is optionally controlled by one or more (e.g., one, two, or three) R 10bSubstitution. In some embodiments of compounds of formula (I) or (Ia)-(Id), R 10 and R 11 Together with the atoms they are attached to, they form , , , , , or Each of them is optionally controlled by one or more (e.g., one, two, or three) R 10b Replacement. In some embodiments, R 10 and R 11 Together with the atoms they are attached to, they form an array optionally composed of one or more (e.g., one, two, or three) R atoms. 10b Replacement .

[0094] In some embodiments of compounds of formula (I) or (Ia)-(Id), each R 10b Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently and optionally substituted by one or more R; or two R on the same atom. 10b Together they form an oxygen. In some embodiments, each R... 10b Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, each R 10b Independently, it is halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some embodiments, each R10b Independently, it is a halogen, a C1-C6 alkyl group, or a C1-C6 haloalkyl group. In some embodiments, each R 10b Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl or C1-C6 haloalkyl. In some embodiments, each R 10b Independently -CN, -OH, -OR a or -NR c R d In some embodiments, each R 10b Independently, it is -CN. In some embodiments, each R 10b It is -OH on its own.

[0095] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 It is hydrogen.

[0096] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 yes , , , , , , , , , , , , , , , , , , , or .

[0097] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 yes , , , , , , , , , or .

[0098] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 yes , , , , , , , , , , , , , , , , , , or .

[0099] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 yes or .

[0100] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 yes , , , , , , , , , or .

[0101] In some embodiments of compounds of formula (I) or (Ia)-(Id), R 8 yes , , or .

[0102] In some embodiments of compounds of formula (I) or (Ia)-(Id), yes , , , , , , , , , or .

[0103] In some embodiments of compounds of formula (I), (Ia), (Ib), or (Id), ring B is phenyl, and both U and T are -C-. In some embodiments, ring B is a 6-membered heteroaryl, and both U and T are -C-.

[0104] In some embodiments of compounds of formula (I), (Ia), (Ib) or (Id), ring B is phenyl, 5- or 6-membered heteroaryl, or 5-membered heterocyclic alkyl.

[0105] In some embodiments of compounds of formula (I), (Ia), (Ib), or (Id), ring B is a 5-membered heteroaryl, 6-membered heteroaryl, 5-membered heterocycloalkyl, 6-membered heterocycloalkyl, cyclopentyl, or cyclohexyl. In some embodiments, ring B is a 5-membered heteroaryl or 5-membered heterocycloalkyl. In some embodiments, ring B is phenyl. In some embodiments, ring B is a 5-membered or 6-membered heteroaryl. In some embodiments, ring B is a 5-membered heteroaryl. In some embodiments, ring B is pyrroloyl, furanyl, thiophene, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, or triazolyl. In some embodiments, ring B is imidazolyl, pyrazolyl, thiazolyl, or oxazolyl. In some embodiments, ring B is pyrazolyl. In some embodiments, ring B is a 6-membered heteroaryl. In some embodiments, ring B is pyridinyl, pyrimidinyl, or pyrazinyl. In some embodiments, ring B is pyridinyl. In some embodiments, ring B is a 5-membered heterocycloalkyl.

[0106] In some embodiments of compounds of formula (I) or (Ia)-(Id), each R 12 Independently, it is halogen, -CN, -OH, -OR a -NR c R d -C(=O)R a -C(=O)OR b -C(=O)NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl group is optionally and independently substituted by one or more R. In some embodiments, each R 12 Independently, it is halogen, -CN, -OH, -OR a -NR c R dC1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl group is optionally and independently substituted by one or more R. In some embodiments, each R 12 Independently, it is a halogen, -CN, -OH, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl, or heterocycloalkyl. In some embodiments, each R 12 Independently, it is phenyl. In some embodiments, each R 12 Independently, it is a 5- or 6-membered heteroaryl group. In some embodiments, each R 12 Independently, each R is a C3-C6 cycloalkyl group. In some embodiments, each R 12 Independently, each R is a 5- or 6-membered heterocyclic alkyl group. In some embodiments, each R 12 Independently, it is -CN, C1-C6 alkyl, or C1-C6 haloalkyl. In some embodiments, each R 12 Independently, each R is a C1-C6 alkyl group. In some embodiments, each R 12 It is independently -CN, methyl, -CHF2, cyclopropyl, or pyridyl. In some embodiments, the methyl group is -CD3.

[0107] In some embodiments of compounds of formula (I) or (Ia)-(Id), m is 0 or 1. In some embodiments, m is 1 or 2. In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3.

[0108] In some embodiments of compounds of formula (I), (Ia), (Ib), or (Id), yes , , , , , , , , , , , , , , , , , , or Each R 12aa Independently hydrogen or R 12 In some embodiments, yes , , , , , , , , Each R 12aa Independently hydrogen or R 12 In some embodiments, yes , or Each R 12aa Independently hydrogen or R 12 .

[0109] In some embodiments of compounds of formula (I), (Ia), (Ib), or (Id), yes , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0110] In some embodiments of compounds of formula (I), (Ia), (Ib), or (Id), yes or .

[0111] In some embodiments of compounds of formula (I), (Ia), (Ib), or (Id), yes , , or .

[0112] In some embodiments of the compound of formula (I), yes .

[0113] In some embodiments of the compounds disclosed herein, each R a Independently, each of the following is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally substituted by one or more R. In some embodiments of the compounds disclosed herein, each R a Independently, each of the following is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl group is optionally substituted by one or more Rs. In some embodiments of the compounds disclosed herein, each R... a Independently, each of the following is a C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted by one or more Rs. In some embodiments of the compounds disclosed herein, each R... a Independently, each R is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl. In some examples of the compounds disclosed herein, each R a Independently, each R is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some examples of the compounds disclosed herein, each R a Independently, it is a C1-C6 alkyl or a C1-C6 haloalkyl. In some examples of the compounds disclosed herein, each R a It is independently a C1-C6 alkyl group.

[0114] In some embodiments of the compounds disclosed herein, each R b Independently, each of the following is a hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally substituted by one or more R. In some embodiments of the compounds disclosed herein, each R bIndependently, each alkyl group is hydrogen, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 hydroxyalkyl group, a C1-C6 aminoalkyl group, a C1-C6 heteroalkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, wherein each alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group, and heteroaryl group is optionally substituted by one or more R groups. In some embodiments of the compounds disclosed herein, each R group is... b Independently, it is hydrogen, a C1-C6 alkylene (cycloalkyl), a C1-C6 alkylene (heterocycloalkyl), a C1-C6 alkylene (aryl), or a C1-C6 alkylene (heteroaryl), wherein each alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally substituted by one or more R. In some embodiments of the compounds disclosed herein, each R b Independently, it is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl. In some examples of the compounds disclosed herein, each R... b Independently, it is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some examples of the compounds disclosed herein, each R... b Independently, it is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl. In some examples of the compounds disclosed herein, each R... b Independently, it is hydrogen or C1-C6 alkyl. In some examples of the compounds disclosed herein, each R... b It is hydrogen. In some embodiments of the compounds disclosed herein, each R b It is independently a C1-C6 alkyl group.

[0115] In some embodiments of the compounds disclosed herein, R c and R d Each of the following is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted by one or more R. In some embodiments of the compounds disclosed herein, R c and R dEach of the following is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted by one or more R. In some embodiments of the compounds disclosed herein, each R b Independently, it is hydrogen, a C1-C6 alkylene (cycloalkyl), a C1-C6 alkylene (heterocycloalkyl), a C1-C6 alkylene (aryl), or a C1-C6 alkylene (heteroaryl), wherein each alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally substituted by one or more R. In some embodiments of the compounds disclosed herein, R c and R d Each is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, cycloalkyl, or heterocycloalkyl. In some examples of the compounds disclosed herein, R c and R d Each is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, or C1-C6 heteroalkyl. In some examples of the compounds disclosed herein, R c and R d Each is independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl. In some examples of the compounds disclosed herein, R c and R d Each is independently hydrogen or C1-C6 alkyl. In some embodiments of the compounds disclosed herein, R c and R d Each is hydrogen. In some embodiments of the compounds disclosed herein, R c and R d Each is independently a C1-C6 alkyl group.

[0116] In some embodiments of the compounds disclosed herein, R c and R d Together with the atoms to which they are attached, they form heterocyclic alkyl groups that are optionally substituted with one or more R atoms.

[0117] In some embodiments of the compounds disclosed herein, each R is independently a halogen, -CN, -OH, -SF5, -NH2, -NHC1-C3 alkyl, -N(C1-C3 alkyl)2, -C(=O)C1-C3 alkyl, -C(=O)OH, -C(=O)OC1-C3 alkyl, -C(=O)NH2, -C(=O)NHC1-C3 alkyl, -C(=O)N(C1-C3 alkyl)2, -P(=O)(C1-C3 alkyl)2, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl, C1-C3 heteroalkyl, or C3-C6 cycloalkyl; or two Rs on the same atom form an oxo group. In some embodiments of the compounds disclosed herein, each R is independently a halogen, -CN, -OH, -SF5, -NH2, -NHC1-C3 alkyl, -N(C1-C3 alkyl)2, -P(=O)(C1-C3 alkyl)2, C1-C3 alkyl, C1-C3 alkoxy, or C1-C3 haloalkyl; or two Rs on the same atom form an oxo group. In some embodiments of the compounds disclosed herein, each R is independently a halogen, -CN, -OH, -NH2, C1-C3 alkyl, or C1-C3 haloalkyl; or two Rs on the same atom form an oxo group. In some embodiments of the compounds disclosed herein, each R is independently a halogen, C1-C3 alkyl, or C1-C3 haloalkyl; or two Rs on the same atom form an oxo group.

[0118] In some embodiments of the compounds disclosed herein, R, R 1 R 1a R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 9a R 10 R 10a R 10b R 11 R 12 R 13 R 14 R 15 R 16 R 17 R 18 R 19 R X R Y R a R b R c and R dOne or more of the groups contain deuterium in a percentage higher than the natural abundance of deuterium.

[0119] In some embodiments of the compounds disclosed herein, the following groups R, R 1 R 1a R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 9a R 10 R 10a R 10b R 11 R 12 R 13 R 14 R 15 R 16 R 17 R 18 R 19 R X R Y R a R b R c and R d One or more of them, one or more of them 1 H is replaced by one or more deuterium atoms.

[0120] In some embodiments of the compounds disclosed herein, R, R 1 R 1a R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 9a R 10 R 10a R 10b R 11 R 12 R 13 R 14 R 15 R 16 R 17 R 18 R 19 R X R Y R a R b Rc and R d The abundance of each of the intermediate deuterium is independently at least 1%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% by molar weight.

[0121] In some embodiments of the compounds disclosed herein, one or more of ring A or ring B 1 H is replaced by one or more deuterium atoms.

[0122] This document considers any combination of the aforementioned groups for each variable. Throughout the specification, the groups and their substituents were selected by those skilled in the art to provide stable moieties and compounds.

[0123] In some embodiments, the compounds disclosed herein or their pharmaceutically acceptable salts or stereoisomers are one of the compounds listed in Table 1. Table 1

[0124] In some embodiments, the compounds disclosed herein or their pharmaceutically acceptable salts or stereoisomers are one of the compounds listed in Table 2. Table 2 Other forms of the compounds disclosed in this article Isomers / stereoisomers

[0125] In some embodiments, the compounds described herein exist as geometric isomers. In some embodiments, the compounds described herein have one or more double bonds. The compounds presented herein include all cis, trans, syn, anti, E (entgegen, E), and Z (zusammen, Z) isomers, and corresponding mixtures thereof. In some cases, the compounds described herein have one or more chiral centers, each center existing in an R or S configuration. The compounds described herein include all diastereomeric, enantiomeric, and epimeric forms, and corresponding mixtures thereof. In further embodiments of the compounds and methods provided herein, mixtures of enantiomers and / or diastereomeric compounds produced by a single preparation step, combination, or tautomerization can be used for the applications described herein. In some embodiments, the compounds described herein are prepared as separate stereoisomers by reacting a racemic mixture of the compounds with an optically active resolving agent to form a pair of diastereomeric compounds, separating the diastereomeric compounds, and recovering the optically pure enantiomers. In some embodiments, dissociable complexes are preferred. In some embodiments, diastereomers have different physical properties (e.g., melting point, boiling point, solubility, reactivity, etc.) and are separated by utilizing these differences. In some embodiments, diastereomers are separated by chiral chromatography, or preferably by a separation / resolution technique based on solubility differences. In some embodiments, the optically pure enantiomers, along with the resolving agent, are then recovered by any practical means that does not cause racemization.

[0126] Unless otherwise stated, in this disclosure, the solid wedge ( ) and virtual wedge line ( The bond, represented by a solid line, is used to indicate the absolute configuration of the chiral center. ) and dashed lines ( The bond, represented by ) is used to indicate the relative configuration of the chiral center, and is indicated by wavy lines ( The key indicated by ) is used to indicate (1) solid wedge ( ) or virtual wedge ( ), or (2) solid line ( ) or dashed line ( ). Isotope enrichment compounds

[0127] Unless otherwise stated, the compounds described herein may exhibit their natural isotopic abundance, or one or more of the atoms may be artificially enriched with a specific isotope that has the same atomic number but an atomic mass or mass number different from the atomic mass or mass number predominantly found in nature. All isotopic variants of the compounds of the present disclosure, whether radioactive or not, are encompassed within the scope of the present disclosure. For example, hydrogen has three naturally occurring isotopes, denoted as 1 H (protium), 2 H (deuterium) and 3 H (tritium). Protium is the most abundant isotope of hydrogen in nature. Enrichment with deuterium can provide certain therapeutic advantages, such as increased in vivo half-life and / or exposure, or can provide compounds that can be used to study in vivo pathways of drug elimination and metabolism.

[0128] For example, the compounds described herein may be artificially enriched with one or more specific isotopes. In some embodiments, the compounds described herein may be artificially enriched with one or more isotopes that are not predominantly found in nature. In some embodiments, the compounds described herein may be artificially enriched with one or more isotopes selected from deuterium ( 2 H), tritium ( 3 H), iodine-125 ( 125 I) or carbon-14 ( 14 C). In some embodiments, the compounds described herein are artificially enriched with one or more selected from 2 H, 11 C, 13 C, 14 C, 15 C, 12 N, 13 N, 15 N, 16 N, 16 O, 17 O, 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl, 37 Cl, 79 Br, 81 Br, 131 I and 125Isotopes of I. In some embodiments, the abundance of the enriched isotopes is independently at least 1%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100% on a molar basis.

[0129] In some embodiments, the compound is deuterated at at least one position. In some embodiments, some or all of the compounds disclosed herein 1 H atoms are 2 H atom substitution.

[0130] Methods for synthesizing deuterium-containing compounds are known in the art, and include only the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997 and the following synthetic methods by way of non-limiting example only. For example, deuterium-substituted compounds can be synthesized using a variety of methods, as described below: Dean, Dennis C., ed. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In Curr., Pharm. Des., 2000; 6(10)] 2000, p. 110; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0131] Deuterated starting materials are readily available and can be synthesized using the methods described herein to provide the synthesis of deuterium-containing compounds. A wide range of deuterium-containing reagents and building blocks are commercially available from chemical suppliers such as Aldrich Chemical Co. Pharmaceutically acceptable salts

[0132] In some embodiments, the compounds described herein are present as pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating a disease by administering such pharmaceutically acceptable salts. In some embodiments, the methods disclosed herein include methods of treating a disease by administering such pharmaceutically acceptable salts as a pharmaceutical composition.

[0133] In some embodiments, the compounds described herein have acidic or basic groups and thus react with a variety of inorganic or organic bases and any of inorganic and organic acids to form pharmaceutically acceptable salts. In some embodiments, these salts are prepared in situ during the final isolation and purification of the compounds disclosed herein or their stereoisomers, or by reacting the purified compounds in their free form alone with a suitable acid or base and isolating the resulting salts.

[0134] Examples of pharmaceutically acceptable salts include those prepared by reacting the compounds described herein with minerals, organic acids, or inorganic bases. These salts include: acetates, acrylates, adipates, alginates, aspartates, benzoates, benzenesulfonates, bisulfates, bisulfites, bromides, butyrates, butyn-1,4-dicitates, camphorates, camphorsulfonates, hexanoates, octanoates, chlorobenzoates, chlorides, citrates, cyclopentanepropionates, decanoates, disglucurons, dihydrogen phosphates, dinitrobenzoates, dodecyl sulfates, ethanesulfonates, formates, fumarates, glucono-2-phosphates, glycerophosphates, glycolates, hemisulfates, heptahydrates, hexyn-1,6-dicitates, hydroxybenzoates, and gamma-hydroxybutyrates. Salts, hydrochlorides, hydrobromides, hydroiodates, 2-hydroxyethanesulfonates, iodides, isobutyrates, lactates, maleates, malonates, methanesulfonates, mandelates, metaphosphates, methanesulfonates, methoxybenzoates, methylbenzoates, hydrogen phosphates, 1-naphthalenesulfonates, 2-naphthalenesulfonates, nicotinates, nitrates, palmitates, pectinates, persulfates, 3-phenylpropionates, phosphates, picrates, neopentanoates, propionates, pyrosulfates, pyrophosphates, propynates, phthalates, phenylacetates, phenylbutyrates, propanesulfonates, salicylates, succinates, sulfates, sulfites, succinates, octanoates, sebacic acid salts, sulfonates, tartrates, thiocyanates, toluenesulfonates, undecanoates, and xylenesulfonates.

[0135] Furthermore, the compounds described herein can be prepared as pharmaceutically acceptable salts, which are formed by reacting the free base form of the compounds with pharmaceutically acceptable inorganic or organic acids, including but not limited to inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, metaphosphoric acid, etc.; and organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, p-toluenesulfonic acid, tartaric acid, trifluoroacetic acid, citric acid, benzoic acid, etc. Acids, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, arylsulfonic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2-naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-en-1-carboxylic acid, glucoheponic acid, 4,4'-methylenebis-(3-hydroxy-2-en-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, dodecyl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and mucoconic acid. In some embodiments, other acids, such as oxalic acid, although not pharmaceutically acceptable on their own, are used to prepare salts that can be used as intermediates in obtaining the compounds disclosed herein or their stereoisomers and their pharmaceutically acceptable acid addition salts.

[0136] In some embodiments, those compounds comprising free acid groups described herein react with suitable bases (such as hydroxides, carbonates, bicarbonates, and sulfates of pharmaceutically acceptable metal cations), with ammonia, or with pharmaceutically acceptable primary, secondary, tertiary, or quaternary organic amines. Representative salts include alkali metal or alkaline earth metal salts, such as lithium, sodium, potassium, calcium, and magnesium salts, as well as aluminum salts. Illustrative examples of bases include sodium hydroxide, potassium hydroxide, choline hydroxide, sodium carbonate, and N2SO4. + (C 1-4 Alkyl)4, etc.

[0137] Representative organic amines that can be used to form base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, etc. It should be understood that the compounds described herein also include quaternization of any basic nitrogen-containing groups they contain. In some embodiments, water-soluble or oil-soluble or dispersible products are obtained via such quaternization. solvates

[0138] In some embodiments, the compounds described herein are present as solvates. The present invention provides a method for treating a disease by applying such solvates. The present invention further provides a method for treating a disease by applying such solvates as pharmaceutical compositions.

[0139] The solvates contain stoichiometric or non-stoichiometric amounts of solvent and, in some embodiments, form with pharmaceutically acceptable solvents such as water, ethanol, etc. When the solvent is water, a hydrate is formed, or when the solvent is an alcohol, an alcohol is formed. The solvates of the compounds described herein can be readily prepared or formed during the methods described herein. By way of example only, the hydrates of the compounds described herein can be readily prepared from aqueous / organic solvent mixtures using organic solvents including, but not limited to, dioxane, tetrahydrofuran, or methanol. Furthermore, the compounds provided herein can exist in both unsolvated and solvated forms. Generally, for the purposes of the compounds and methods provided herein, the solvated form is considered equivalent to the unsolvated form. tautomer

[0140] In some cases, compounds exist as tautomers. The compounds described herein include all possible tautomers within the formulas described herein. Tautomers are compounds that can interconvert through hydrogen atom migration accompanied by the conversion of single bonds to adjacent double bonds. A chemical equilibrium of tautomers will exist within the possible tautomer bond arrangements. All tautomer forms of the compounds disclosed herein are considered. The precise ratio of tautomers depends on several factors, including temperature, solvent, and pH. Treatment

[0141] This article discloses a method for treating a disease in a subject in need, comprising administering to the subject an effective amount of the TEAD inhibitor described herein, or a pharmaceutically acceptable salt or stereoisomer thereof, or a composition described herein.

[0142] In some embodiments, the disease is mediated by TEAD activity.

[0143] In some embodiments, the disease is an advanced solid tumor. In some embodiments, the disease is a solid tumor. In some embodiments, the disease is cancer or a proliferative condition. In some embodiments, cancer is associated with increased TEAD expression. In some embodiments, cancer is associated with increased TEAD activity.

[0144] In some embodiments, cancer is cancer in which YAP is located in the nucleus of cancer cells.

[0145] In some embodiments, increased TEAD expression or activity is due to increased TEAD1 expression or activity. In some embodiments, increased TEAD expression or activity is due to increased TEAD2 expression or activity. In some embodiments, increased TEAD expression or activity is due to increased TEAD3 expression or activity. In some embodiments, increased TEAD expression or activity is due to increased TEAD4 expression or activity.

[0146] In some embodiments, the diseases are acoustic neuroma, acute leukemia, acute lymphoblastic leukemia, acute myeloid leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchial cancer, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myeloid (granulocytic) leukemia, chronic myeloid leukemia, and colon cancer. Colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, proliferative dysplasia (dysplasia and metaplasia), embryonal carcinoma, endometrial cancer, endothelial sarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen receptor-positive breast cancer, essential thrombocytosis, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hemangioendothelioma, hepatocellular carcinoma, hormone-insensitive prostate cancer, smooth muscle cells. Myoma, leukemia, liposarcoma, lung cancer, lymphangiosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignant tumors and hyperproliferative disorders of the bladder, breast, colon, lung, ovary, pancreas, prostate, skin and uterus, T-cell or B-cell-derived malignant tumors of the lymphatic system, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myeloid leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC) Non-small cell lung cancer, oligodendroglioma, oral cancer, osteosarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinoma, papillary carcinoma, pineal tumor, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung cancer, solid tumors (carcinoma and sarcoma), small cell lung cancer, gastric cancer, squamous cell carcinoma, synovial tumor, sweat gland carcinoma, thyroid cancer, Waldenström macroglobulinemia, testicular tumor, uterine cancer, or Wilms' tumor.

[0147] This article also discloses a method for treating cancer in a subject in need, comprising administering to the subject in need an effective amount of the compound disclosed herein, or a pharmaceutically acceptable salt or stereoisomer thereof, or a pharmaceutical composition disclosed herein.

[0148] In some embodiments of the method for treating cancer, the cancer is mesothelioma. In some embodiments of the method for treating cancer, the cancer is NF2-deficient mesothelioma.

[0149] In some embodiments of methods for treating cancer, the cancer is epithelioid hemangioendothelioma.

[0150] In some embodiments of methods for treating cancer, the cancer is a liquid tumor. In some embodiments of methods for treating cancer, the cancer is a solid tumor.

[0151] The method of claim 222, wherein the solid tumor has an NF2 mutation, a LATS1 mutation, a LATS2 mutation, or any combination thereof. In some embodiments of the method for treating cancer, the solid tumor has an NF2 mutation. In some embodiments of the method for treating cancer, the solid tumor has a LATS1 mutation. In some embodiments of the method for treating cancer, the solid tumor has a LATS2 mutation. In some embodiments of the method for treating cancer, the solid tumor has a YAP1 / TAZ gene fusion.

[0152] In some embodiments, the disease is a fibrotic disease.

[0153] In some embodiments, fibrotic diseases include conditions related to fibrosis, lung fibrosis, idiopathic pulmonary fibrosis, renal fibrosis, cardiac fibrosis, skin fibrosis, systemic sclerosis, scleroderma, keloids or keloid scars, liver fibrosis, cirrhosis, diabetic retinopathy, intestinal fibrosis, cystic fibrosis, prostatic fibrosis, muscle fibrosis, pancreatic fibrosis, proliferative scars, localized scleroderma, fibrosis due to graft-versus-host disease, subepithelial fibrosis, endocardial myocardial fibrosis, uterine fibrosis, myelofibrosis, retroperitoneal fibrosis, renal systemic fibrosis, postoperative scarring, and asthma. Asthma, fibrosis due to abnormal wound healing, glomerulonephritis, endometriosis, multifocal fibrosis, radiation-induced fibrosis, radiation-induced pneumonia or radiation-induced pulmonary fibrosis; chemotherapy-induced or drug-induced fibrosis, fibrosis due to autoimmune diseases, lupus, intratumoral and cancer-related fibrosis / fibrosis, organ fibrosis after chronic inflammation, chronic kidney disease, organ fibrosis during long-term dialysis or end-stage diabetes, atrial fibrosis, glial scars, joint fibrosis, Crohn's disease, Dupuytren's contracture, mediastinal fibrosis, Peroni disease, progressive massive fibrosis or adhesive capsulitis.

[0154] This article also discloses a method for treating a subject in need of a disease in which Hippo pathway inhibition is beneficial, the method comprising administering to the subject in need an effective amount of the compound disclosed herein, or a pharmaceutically acceptable salt or stereoisomer thereof, or a pharmaceutical composition disclosed herein. Dosage

[0155] In some embodiments, a composition containing the compounds described herein is administered for therapeutic treatment. In some therapeutic applications, the composition is administered to a patient with a disease or ailment in an amount sufficient to cure or at least partially suppress at least one symptom of the disease or ailment. The effective amount for this purpose depends on the severity and course of the disease or ailment, prior treatment, the patient's health status, weight, and response to the drug, as well as the judgment of the attending physician. The therapeutically effective amount may optionally be determined by methods including, but not limited to, dose escalation and / or dose range clinical trials.

[0156] In some embodiments where the patient’s condition does not improve, the compound is administered long-term, i.e., for an extended period of time, including the patient’s entire lifespan, in accordance with the physician’s judgment, to improve or otherwise control or limit the symptoms of the patient’s disease or ailment.

[0157] Once the patient's condition improves, a maintenance dose may be administered if necessary. Subsequently, in specific embodiments, the dose or frequency of administration, or both, may be reduced according to symptoms.

[0158] The amount of a given agent corresponding to this quantity varies depending on factors such as the specific compound, the disease condition and its severity, and the characteristics of the subject or host requiring treatment (e.g., weight, sex), but is still determined based on the specific circumstances of the case, including, for example, the specific agent administered, the route of administration, the disease being treated, and the subject or host being treated.

[0159] In some embodiments, the dosage for adult treatment is typically in the range of 0.01 mg to 5000 mg per day. In some embodiments, the daily dose suitable for the compounds described herein or pharmaceutically acceptable salts thereof is about 0.01 to about 50 mg / kg body weight. In various embodiments, the daily dose and unit dose vary according to a number of variables, including but not limited to the activity of the compound used, the disease or ailment to be treated, the mode of administration, the individual subject's needs, the severity of the disease or ailment being treated, and the judgment of a practicing physician. Application route

[0160] Suitable routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, ocular, pulmonary, transmucosal, transdermal, vaginal, ear, nasal, and topical administration. Furthermore, by way of example only, parenteral delivery includes intramuscular, subcutaneous, intravenous, intramedullary injection, as well as intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injection.

[0161] In some embodiments, the compounds described herein are administered locally rather than systemically, such as by direct injection into an organ, typically as a reservoir formulation or a sustained-release formulation. In specific embodiments, long-acting formulations are administered via implantation (e.g., subcutaneously or intramuscularly) or by intramuscular injection. Furthermore, in other embodiments, the drug is delivered in a targeted drug delivery system, such as in liposomes coated with organ-specific antibodies. In such embodiments, the liposomes are targeted to the organ and selectively taken up by the organ. In yet another embodiment, the compounds described herein are provided in immediate-release, sustained-release, or intermediate-release formulations. Pharmaceutical Compositions / Formulations

[0162] In accordance with standard pharmaceutical practice, the compounds described herein are administered, in the form of a pharmaceutical composition, alone or in combination with a pharmaceutically acceptable carrier, excipient, or diluent to a subject of need. In some embodiments, the compounds described herein are administered to animals.

[0163] On the other hand, this document provides pharmaceutical compositions comprising the compounds described herein, or pharmaceutically acceptable salts or stereoisomers thereof, and at least one pharmaceutically acceptable excipient. The pharmaceutical compositions are formulated in a conventional manner using one or more pharmaceutically acceptable excipients that facilitate the processing of the active compound into a pharmaceutically acceptable formulation. A suitable formulation depends on the chosen route of administration. Summary of the pharmaceutical compositions described herein can be found in, for example, Remington: The Science and Practice of Pharmacy, 19th edition (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, HA and Lachman, L. (eds.), Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th edition (Lippincott Williams and Wilkins 1999), such disclosures being incorporated herein by reference.

[0164] In some embodiments, pharmaceutically acceptable excipients are selected from carriers, binders, fillers, suspending agents, flavoring agents, sweeteners, disintegrants, dispersants, surfactants, lubricants, colorants, diluents, solubilizers, humectants, plasticizers, stabilizers, penetration enhancers, wetting agents, antifoaming agents, antioxidants, preservatives, and any combination thereof.

[0165] The pharmaceutical formulations described herein include, but are not limited to, aqueous liquid dispersions, liquids, gels, syrups, elixirs, slurries, suspensions, self-emulsifying dispersions, solid solutions, liposome dispersions, aerosols, solid oral dosage forms, powders, immediate-release formulations, controlled-release formulations, rapidly melting formulations, tablets, capsules, pills, powders, sugar-coated pills, effervescent formulations, lyophilized formulations, delayed-release formulations, sustained-release formulations, pulsatile-release formulations, multi-particle formulations, and mixtures of immediate-release and controlled-release formulations. combination

[0166] This article discloses methods for treating diseases or conditions associated with TEAD using the compounds disclosed herein or their pharmaceutically acceptable salts or stereoisomers in combination with other therapeutic agents.

[0167] In some embodiments, an additional therapeutic agent is administered concurrently with the compounds disclosed herein. In some embodiments, the additional therapeutic agent and the compounds disclosed herein are administered sequentially. In some embodiments, the additional therapeutic agent is administered at a lower frequency than the compounds disclosed herein. In some embodiments, the additional therapeutic agent is administered at a higher frequency than the compounds disclosed herein. In some embodiments, the additional therapeutic agent is administered before the administration of the compounds disclosed herein. In some embodiments, the additional therapeutic agent is administered after the administration of the compounds disclosed herein.

[0168] In some embodiments, the additional therapeutic agent is an anticancer agent. Example

[0169] The following examples are provided to illustrate, rather than limit, the claimed invention. These examples further illustrate the invention, but should not be construed as limiting its scope in any way.

[0170] The following synthetic schemes are provided for illustrative purposes and not for limitation. The following examples illustrate various methods for preparing the compounds described herein. It should be understood that those skilled in the art may be able to prepare these compounds by similar methods or by combining other methods known to them. It should also be understood that those skilled in the art will be able to prepare them in a manner similar to that described below, by using appropriate starting materials and modifying the synthetic route as needed. Typically, starting materials and reagents are available from commercial suppliers, synthesized from sources known to those skilled in the art, or prepared as described herein. Example A: Synthesis of compounds 1, 2 and 3 Step 1: Preparation of 3-2

[0171] NaH (1.94 g, 48.5 mmol, 60% purity) was added to a solution of 3-1 (9.80 g, 40.49 mmol) in THF (10 mL) at 0°C. The reaction mixture was heated to 25°C and stirred for 30 min, then cooled to 0°C and SEM-Cl (8.10 g, 48.5 mmol, 8.60, 1.20 equivalents) was added, followed by stirring at 25°C for 3 h. The reaction mixture was filtered, poured into H2O (200 mL), extracted with ethyl acetate (40 mL × 5), washed with brine (60 mL × 2), dried over Na2SO4, filtered, concentrated, and purified by column chromatography to give 3-2 (13.0 g, 34.9 mmol, 86.2% yield). LCMS: 315.9 [M-55] + ; Step 2: Preparation of 3-3

[0172] Fe (4.20 g, 75.2 mmol) was added in three portions to a mixture of 3-2 (4.00 g, 10.7 mmol) and NH4Cl (4.02 g, 75.2 mmol) in EtOH (15 mL) and H2O (15 mL), and the mixture was stirred at 80°C for 3 hours. The iron powder was removed by filtration. Ethanol was evaporated, and the organic layer was extracted with ethyl acetate (2 × 50 mL) and H2O (100 mL), dried over Na2SO4, filtered, concentrated, and purified by column chromatography to give 3-3 (3.50 g, 10.2 mmol, 76.1% yield). LCMS: 342.0 [M+H] + ; Step 3: Preparation of 3-4

[0173] A mixture of 3-3 (3.00 g, 8.76 mmol) in HCl (12 M, 14.6 mL) and H2O (15 mL) was cooled to 0°C, and NaNO2 (1.81 g, 26.2 mmol) was added. The mixture was stirred for 30 min, and a mixture of NaI (9.20 g, 61.3 mmol) and CuI (834 mg, 4.38 mmol) in H2O (5 mL) was added dropwise. The mixture was stirred at 25°C for 2 h. The mixture was quenched with Na2S2O3 (aqueous solution, 30 mL), neutralized with Na2CO3 (aqueous solution, 30 mL), extracted with ethyl acetate (30 mL × 2), dried over Na2SO4, filtered, concentrated, and purified by HPLC to give 3-4 (700 mg, 2.16 mmol, 24.5% yield). LCMS: 322.9 [M+H] + ; Step 4: Preparation of 3-5

[0174] NaH (173 mg, 4.34 mmol, 60% purity) was added dropwise to a solution of 3-4 (700 mg, 2.17 mmol) in THF (10 mL) at 0°C, and the mixture was stirred at 25°C for 0.5 h. SEM-Cl (542 mg, 3.25 mmol, 575 μL) was added dropwise, and the mixture was stirred at 25°C for 1 h. NH4Cl (aqueous solution, 30 mL) was added to the mixture, and the mixture was extracted with ethyl acetate (2 × 30 mL). The organic layer was dried over Na2SO4, filtered, concentrated, and purified by column chromatography to give 3-5 (600 mg, 1.32 mmol, 61.0% yield) as a white solid. LCMS: 455.0 [M+3] + ; Step 5: Preparation of steps 3-6

[0175] A mixture of 3-5 (600 mg, 1.32 mmol), (4-(trifluoromethyl)phenyl)boronic acid (226 mg, 1.19 mmol), Pd(dppf)Cl2 (96.8 mg, 132 μmol), and K2CO3 (365 mg, 2.65 mmol) in dioxane (10 mL) and H2O (3 mL) was stirred at 80°C for 3 hours under a nitrogen atmosphere. The reaction mixture was extracted with ethyl acetate (2 × 10 mL) and H2O (10 mL), dried over Na2SO4, concentrated, and purified by column chromatography to give 3-6 (500 mg, 1.06 mmol, 72.10% yield). LCMS: 473.0 [M+3] + ; Step 6: Preparation of 3-7

[0176] A mixture of 3-6 (500 mg, 1.06 mmol), 2-(2,5-dihydrofuran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane (249 mg, 1.27 mmol), Pd(dppf)Cl2 (77.6 mg, 106 μmol), and K2CO3 (439 mg, 3.18 mmol) in dioxane (8 mL) and H2O (2 mL) was stirred at 85°C for 3 hours under a nitrogen atmosphere. The reaction mixture was extracted with ethyl acetate (2 × 10 mL) and H2O (10 mL), dried over Na2SO4, concentrated, and purified by column chromatography to give 3-7 (550 mg, 1.19 mmol, 93.8% yield). LCMS: 461.2 [M+H] + ; Step 7: Preparation of 3-8

[0177] Add 3-7 (500 mg, 1.09 mmol) to a suspension of Pd / C (100 mg, 10% purity) in MeOH (5 mL), and stir the mixture at 25°C for 2 hours under a H2 atmosphere. Filter the mixture and concentrate to give 3-8 (420 mg, crude product). LCMS: 463.3 [M+H] + ; Step 8: Preparation of Compound 3

[0178] The mixture of compound 3-8 (420 mg, 0.9 mmol) in TFA (1 mL) and DCM (2 mL) was stirred at 25°C for 3 hours. The mixture was concentrated and purified by HPLC to give compound 3 (13.0 mg, 39.1 μmol, 45.2% yield). LCMS: 333.3 [M+H] + . 1 HNMR (400 MHz, chloroform- d ) δ 1.90 - 11.03 (m, 1H), 8.16 (s, 1H), 7.83 (d, J = 1.4 Hz, 1H), 7.77 - 7.64 (m, 4H), 7.39 (d, J = 1.3 Hz, 1H), 4.40 (dt, J = 3.3, 8.8 Hz, 1H), 4.33 (d, J = 9.6 Hz, 1H), 4.01 (dd, J = 6.9,9.6 Hz, 1H), 3.89 - 3.72 (m, 2H), 2.71 - 2.52 (m, 1H), 2.04 (dtd, J = 4.4, 8.8, 13.1 Hz, 1H); Step 9: Preparation of compounds 1 and 2

[0179] NaH (72.2 mg, 1.81 mmol, 60.0% purity) was added to a solution of compound 3 (300 mg, 902 μmol) in THF (5 mL) at 0°C, and the mixture was stirred at 25°C for 0.5 h. MeI (192 mg, 1.35 mmol, 84.3 μL) was added dropwise at 0°C, and the mixture was stirred at 25°C for 1 h. An aqueous solution of NH4Cl (5 mL) was added to the mixture, and the mixture was extracted with ethyl acetate (2 × 5 mL), dried over Na2SO4, filtered, concentrated, and purified by preparative HPLC to give compound 1 (5.0 mg, 13.0 μmol, 1.44% yield) and compound 2 (15.0 mg, 43.0 μmol, 4.77% yield).

[0180] Compounds 8 to 20 were synthesized according to a similar procedure to that of compounds 1 to 3 or similar compounds of WO 2024067773. Table 3 Example A: Cell growth assay Cell culture

[0181] RPMI 1640 medium (Gibco, 31800) + 10% FBS (Biosera, FB-1058 / 500) for NCI-H226 cells (from ATCC). reagents

[0182] CellTiter-Glo reagent (CTG reagent, Promega, G7573). program

[0183] Cells were seeded into 384-well microplates (150 cells / well, 50 mL culture medium / well). An additional plate was also seeded as a day 0 control. The microplates were incubated overnight at 37°C with 5% CO2.

[0184] The compound was serially diluted 3-fold in DMSO, with the final maximum concentration being 30 mM, at 10 spots. 0.3% DMSO was used as a medium control. In addition, 25 mL / well of CTG reagent was added to additional plates and incubated at room temperature for 30 minutes, and the luminescence signal was detected using an EnVision (PerkinElmer, 2104 Multilabel Reader) as a day 0 control.

[0185] The plates treated with other compounds were incubated at 37°C for another 7 days, and 25 mL / well of CTG reagent was added to the plates. The plates were then incubated at room temperature for 30 minutes, and the luminescence signal was detected. Data Analysis

[0186] The day 0 luminescence signal was used as a negative control or baseline. Signal 第0天 = Average luminescence signal of control cells on day 0. Signal 空白对照 = Average emission signal of the blank control. Signal DMSO媒介物对照 = Average luminescence signal of DMSO-mediated control cells on day 7. Signal 化合物处理 = Day 7: Compound treatment of cell luminescence signals. Suppression % = 1 - (signal) 化合物处理 - Signal 空白对照 ) / (Signal DMSO媒介物对照 - Signal 空白对照 ) 100.

[0187] (Inhibitory concentration 50%, IC50) 50 The percentage of maximum inhibition (%) and maximum inhibition (%) were calculated using the dose-response curve. Example B: Thermal displacement measurement Experimental protocol

[0188] 1) Prepare fresh dilutions of Protein Thermal Shift™ dye (Applied Biosystems, 1000×) to 8×.

[0189] 2) To ensure the same DMSO concentration, the compound was diluted as follows: a 10 mM stock solution of the compound was prepared;

[0190] The final DMSO concentration was 0.1%.

[0191] 10 µM: Dilute the stock solution to 100 µM using PBS.

[0192] 1 µM: Dilute the stock solution to 1 mM using DMSO, and then to 10 µM using PBS.

[0193] 3) Preparation of TEAD protein:

[0194] TEAD1: The stock concentration is 2.9 mg / ml; the final concentration is 0.2 mg / ml.

[0195] 4) Place an appropriate reaction plate or tube on ice, and then prepare the protein melting reaction: Table 4

[0196] 5) Blow up and down on each reaction solution 10 times to mix them thoroughly.

[0197] 6) Seal the plate with MicroAmp™ optical adhesive film and centrifuge at 1000 rpm for 1 minute.

[0198] 7) Set up and run the qPCR instrument. Data Analysis

[0199] Analysis was performed using thermal Shift™ software v1.3. The data is shown in Table 5. Table 5 H226 CTG IC 50 :0 < A ≤ 100 nM; 100 nM < B ≤ 500 nM; 500 nM < C ≤ 1000nM; 1000 nM < D ≤ 30000 nM NT: Not tested

[0200] It should be understood that the examples and embodiments described herein are for illustrative purposes only, and various modifications or changes will be suggested to those skilled in the art based thereon, and will be included within the spirit and scope of this application and the appended claims. All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety for all purposes.

Claims

1. A compound of formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof: Formula (I), in: X is -N- or -CR X -; R X It is hydrogen, halogen, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 ynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, ynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Y is -N-, -CR Y -or-C(=O)-; R Y It is hydrogen, halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 ynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, ynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Ring A is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; Each R 1 Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl); wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally separated by one or more R 1a replace; Or two R atoms on the same atom 1 Together they form oxygen; Each R 1a Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 1a Together they form oxygen; n is 0, 1, 2, 3 or 4; Each L 1 and L 2 It does not exist independently, or it is -O-, -S-, or -NR. 2 -、-C(R 3 )2-、-C(R 3 )2-C(R 3 )2-、-C(R 3 )=C(R 3 )-、 -C(R) 3 )2O-、-OC(R 3 )2-、-C(R 3 )2S-、-SC(R 3 )2-、-C(R 3 )2NR 2 -or-NR 2 C(R 3 )2-; R 2 It is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 ynyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, alkenyl, ynyl, cycloalkyl and heterocycloalkyl is independently and optionally substituted by one or more R; Each R 3 Independently, it is hydrogen, halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 ynyl, cycloalkyl or heterocycloalkyl; wherein each alkyl, alkenyl, ynyl, cycloalkyl and heterocycloalkyl is independently and optionally substituted by one or more R; Or two Rs on the same carbon 3 Together they form oxygen; Or two Rs on the same carbon 3 Together they form a cycloalkyl or heterocycloalkyl group; each of the cycloalkyl or heterocycloalkyl group is optionally substituted with one or more R groups; Or two R on different carbons 3 Together they form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; each of the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group may optionally be substituted by one or more R groups; The ring C is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; Each R 7 It is independently hydrogen, halogen, -OH, or C1-C6 alkyl; p is 0, 1, 2, 3, 4, 5 or 6; R 8 is hydrogen, -C(=O)OR 9 , -C(=O)NR 10 R 11 , -C(=O)R 9 , -S(=O)₂NR 10 R 11 , , -S(=O)₂R 9 , -S(=O)R 9 , -P(=O)(OR 10 )(OR 11 ) or -B(OR 10 )(OR 11 ); R 9 It is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally influenced by one or more R 9a replace; Each R 9a Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 9a Together they form oxygen; R 10 and R 11 Each of the following is independently hydrogen, -CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl), or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently and optionally influenced by one or more R 10a replace; Or R 10 and R 11 Together with the atoms they are attached to, they form a group optionally bounded by one or more R atoms. 10b Substituted heterocyclic alkyl groups; Each R 10a Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 10a Together they form oxygen; Each R 10b Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 10b Together they form oxygen; U is either -C- or -N-; T is either -C- or -N-; The conditions are that U and T are not both -N-; and that U and T are both -C- when ring B is phenyl or a 6-membered heteroaryl. Ring B is absent, or is phenyl, 5- or 6-membered heteroaryl, 5- or 6-membered heterocycloalkyl, or C5-C7 cycloalkyl; Each R 12 Independently, it is halogen, -CN, -NO2, -OH, -OR a -OC(=O)R a -OC(=O)OR b -OC(=O)NR c R d -SF5, -SH, -SR a -S(=O)R a -S(=O)2R a -S(=O)2NR c R d -S(=O)(=NR) b )R b -NR c R d -NR b C(=O)NR c R d -NR b C(=O)R a -NR b C(=O)OR b -NR b S(=O)2R a -N=S(=O)(R b )2、-C(=O)R a -C(=O)OR b -C(=O)NR c R d -P(=O)(R b 2. C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or two R atoms on the same atom 12 Together they form oxygen; Or two Rs on the same carbon 12 Together they form a cycloalkyl or heterocycloalkyl group; each of the cycloalkyl or heterocycloalkyl group is optionally substituted with one or more R groups; Or two R on different atoms 12 Together they form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; each of the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group may optionally be substituted by one or more R groups; m is 0, 1, 2, 3, 4, 5, or 6; Or an R 12 and R Y Together they form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group; each of the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group may optionally be substituted by one or more R groups; Each R a Independently, it is a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl) or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Each R b Independently, it is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl) or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; R c and R d Each of the following is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, C1-C6 heteroalkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkylene (cycloalkyl), C1-C6 alkylene (heterocycloalkyl), C1-C6 alkylene (aryl) or C1-C6 alkylene (heteroaryl), wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is independently and optionally substituted by one or more R; Or R c and R d Together with the atoms to which they are attached, they form heterocyclic alkyl groups optionally substituted with one or more R atoms; and Each R is independently a halogen, -CN, -OH, -SF5, -SH, -S(=O)C1-C3 alkyl, -S(=O)2C1-C3 alkyl, -S(=O)2NH2, -S(=O)2NHC1-C3 alkyl, -S(=O)2N(C1-C3 alkyl)2, -S(=O)(=NC1-C3 alkyl)(C1-C3 alkyl), -NH2, -NHC1-C3 alkyl, -N(C1-C3 alkyl)2, -N=S(=O)(C1-C3 alkyl) 2. -C(=O)C1-C3 alkyl, -C(=O)OH, -C(=O)OC1-C3 alkyl, -C(=O)NH2, -C(=O)NHC1-C3 alkyl, -C(=O)N(C1-C3 alkyl)2, -P(=O)(C1-C3 alkyl)2, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl, C1-C3 heteroalkyl or C3-C6 cycloalkyl; Or two R atoms on the same atom form an oxo group; The condition is that if ring C is cyclopropyl, then ring B does not exist.

2. The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the compound is a compound of formula (Ia) or (Ib): Formula (Ia), Equation (Ib), Wherein the ring C is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, provided that the ring C is not a cyclopropyl group.

3. The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the compound is a compound of formula (Ic): Formula (Ic), The ring C is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group.

4. The compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein the compound is a compound of formula (1d): Formula (Id), Wherein the ring C is a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, provided that the ring C is not a cyclopropyl group.

5. The compound according to any one of claims 1-3, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each L 1 and L 2 It does not exist independently, or it is -O- or -C(R). 3 )2 or -NR 2 - 6. The compound of any one of claims 1-3 or 5, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 3 It is independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl.

7. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein ring A is phenyl.

8. The compound of any one of claims 1-7, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 1 Independently, it is halogen, -CN, -OH, -OR a -NR c R d C1-C6 alkyl or C1-C6 haloalkyl.

9. The compound of any one of claims 1-8, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein n is 0, 1 or 2.

10. The compound of any one of claims 1-9, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 8 It is -C(=O)OR 9 -C(=O)NR 10 R 11 or -S(=O)2NR 10 R 11 .

11. The compound of any one of claims 1-10, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 9 It is hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl.

12. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 10 and R 11 Each is independently hydrogen or C1-C6 alkyl.

13. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 10 and R 11 Each is independently hydrogen or optionally composed of one or more R 10a Substituted heterocyclic alkyl groups.

14. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 10 and R 11 Together with the atoms they are attached to, they form a group optionally bounded by one or more R atoms. 10b Substituted heterocyclic alkyl groups.

15. The compound of any one of claims 1-14, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 10b Independently -OH, -OR a or -NR c R d .

16. The compound of any one of claims 1-2 or 4-15, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein ring B is phenyl.

17. The compound of any one of claims 1-2 or 4-15, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein ring B is a 5- or 6-membered heteroaryl group.

18. The compound of any one of claims 1-2 or 4-15, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein ring B is a 5-membered heteroaryl group.

19. The compound of any one of claims 1-2 or 4-15, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein ring B is pyrroleyl, furanyl, thiophenyl, imidazoyl, pyrazolyl, thiazoyl, oxazolyl, or triazolyl.

20. The compound of any one of claims 1-19, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 12 It is independently a halogen, -CN, -OH, C1-C6 alkyl, C1-C6 haloalkyl, cycloalkyl or heterocycloalkyl.

21. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein m is 0 or 1.

22. A compound, or a pharmaceutically acceptable salt or stereoisomer thereof, selected from the compounds in Table 1 or Table 2.

23. A pharmaceutical composition comprising a compound as described in any one of claims 1-22, or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.

24. A method of treating a subject with cancer or fibrosis, the method comprising administering to the subject an effective amount of the compound as described in any one of claims 1-23, or a pharmaceutically acceptable salt or stereoisomer thereof.

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