Inhibitor and degradation agent of PIP4K protein

Abstract

Compounds and compositions of Formula (I ') are provided that modulate the level or activity of PIP4K2A, PIP4K2B, or PIP4K2C. Also provided are methods of treating a disease or condition by modulating (e.g., reducing) the level or activity of PIP4K2A, PIP4K2B, or PIP4K2C, comprising administering such compounds and compositions.

Description

Cross-reference to related applications

[0001] This application claims priority to U.S. Provisional Application No. 63 / 465,458, filed May 10, 2023; U.S. Provisional Application No. 63 / 611,367, filed December 18, 2023; and U.S. Provisional Application No. 63 / 575,561, filed April 5, 2024, the contents of which are hereby incorporated in their entirety by reference for all purposes. Background Technology

[0002] Phosphatidylinositol 5-phosphate 4-kinase (PI5P4K), composed of three isoforms PI5P4Kα, β, and γ, is a lipid kinase that catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PI5P) at its 4-position to form phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2) (Rameh et al., Nature). 390(6656) :192-196 (1997). In the cell membrane, PI-4,5-P2 is also produced via another signaling pathway, in which phosphatidylinositol 4-phosphate (PI4P) is phosphorylated by phosphatidylinositol 4-phosphate 5-kinase (PI4P5K).

[0003] Although most PI-4,5-P2 is produced via the PI4P5K pathway, PI5P4K has been identified as a key regulator of many cellular functions, including metabolism, stress response, autophagy, and immune processes (Hu et al., J. Lipid Res.). 59 :507-514 (2018); Lamia et al., Mol. Cell. Biol. 24(11) :5080-5087 (2004); Shim et al., Proc. Natl. Acad. Sci. USA 113(27) :7596-7601 (2016); Al-Ramahi et al., eLife 6 :e29123 (2017); Lundquist et al., Mol. Cell 70(3) :531-543 (2018); Bulley et al., Proc. Natl. Acad. Sci. USA 113(38) :10571-10576 (2016); Keune et al., Adv. Biol. Regul. 53(2) :179-189 (2013)). PIP4K has different catalytic and non-catalytic functions in controlling cellular metabolism and inhibiting PIP5K activity and insulin-stimulated PI(3,4,5)P3 production (Wang et al., Cell Rep.).27 :1991-2001(2019)).

[0004] Dysregulation of the PI5P4K signaling pathway is further associated with diseases such as diabetes, neurodegenerative diseases, and cancer (Lamia et al., Mol. Cell. Biol.). 24(11) : 5080-5087 (2004); Al-Ramahi et al., eLife 6:e29123 (2017); Jude et al., Oncogene 34(10) :1253-1262 (2015); Luoh et al., Oncogene 23 :1354-1363 (2004); Emerling et al., Cell 155(4) :844-857 (2013). Analysis of PI(4,5)P2 levels in cells with single or double PIP4K isoform knockdown revealed an additive effect among all three isoforms, independent of their relative catalytic activity. Double knockdown of the most active isoform, PIP4KA / B, failed to produce a triple knockdown, suggesting that catalytic activity is not the most important factor regulating PI(4,5)P2 levels (Wang et al., Cell Rep.27:1991-2001 (2019), and indicating a unique role for PIP4KC.

[0005] These findings suggest that inhibition of PI5P4K kinase activity and / or degradation of PI4P4K may have therapeutic potential in a variety of diseases. Summary of the Invention

[0006] In one respect, a compound of formula (I') is provided: (I'), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein Q, V, R, ring 1, ring 3 and ring 4 are as detailed herein.

[0007] In one aspect, a compound of formula (I) is provided: (I), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein Q, V, R, ring 1, ring 3, and ring 4 are as detailed herein. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, or any variations or embodiments thereof.

[0008] In some embodiments of the compound of formula (I), Q is ring 5, as detailed herein. In some embodiments, a compound of formula (II) is provided: (II), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein V, R, ring 1, ring 3, ring 4, and ring 5 are as detailed herein. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, or any variations or embodiments thereof.

[0009] In some embodiments of the compound of formula (I), Q is R Q As detailed herein. In some embodiments, a compound of formula (III) is provided: (III), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein V, R, ring 1, ring 3, ring 4 and R Q As detailed herein. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, or any variations or embodiments thereof.

[0010] In some embodiments of the compound of formula (I), Q has the characteristics of formula (i). (i), Rings A, X, B, W, C, the connector, U, and 2 are described in detail herein. In some embodiments, a compound of formula (IV) is provided: (IV), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein rings A, X, B, W, C, linker, U, 2, V, 1, 3, and 4 are as detailed herein. In some variations, the embodiments provided herein also apply to compounds of formula (I'), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, or any variations or embodiments thereof.

[0011] In another aspect, a pharmaceutical composition is provided, the pharmaceutical composition comprising formula (I), (II), (III) or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy) (IV-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers. In some embodiments, a pharmaceutical composition is provided comprising a therapeutically effective amount of formula (I), (II), (III), or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix). Compounds of (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In another aspect, a pharmaceutical composition is provided, the pharmaceutical composition comprising formula (I'), or any related formula such as formula (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-a c), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers. In some embodiments, a pharmaceutical composition is provided comprising a therapeutically effective amount of formula (I'), or any related formula such as (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab). Compounds of (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.

[0012] On the other hand, a method is provided for manufacturing compounds of formula (I), (II), (III), (III) or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or tautomers or stereoisomers thereof, or pharmaceutically acceptable salts of any of the foregoing. On the other hand, a manufacturing formula (I') or any related formula such as formula (I), (II), (III), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I- The method of using a compound of (ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

[0013] On the other hand, a method for treating a disease or condition is provided, the method comprising regulating (e.g., reducing) the activity or level of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, comprising administering (a) of formula (I), (II), (III), or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (I... Compounds of p), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their interrelationships. A variant or stereoisomer, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising formula (I), (II), (III) or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), ( Compounds of (Ix), (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers. In some embodiments, the method includes reducing the activity of PIP4K2C. In some embodiments, the method includes selectively reducing the activity of PIP4K2C. In some embodiments, the method includes selectively reducing the level of PIP4K2C. In some embodiments, the method includes selectively degrading PIP4K2C.On the other hand, a method for treating a disease or condition is provided, the method comprising regulating (e.g., reducing) the activity or level of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, including administering formula (a) (I'), or any related formula such as formulas (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz). Compounds of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or any of the foregoing. (a) a pharmaceutically acceptable salt, or (b) a pharmaceutical composition comprising formula (I'), or any related formula such as (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac The method comprises compounds of the order (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers. In some embodiments, the method includes reducing the activity of PIP4K2C. In some embodiments, the method includes selectively reducing the activity of PIP4K2C. In some embodiments, the method includes selectively reducing the level of PIP4K2C.In some implementations, the method includes selectively degrading PIP4K2C.

[0014] On the other hand, a method for treating a disease or condition is provided, the method comprising modulating (e.g., reducing) the activity or level of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, comprising administering (a) a therapeutically effective amount of formula (I), (II), (III), or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io). Compounds of (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their interrelationships. (a) a variant or stereoisomer, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a therapeutically effective amount of formula (I), (II), (III) or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw) The method comprises compounds of (Ix), (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers. In some embodiments, the method includes reducing the activity of PIP4K2C. In some embodiments, the method includes selectively reducing the activity of PIP4K2C. In some embodiments, the method includes selectively reducing the level of PIP4K2C. In some embodiments, the method includes selectively degrading PIP4K2C. In some embodiments, the method is more selective for PIP4K2C than for PIP4K2A. In some implementations, the method is more selective for PIP4K2C than for PIP4K2B.In some embodiments, the method is more selective for PIP4K2C than for both PIP4K2A and PIP4K2B. In another aspect, a method for treating a disease or condition is provided, the method comprising modulating (e.g., reducing) the activity or level of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, comprising administering (a) a therapeutically effective amount of formula (I'), or any related formula such as formulas (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), ( Compounds of (I-z), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their tautomers or stereoisomers, or any of the foregoing. (a) a pharmaceutically acceptable salt, or (b) a pharmaceutical composition comprising a therapeutically effective amount of formula (I'), or any related formula such as (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I... Compounds of the order (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers. In some embodiments, the method includes reducing the activity of PIP4K2C.In some embodiments, the method includes selectively reducing the activity of PIP4K2C. In some embodiments, the method includes selectively reducing the level of PIP4K2C. In some embodiments, the method includes selectively degrading PIP4K2C. In some embodiments, the method is more selective for PIP4K2C than for PIP4K2A. In some embodiments, the method is more selective for PIP4K2C than for PIP4K2B. In some embodiments, the method is more selective for PIP4K2C than for both PIP4K2A and PIP4K2B.

[0015] On the other hand, a method for treating a disease or condition is provided, the method comprising regulating (e.g., reducing) the level of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, comprising administering to a subject in need a compound of formula (a), (IV), or any related formula such as (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or The method comprises (b) a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or (c) a pharmaceutical composition comprising a compound of formula (IV), or any related formula such as (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable carrier. In some embodiments, the method includes reducing the level of PIP4K2C. In some embodiments, the method includes selectively reducing the level of PIP4K2C. In some embodiments, the method includes degrading PIP4K2C. In some embodiments, the method includes selectively degrading PIP4K2C.

[0016] On the other hand, a method for treating a disease or condition is provided, the method comprising regulating (e.g., reducing) the level of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, comprising administering to a subject in need (a) a therapeutically effective amount of a compound of formula (IV), or any related formula such as (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or The method comprises (a) a tautomer or stereoisomer of PIP4K2C, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (IV), or any related formula such as (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or a tautomer or stereoisomer of PIP4K2C, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable carrier. In some embodiments, the method includes reducing the level of PIP4K2C. In some embodiments, the method includes degrading PIP4K2C. In some embodiments, the method includes selectively reducing the level of PIP4K2C. In some embodiments, the method includes selectively degrading PIP4K2C.

[0017] On the other hand, a method is provided to enhance the immune function of a subject in need, the method comprising administering to the subject formula (a) of formula (I), (II), (III), or (IV), or any related formula such as formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu). Compounds of (Iv), (Iw), (Ix), (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or any of the foregoing. (a) a pharmaceutically acceptable salt, or (b) a pharmaceutical composition comprising formula (I), (II), (III) or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy). Compounds of (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.On the other hand, a method is provided to enhance the immune function of a subject in need, the method comprising administering to the subject formula (a) (I'), or any related formula such as formula (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz) Compounds of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or any of the foregoing. (a) a pharmaceutically acceptable salt, or (b) a pharmaceutical composition comprising formula (I'), or any related formula such as (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.

[0018] In some embodiments, a method for enhancing the immune function of a subject in need is provided, the method comprising administering to the subject (a) a therapeutically effective amount of formula (I), (II), (III), or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It) Compounds of (Iu), (Iv), (Iw), (Ix), (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or any of the preceding compounds. (a) a pharmaceutically acceptable salt of one of the ingredients, or (b) a pharmaceutical composition comprising a therapeutically effective amount of formula (I), (II), (III) or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), ( Compounds of (II-y), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some implementations, a method for enhancing the immune function of a subject in need is provided, the method comprising administering to the subject (a) a therapeutically effective amount of formula (I'), or any related formula such as formula (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy) Compounds of (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or any of the preceding compounds. (a) a pharmaceutically acceptable salt of one, or (b) a pharmaceutical composition comprising a therapeutically effective amount of formula (I'), or any related formula such as (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), ( Compounds of (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.

[0019] In some aspects, the present invention relates to a method for stimulating the immune system, said method comprising reducing, in a subject in need, the scaffolding or interaction of at least one of PIP4K2A, PIP4K2B, and PIP4K2C with at least one of PIP4K2A, PIP4K2B, or phosphatidylinositol-4-phosphate 5-kinase (PIP5K), including administering to the subject (a) of formula (I), (II), (III), or (IV), or any related formula such as formula (Ia), (Ib), (Ic), (Id), (Ie), (If), or (Ig). , (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (II-a), (II-b ), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j (a) A compound of formula (I), (II), (III), (III), or (IV), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or (b) a pharmaceutical composition comprising formula (I), (II), (III), (III), or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Ib), (Ic), (Id), (Ir), (Is), (Id), (Iq), (Ir), (Is), (Id), (Iq), (Ir), (Is), (Id), (Iq), (Ic ... Compounds of (Iu), (Iv), (Iw), (Ix), (Iy), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers. In some embodiments, the method includes reducing the scaffolding or interaction of PIP4K2C with at least one of PIP4K2A, PIP4K2B, or phosphatidylinositol-4-phosphate 5-kinase (PIP5K).In some aspects, the present invention relates to a method for stimulating the immune system, said method comprising reducing, in a subject in need, the scaffolding or interaction of at least one of PIP4K2A, PIP4K2B, and PIP4K2C with at least one of PIP4K2A, PIP4K2B, or phosphatidylinositol-4-phosphate 5-kinase (PIP5K), including administering to the subject formula (a) (I'), or any related formula such as formula (I), (II), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im). , (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-a g), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j (a) compounds of (IV-k) or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, or (b) pharmaceutical compositions comprising formula (I'), or any related formula such as (I), (II), (III), (III), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (I... Compounds of (I-z), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, the method includes reducing the scaffolding or interaction of PIP4K2C with at least one of PIP4K2A, PIP4K2B, or phosphatidylinositol-4-phosphate 5-kinase (PIP5K).

[0020] Any embodiment of a compound of formula (I) or (I') provided herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation thereof, or embodiment thereof, shall, where applicable, be applicable to any other formula detailed herein, as if each embodiment were specifically and individually listed. Therefore, it should be understood and described that each embodiment of a compound of formula (I) or (I') provided herein, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or any variation thereof, or embodiment thereof, such as with ring 1, ring 2, ring 3, ring 4, ring 5, ring A, ring B, ring C, R, R 1 R 2a R 2b R 3a R 3b R 4a R 4b R 5a R 5b R C R D R L R Q R V R w R x R y R z Q, U, V, X, W, connector, L 1 L 2 L 3The implementation schemes related to n are applicable to equations (i), (ii), (iii), (iv), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac). Any of (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), as each embodiment is specifically and individually listed. It should also be understood and described that all such embodiments can be used in any of pharmaceutical compositions, methods, kits, uses, etc., that include such compounds or other aspects detailed herein.

[0021] As shown in the working examples, the compounds covered by formulas (I') and (I) inhibit the activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C or promote their degradation. In some embodiments, the compounds covered by formulas (I') and (I) inhibit the activity of PIP4K2C or promote its degradation.

[0022] Not intended to be bound by any particular theory, compounds of formula (IV) and any applicable related formulas, such as (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l) are believed to recruit the cell's ubiquitin / proteasome system to close proximity to PIP4K2A, PIP4K2B, or PIP4K2C due to binding between PIP4K2A, PIP4K2B, or PIP4K2C and a target ligand, causing degradation of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, which functions to routinely identify and remove damaged proteins. Following the destruction of PIP4K2A, PIP4K2B, or PIP4K2C proteins, the degrading agent is released and remains active. Therefore, by engaging with and utilizing the body's own natural protein disposal system, the compounds of this invention represent a potential improvement over current small molecule inhibitors of PIP4K2A, PIP4K2B, and PIP4K2C, and overcome one or more limitations regarding their use. Consequently, the effective intracellular concentration of the degrader can be significantly lower than that of small molecule PIP4K2A, PIP4K2B, or PIP4K2C inhibitors. Furthermore, while knockdown or deletion of the PIP4K2A, PIP4K2B, and / or PIP4K2C genes can be used to reduce the cellular concentration or amount of these proteins, post-translational disruption and degradation of PIP4K2A, PIP4K2B, and / or PIP4K2C proteins are preferred. Directly targeting the protein, rather than via the DNA or mRNA molecules encoding the protein, is a more direct and rapid method for reducing the scaffolding function of PIP4K proteins. Therefore, degradation can allow some catalytic functions of PIP4K2A, PIP4K2B, and / or PIP4K2C to proceed, while reducing non-catalytic functions, such as scaffolding between PIP4K2A, PIP4K2B, and / or PIP4K2C proteins and other cellular proteins and structures. In summary, the compounds of this invention represent a new set of chemical tools for knocking down at least one of PIP4K2A, PIP4K2B, and PIP4K2C, and may provide potential therapeutic modalities for PIP4K2A, PIP4K2B, and / or PIP4K2C-related cancers and autophagy-dependent diseases (e.g., neurodegenerative diseases, insulin). In some cases, the compounds of this invention represent a new set of chemical tools for PIP4K2C knockdown and may provide potential therapeutic modalities for PIP4K2C-related cancers and autophagy-dependent diseases (e.g., neurodegenerative diseases, insulin). These compounds can be used to enhance immune function, as in, for example, US20220168402A1 and Wang et al., Cell Rep. 27The descriptions in WO 2022 / 246025 are all incorporated herein by reference. Inhibitors and degraders of the PIP4K protein, as well as methods for treating diseases or disorders by modulating the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, are also disclosed in WO 2022 / 246025, which is incorporated herein by reference in its entirety. Attached Figure Description

[0023] Figure 1 This study demonstrates the regulation of phagocytosis by compound U. The degradation of PIP4K2C by compound U in human dendritic cells enhances their phagocytosis of E. coli bioparticles, highlighting the inherent immunological benefits of PIP4K2C targeting in bone marrow-like cells.

[0024] Figure 2A Compound U demonstrated its ability to reduce tumor growth in the mouse syngeneic colorectal cancer model MC38-OVA. A significant reduction in tumor growth was observed in the treatment group compared to the vector control group. Figure 2B The study showed the survival of mice treated with compound U and mice treated with a control drug.

[0025] Figure 3 Compound U was shown to enhance the phagocytosis of *E. coli* bioparticles in human dendritic cells by degrading PIP4K2C. No enhanced phagocytosis was observed when using PIP4K2C inhibitory compounds that do not induce degradation, demonstrating the unique effect of PIP4K2C degraders relative to individual inhibitory compounds.

[0026] Figure 4 The study showed that the degradation of PIP4K2C by compound U in dendritic cells led to increased uptake of dying tumor-derived materials, thereby increasing the phagocytosis of PIP4K2C-deficient tumor cells by immune cells.

[0027] Figure 5A Compound U was shown to degrade endogenous PIP4K2C in rats in vivo. Figure 5B Compound U was shown to degrade endogenous PIP4K2C in vivo in dogs. Detailed Implementation

[0028] definition For the purposes of this document, unless otherwise expressly stated, the terms “an”, “a”, etc., refer to one (species) or more (species).

[0029] This document refers to “about” a value or parameter that includes (and describes) an implementation of the value or parameter itself. For example, “about X” includes and describes “X” itself.

[0030] Unless otherwise stated, as used herein, "alkyl" means and includes alkyl groups having a specified number of carbon atoms (i.e., C46, ​​C56, C6 ... 1-10 This refers to a straight-chain (i.e., unbranched) or branched monovalent hydrocarbon chain, or a combination thereof, having one to ten carbon atoms. Specific alkyl groups are those having 1 to 10 carbon atoms (“C1-C1”). 10 Alkyl groups, having 6 to 10 carbon atoms ("C6-C") 10 Alkyl groups are those groups having 1 to 6 carbon atoms (“C1-C6 alkyl”), 2 to 6 carbon atoms (“C2-C6 alkyl”), or 1 to 4 carbon atoms (“C1-C4 alkyl”). Specific C1-C4 alkyl groups include C1-C3 alkyl groups. Examples of alkyl groups include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, etc.

[0031] As used herein, "alkylene" refers to residues that are identical to alkyl but have a divalent oxidation state. Specific alkylene groups are those having 1 to 10 carbon atoms ("C1-C1"). 10 Alkylenes ("C6-C10") have 6 to 10 carbon atoms. 10 Alkylenes are those having 1 to 6 carbon atoms ("C1-C6 alkylenes"), 1 to 5 carbon atoms ("C1-C5 alkylenes"), 1 to 4 carbon atoms ("C1-C4 alkylenes"), or 1 to 3 carbon atoms ("C1-C3 alkylenes"). Examples of alkylenes include, but are not limited to, groups such as methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), isopropylene (-CH2CH(CH3)-), butylene (-CH2(CH2)2CH2-), isobutylene (-CH2CH(CH3)CH2-), pentylene (-CH2(CH2)3CH2-), hexylene (-CH2(CH2)4CH2-), heptylene (-CH2(CH2)5CH2-), octylene (-CH2(CH2)6CH2-), etc.

[0032] Unless otherwise stated, as used herein, "carbocyclic group" means and includes groups having a specified number of carbon atoms (i.e., C3-C3). 10 Cycloalkyl refers to saturated and partially unsaturated hydrocarbon structures (meaning three to ten carbon atoms). Cycloalkyl can consist of one ring (e.g., cyclohexyl) or multiple rings (e.g., adamantyl). In polycyclic systems, one or more fused rings can be carbocyclic or aryl (e.g., spiro[4.5]decyl or 1,2,3,4-tetrahydronaphthyl), but not heterocyclic or heteroaryl. Carbocyclic groups containing more than one ring can be fused, spirocyclic, or bridged, or combinations thereof. Specific carbocyclic groups are those having 3 to 12 cyclic carbon atoms (“C…”). 3-12(Carbocyclic group), having 3 to 10 cyclic carbon atoms ("C") 3-10 A carbocyclic group (“C3-C8 carbocyclic”), having 3 to 6 cyclic carbon atoms (“C3-C6 carbocyclic”), or having 3 to 4 cyclic carbon atoms (“C3-C4 carbocyclic”). A carbocyclic group having more than one ring (at least one of which is aromatic) may be attached to the parent structure at an aromatic ring position or a non-aromatic ring position. In one variation, the carbocyclic group having more than one ring (at least one of which is aromatic) is attached to the parent structure at an aromatic ring position. In another variation, the carbocyclic group having more than one ring (at least one of which is aromatic) is attached to the parent structure at a non-aromatic ring position.

[0033] Unless otherwise stated, as used herein, "cycloalkyl" means and includes alkyl groups having a specified number of carbon atoms (i.e., C3-C4). 10 A saturated cyclic hydrocarbon structure (meaning three to ten carbon atoms). A cycloalkyl group may consist of one ring (e.g., cyclohexyl) or multiple rings (e.g., adamantyl). In polycyclic systems, one or more of the fused rings may be cycloalkyl or aryl (e.g., spiro[4.5]decyl or 1,2,3,4-tetrahydronaphthyl), but not heterocyclic or heteroaryl. A cycloalkyl group containing more than one ring may be fused, spirocyclic, or bridged, or a combination thereof. A specific cycloalkyl group is one having 3 to 12 cyclic carbon atoms (“C…”). 3-12 cycloalkyl groups), having 3 to 10 cyclic carbon atoms ("C") 3-10 Cycloalkyl groups are those groups having 3 to 8 cyclic carbon atoms (“C3-C8 cycloalkyl”), 3 to 6 cyclic carbon atoms (“C3-C6 cycloalkyl”), or 3 to 4 cyclic carbon atoms (“C3-C4 cycloalkyl”). Examples of cycloalkyl groups include (but are not limited to) cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornel, etc. Cycloalkyl groups having more than one ring (at least one of which is aromatic) may be attached to the parent structure at an aromatic ring position or a non-aromatic ring position. In one variation, a cycloalkyl group having more than one ring (at least one of which is aromatic) may be attached to the parent structure at an aromatic ring position. In another variation, a cycloalkyl group having more than one ring (at least one of which is aromatic) may be attached to the parent structure at a non-aromatic ring position.

[0034] As used herein, “aryl” or “Ar” refers to an unsaturated aromatic carbocyclic group having a single ring (e.g., phenyl) or multiple condensed rings (e.g., naphthyl or anthracene), wherein the condensed rings must be aromatic. Specific aryl groups are those having 6 to 14 cyclic carbon atoms (“C6-C6”). 14 Those groups (aryl group).

[0035] As used herein, "heteroaryl" refers to an unsaturated aromatic cyclic group having 1 to 14 cyclic carbon atoms and at least one cyclic heteroatom (including, but not limited to, heteroatoms of nitrogen, oxygen, and sulfur). A heteroaryl may have a single ring (e.g., pyridyl, furanyl) or multiple condensed rings (e.g., indazinyl, benzothiopheneyl), wherein the condensed ring must be aromatic. Specific heteroaryls are 5- to 14-membered rings having 1 to 12 cyclic carbon atoms and 1 to 6 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur; 5- to 10-membered rings having 1 to 8 cyclic carbon atoms and 1 to 4 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 5-, 6-, or 7-membered rings having 1 to 5 cyclic carbon atoms and 1 to 4 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur. In one variation, the specific heteroaryl group is a monocyclic aromatic 5-, 6-, or 7-membered ring having 1 to 6 cyclic carbon atoms and 1 to 4 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur. In another variation, the specific heteroaryl group is a polycyclic aromatic ring having 1 to 12 cyclic carbon atoms and 1 to 6 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur. The heteroaryl group may be attached to the parent structure at a cyclic carbon atom or a cyclic heteroatom.

[0036] As used herein, “heterocyclic,” “heterocyclic,” or “heterocyclic group” refers to a saturated or partially unsaturated nonaromatic cyclic group having a monocyclic or multiple condensed rings and 1 to 14 cyclic carbon atoms and 1 to 6 cyclic heteroatoms such as nitrogen, sulfur, or oxygen. Heterocyclic groups comprising more than one ring can be fused, bridged, or spirocyclic, or any combination thereof. In fused ring systems, one or more fused rings can be cycloalkyl, aryl, or heteroaryl. Heterocyclic groups may optionally be independently substituted by one or more substituents described herein. The specific heterocyclic group is a 3- to 14-membered ring having 1 to 13 cyclic carbon atoms and 1 to 6 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 12-membered ring having 1 to 11 cyclic carbon atoms and 1 to 6 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 10-membered ring having 1 to 9 cyclic carbon atoms and 1 to 4 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 3- to 8-membered ring having 1 to 7 cyclic carbon atoms and 1 to 4 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 3- to 6-membered ring having 1 to 5 cyclic carbon atoms and 1 to 4 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur. In one variation, the heterocyclic group comprises a monocyclic 3-, 4-, 5-, 6-, or 7-membered ring having 1 to 2, 1 to 3, 1 to 4, 1 to 5, or 1 to 6 cyclic carbon atoms and 1 to 2, 1 to 3, or 1 to 4 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur. In another variation, the heterocyclic group comprises a polycyclic non-aromatic ring having 1 to 12 cyclic carbon atoms and 1 to 6 cyclic heteroatoms independently selected from nitrogen, oxygen, and sulfur. A heterocyclic group having more than one ring (at least one of which is aromatic) may be attached to the parent structure at an aromatic ring position or a non-aromatic ring position. In one variation, a heterocyclic group having more than one ring (at least one of which is aromatic) may be attached to the parent structure at an aromatic ring position. In another variation, a heterocyclic group having more than one ring (at least one of which is aromatic) may be attached to the parent structure at a non-aromatic ring position.

[0037] "Halogen" or "halogen" refers to an element in Group 7 of the periodic table. Preferred halogens include fluorine, chlorine, bromine, and iodine. Where a residue is substituted by more than one halogen, it can be referred to by using a prefix corresponding to the number of halogen moieties attached, such as dihaloaryl, dihaloalkyl, trihaloaryl, etc., which refer to aryl and alkyl groups substituted by two ("di") or three ("tri") halogen groups, which may be, but are not necessarily, the same halogen; thus, 4-chloro-3-fluorophenyl falls within the range of dihaloaryl. An alkyl group in which each hydrogen atom is replaced by a halogen group is called a "perhaloalkyl". A preferred perhaloalkyl is trifluoromethyl (-CF3). Similarly, "perhaloalkoxy" refers to an alkoxy group in which a halogen replaces each H atom in the hydrocarbon constituting the alkyl moieties of the alkoxy group. An example of a perhaloalkoxy is trifluoromethoxy (-OCF3).

[0038] "Carbonyl" refers to the group C=O.

[0039] "Oxide group" refers to a part that equals O.

[0040] Unless otherwise stated, "optionally substituted" means that the group may be unsubstituted or substituted with one or more (e.g., 1, 2, 3, 4, or 5) of the substituents listed for the group, wherein the substituents may be the same or different. In one embodiment, the optionally substituted group has one substituent. In another embodiment, the optionally substituted group has two substituents. In another embodiment, the optionally substituted group has three substituents. In another embodiment, the optionally substituted group has four substituents. In some embodiments, the optionally substituted group has 1 to 2, 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, or 2 to 5 substituents. In one embodiment, the optionally substituted group is unsubstituted.

[0041] It should be understood that the aspects and implementation schemes described herein as "included" include "consisting of implementation schemes" and "substantially consisting of implementation schemes".

[0042] As used herein, the term "pharmaceutically acceptable salt" for a given compound refers to a salt that retains the biological efficacy and properties of the given compound and is biologically or otherwise desirable. "Pharmaceutically acceptable salt" includes, for example, salts formed with inorganic acids and salts formed with organic acids. Furthermore, if the compound described herein is obtained as an acid addition salt, the free base can be obtained by alkalizing a solution of the acidic salt. Conversely, if the product is a free base, the addition salt, particularly a pharmaceutically acceptable addition salt, can be produced according to the conventional procedure for preparing acid addition salts from basic compounds by dissolving the free base in a suitable organic solvent and treating the solution with acid. See, for example... Handbook of Pharmaceutical Salts Properties, Selection, and Use[Reference: International Union of Pure and Applied Chemistry, John Wiley & Sons (2008), which is incorporated herein by reference.] Those skilled in the art will recognize a variety of synthetic methods that can be used to prepare pharmaceutically acceptable addition salts that are non-toxic. Pharmaceutically acceptable acid addition salts can be prepared from inorganic or organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, gluconic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, trifluoroacetic acid, etc. Similarly, pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include (by example only) sodium, potassium, lithium, aluminum, ammonium, calcium, and magnesium salts. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines. Specific examples of suitable amines include (by example only) isopropylamine, trimethylamine, diethylamine, tri(isopropyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, etc.

[0043] Some of the compounds described herein may exist as tautomers. These tautomers are in equilibrium with each other. By way of illustration, amide-containing compounds may exist in equilibrium with their imine tautomers. Regardless of which tautomer is shown and regardless of the nature of the equilibrium between the tautomers, those skilled in the art will understand that the compounds disclosed herein comprise both amide and imine tautomers. Therefore, for example, amide-containing compounds should be understood to include their imine tautomers. Similarly, imine-containing compounds should be understood to include their amide tautomers.

[0044] The compounds disclosed herein, or pharmaceutically acceptable salts thereof, may include asymmetric centers and thus may produce enantiomers, diastereomers, and other stereoisomers, which can be defined according to the absolute stereochemical definition (…). R )-or( S (or for amino acids, (D)- or (L)-). This disclosure is intended to include all such possible isomers, as well as their racemic and optically pure forms and mixtures thereof in any ratio. Optically active (+) and (-), ( R )-and( S(D)- and (L)- isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques such as chromatography and / or fractional crystallization. Conventional techniques for preparing / separating individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of racemic mixtures (or racemic mixtures of salts or derivatives) using chiral high-performance liquid chromatography (HPLC) and chiral supercritical fluid chromatography (SFC), for example. Unless otherwise specified, this disclosure is intended to include both E and Z geometrical isomers when the compounds described herein contain an olefinic double bond or other geometrically asymmetric centers. Similarly, cis- and trans- are used in their conventional sense to describe relative spatial relationships.

[0045] "Stereoisomers" refer to compounds composed of identical atoms bonded by identical bonds but with different three-dimensional structures, which are not interchangeable. This disclosure contemplates various stereoisomers or mixtures thereof (e.g., racemic mixtures), and includes "enantiomers," which are two stereoisomers whose structures are mirror images of each other and not superimposed. "Diabeta-isomers" are stereoisomers having at least two asymmetric atoms, but not mirror images of each other. In cases where enantiomeric and / or diastereomeric forms exist for a given structure, flattened bonds indicate the existence of all stereoisomeric forms of the described structure, for example... In cases where an enantiomer and / or diastereomer exists in a given structure, unless otherwise indicated, the absence of wedge-shaped or cleaving bonds bearing the symbols “R,” “S,” or “abs” indicates that the composition consists of a mixture of at least 90% by weight of isomers having known relative stereochemistry, for example… In cases where an enantiomer and / or diastereomer exists in a given structure, a wedge-shaped or cleaving bond bearing "R", "S", or "abs" indicates that the composition consists of at least 90% by weight of a single enantiomer or diastereomer having a known absolute stereochemistry, for example... .

[0046] In some cases, diastereomeric mixtures are specified using “r” and / or “s” configurations. In such cases, the relative stereochemistry is specified by a lowercase letter (“r” or “s”), and the absolute stereochemistry is specified by an uppercase letter (“R” or “S”).

[0047] As used herein, "disease" refers to a subject's health status in which the subject is unable to maintain homeostasis, and / or in which the subject's health further deteriorates if the disease is not improved. In contrast, "symptom" in a subject refers to a state in which the subject is able to maintain homeostasis, but the subject's health is not as good as it would be without the symptom. A symptom does not necessarily lead to a further decline in the subject's health when left untreated.

[0048] As used herein, the term "subject" (or "patient") includes mammals, such as humans or non-human mammals, that are susceptible to or suffer from the indicated disease or condition. In some embodiments, the subject is a human. In some embodiments, the subject is a companion animal, such as a dog or cat; in some embodiments, the subject is a domestic animal, such as a cow, horse, sheep, goat, or pig; in some embodiments, the subject may be other domesticated and wild animals. A subject who "needs" treatment according to the invention may "have or be suspected of having" the specific disease or condition; may have been positively diagnosed with the disease or condition; or otherwise present a sufficient number of risk factors or combinations of symptoms to allow a medical professional to diagnose the subject with or suspect that the subject has the disease or condition.

[0049] As used herein, the term "therapeuticly effective amount" refers to a quantity of a compound, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing; or a composition comprising a compound, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, which effectively produces a desired therapeutic response in a particular subject in need. Therefore, the term "therapeuticly effective amount" includes a quantity of a compound, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, which, upon administration, induces improvement in the disease or condition to be treated, or is sufficient to prevent or slow the development or progression of said disease or condition, or to a certain extent alleviate one or more symptoms of the disease or condition to be treated in a subject, or kills diseased cells or inhibits the growth of diseased cells (e.g., cancer cells or autophagy-dependent disease cells), or reduces the amount of at least one of PIP4K2A, PIP4K2B, and PIP4K2C in diseased cells (e.g., reduces the amount of at least PIP4K2C).

[0050] As used herein, the term “neurodegenerative diseases and conditions” refers to disorders characterized by progressive degeneration and / or death of nerve cells, including motor or mental functioning problems. Representative examples include Alzheimer’s disease (AD) and related dementias, Parkinson’s disease (PD) and related dementias, prion disease, motor neuron disease (MND), Huntington’s disease (HD), Pick’s syndrome, spinocerebellar ataxia (SCA), spinal muscular atrophy (SMA), primary progressive aphasia (PPA), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), multiple sclerosis (MS), and other dementias (e.g., vascular dementia (VaD), Lewy body dementia (LBD), semantic dementia, and frontotemporal dementia (FTD)).

[0051] As used herein, the term "autoimmune disease" refers to a disorder in which the immune system produces antibodies that attack normal body tissues. Representative examples of autoimmune diseases include, but are not limited to, autoimmune blood disorders (such as hemolytic anemia, aplastic anemia, anhidrotic ectodermal dysplasia, pure red cell anemia, and idiopathic thrombocytopenic purpura), Sjogren's syndrome, Hashimoto's thyroiditis, rheumatoid arthritis, juvenile (type 1) diabetes, polymyositis, scleroderma, and Addison's disease. Lupus (a disease) includes systemic lupus erythematosus, vitiligo, pernicious anemia, glomerulonephritis, pulmonary fibrosis, celiac disease, polymyalgia rheumatica, multiple sclerosis, ankylosing spondylitis, alopecia areata, vasculitis, autoimmune uveitis, lichen planus, pemphigus, pemphigus vulgaris, phyllodes disease, paraneoplastic pemphigus, myasthenia gravis, immunoglobulin A nephropathy, Wegener's granulomatosis, autoimmune oophoritis, sarcoidosis, rheumatic carditis, ankylosing spondylitis, Graves' disease, autoimmune thrombocytopenic purpura, psoriasis, psoriatic arthritis, herpetic dermatitis, ulcerative colitis, and temporal arteritis, etc.

[0052] As used in this article, the term "cell proliferation disorder or condition" refers to a disorder characterized by disordered or abnormal cell growth or both, including non-cancerous conditions such as cysts, precancerous conditions, benign tumors, and cancer.

[0053] As used herein, “hematologic proliferative disorders or conditions” include lymphoma, leukemia, myeloid sarcoma, mast cell sarcoma, spinal dysplasia, benign monoclonal gammopathy, lymphomatoid papulosis, polycythemia vera, chronic myeloid leukemia, myeloid metaplasia of unknown etiology, and essential thrombocythemia. Therefore, representative examples of hematologic malignancies may include multiple myeloma, lymphomas (including T-cell lymphoma, Hodgkin's lymphoma), non-Hodgkin's lymphoma (diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and ALK+ degenerative large cell lymphoma (e.g., selected from diffuse large B-cell lymphoma (e.g., germinal center B-cell-like diffuse large B-cell lymphoma or activated B-cell-like diffuse large B-cell lymphoma), Burkitt's lymphoma), and other hematologic malignancies. Lymphoma / leukemia, mantle cell lymphoma, mediastinal (thymic) large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma / Waldenstrom macroglobulinemia, metastatic pancreatic adenocarcinoma, refractory B-cell non-Hodgkin lymphoma and relapsed B-cell non-Hodgkin lymphoma, childhood lymphoma and lymphomas of lymphocyte and skin origin, such as small lymphocytic lymphoma, leukemia including childhood leukemia, hairy cell leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, acute myeloid leukemia (e.g., acute monocytic leukemia), chronic lymphocytic leukemia, small lymphocytic leukemia, chronic myeloid leukemia, chronic myeloid leukemia and mast cell leukemia, myeloid sarcoma and mast cell sarcoma.

[0054] As used herein, “cell proliferative disorders or lesions of the liver” includes all forms of cell proliferative disorders affecting the liver. Cell proliferative disorders of the liver can include liver cancer (e.g., hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and hepatoblastoma), precancerous or precancerous lesions of the liver, benign growths or lesions of the liver, and malignant growths or lesions of the liver, as well as metastatic lesions in other tissues and organs of the body besides the liver. Cell proliferative disorders of the liver can include hepatic hyperplasia, metaplasia, and dysplasia.

[0055] As used herein, “cytoproliferative disorders or lesions of the brain” includes all forms of cytoproliferative disorders affecting the brain. Cytoproliferative disorders of the brain can include brain cancers (e.g., gliomas, glioblastomas, meningiomas, pituitary adenomas, vestibular schwannomas, and primitive neuroectodermal tumors (medulloblastomas)), precancerous or precancerous lesions of the brain, benign growths or lesions of the brain, and malignant growths or lesions of the brain, as well as metastatic lesions in tissues and organs other than the brain. Cytoproliferative disorders or lesions of the brain can include proliferation, metaplasia, and dysplasia of the brain.

[0056] As used herein, “cytoproliferative disorders or lesions of the lung” includes all forms of cytoproliferative disorders affecting lung cells. Cytoproliferative disorders of the lung include lung cancer, precancerous and precancerous lesions of the lung, benign growths or lesions of the lung, lung hyperplasia, metaplasia, and dysplasia, as well as metastatic lesions in tissues and organs other than the lungs. Lung cancer includes all forms of lung cancer, such as malignant pulmonary vesicles, carcinoma in situ, typical carcinoid tumors, and atypical carcinoid tumors. Lung cancer includes small cell lung cancer (“SLCL”), non-small cell lung cancer (“NSCLC”), adenocarcinoma, small cell carcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma. Lung cancer can include “scar carcinoma”, bronchoalveolar carcinoma, giant cell carcinoma, spindle cell carcinoma, and large cell neuroendocrine carcinoma. Lung cancer also includes pulmonary vesicles with histological and ultrastructural heterogeneity (e.g., mixed cell types). In some implementations, the compound treats non-metastatic or metastatic lung cancer (e.g., NSCLC, ALK-positive NSCLC, NSCLC with ROS1 rearrangement, lung adenocarcinoma, and squamous cell lung cancer).

[0057] As used in this article, "cell proliferative disorders or conditions of the colon" includes all forms of cell proliferative disorders affecting colonic cells, including colon cancer, precancerous or precancerous lesions of the colon, adenomatous polyps of the colon, and metachronous lesions of the colon. Colon cancer includes sporadic and hereditary colon cancer, malignant colonic neoplasms, carcinoma in situ, typical and atypical carcinoid tumors, adenocarcinoma, squamous cell carcinoma, and squamous cell carcinoma. Colon cancer can be associated with hereditary syndromes such as hereditary nonpolyposis colorectal cancer, common adenomatous polyposis, MYH-associated polyposis, Gardner's syndrome, Peutz-Jeghers syndrome, Turcot's syndrome, and juvenile polyposis. Cell proliferative disorders of the colon are also characterized by hyperplasia, metaplasia, or dysplasia of the colon.

[0058] As used herein, “cell proliferative disorders or lesions of the pancreas” includes all forms of cell proliferative disorders affecting pancreatic cells. Cell proliferative disorders of the pancreas can include pancreatic cancer, precancerous or precancerous lesions of the pancreas, pancreatic hyperplasia, pancreatic dysplasia, benign growths or lesions of the pancreas, and malignant growths or lesions of the pancreas, as well as metastatic lesions in tissues and organs other than the pancreas. Pancreatic cancer includes all forms of pancreatic cancer, including ductal adenocarcinoma, adenosquamous carcinoma, pleomorphic giant cell carcinoma, mucinous adenocarcinoma, osteoclast-like giant cell carcinoma, mucinous cystadenocarcinoma, acinar carcinoma, unclassified large cell carcinoma, small cell carcinoma, pancreatoblastoma, papillary cystadenoma, mucinous cystadenoma, papillary cystadenoma, and serous cystadenoma, as well as pancreatic cystadenoma with histological and ultrastructural heterogeneity (e.g., mixed cell).

[0059] As used herein, “proliferative disorders or lesions of the prostate” includes all forms of proliferative disorders affecting the prostate. Proliferative disorders of the prostate can include prostate cancer, precancerous or precancerous lesions of the prostate, benign growths or lesions of the prostate and malignant growths or lesions of the prostate, as well as metastatic lesions in tissues and organs other than the prostate in the body. Proliferative disorders of the prostate can include hyperplasia, metaplasia, and dysplasia of the prostate.

[0060] As used herein, “cytoproliferative disorders or conditions of the ovary” includes all forms of cytoproliferative disorders affecting the ovary. Cytoproliferative disorders of the ovary can include precancerous or precancerous lesions of the ovary, benign growths or lesions of the ovary, ovarian cancer, and metastatic lesions in tissues and organs other than the ovary. Cytoproliferative disorders of the ovary can include ovarian hyperplasia, metaplasia, and dysplasia.

[0061] As used herein, "a proliferative disorder or condition of the breast" includes all forms of proliferative disorders affecting breast cells. Proliferative disorders of the breast can include breast cancer, precancerous or precancerous lesions of the breast, benign growths or lesions of the breast, and metastatic lesions in tissues and organs other than the breast. Proliferative disorders of the breast can include hyperplasia, metaplasia, and dysplasia of the breast.

[0062] As used herein, "cell proliferation disorders or conditions of the skin" includes all forms of cell proliferation disorders affecting skin cells. Cell proliferation disorders of the skin can include precancerous or precancerous lesions of the skin, benign growths or lesions of the skin, melanoma, malignant melanoma, or other malignant growths or lesions of the skin, as well as metastatic lesions in tissues and organs other than the skin. Cell proliferation disorders of the skin can include hyperplasia, metaplasia, and dysplasia of the skin.

[0063] As used herein, "endometrial proliferative disorders or conditions" encompasses all forms of proliferative disorders affecting endometrial cells. Endometrial proliferative disorders can include precancerous or precancerous lesions of the endometrium, benign growths or abnormalities of the endometrium, endometrial cancer, and metastatic lesions in tissues and organs other than the endometrium. Endometrial proliferative disorders can include endometrial hyperplasia, metaplasia, and dysplasia.

[0064] In some implementations, the cancer is a blood cancer, such as leukemia, lymphoma, or multiple myeloma.

[0065] Compound of formula (I') or (I) In one aspect, a compound of formula (I') is provided. (I'), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C(O)O-#, -OC(O)# -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-OC(O)N(R V )-#、-N(R V -C(O)O#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Q is R Q Or ring 5, Among them, ring 5 is selected from the following groups: arbitrarily selected by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally with one or more R 5b Substituted 5- to 12-membered heteroaryl groups; or Q has the formula (i) , (i) in: Ring A can be selected from the following groups: , , and Each of them is optionally controlled by one or more Cs 1-4 Alkyl or halogenated groups; X is a bond, -O-, -NH-, or -NHC(O)-; Ring B can be selected from the following groups: , , , , , and Each of them is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4 Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a bond, -O-, -NH-, or -NHC(O)-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. C Substituted 4- to 12-membered heterocyclic groups; The connectors are key, -O-, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**,in *Indicates the connection point with ring C when ring C exists, and *Indicates the connection point with W when ring C does not exist; and **Indicates the connection point with U when ring 2 exists, and** indicates the connection point with V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ); When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a bond or C(O); Ring 2 is optional, and when present, is selected from the following groups: optionally by one or more R... 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The 6 to 12 aryl groups are replaced, and optionally by one or more R groups. 2b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C 1-4 Hydroxyalkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R w Independently a 3- to 10-membered cycloalkyl group, optionally substituted with a halogen group, or optionally substituted with a hydroxyl group, C 1-4 Hydroxyalkyl or C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl, 3- to 10-membered cycloalkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic lactam, or (b) V contains amides or carbamates, or (c) V together with the atoms of the ring 1, ring 2 or ring 5 to which it is attached forms an amide or carbamate; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 exists and is not a cycloalkyl or tetrahydropyranyl group; And among them: When ring 1 is an 8-membered heterocyclic group, ring 3 is a CN-substituted phenyl group, ring 4 is absent, and Q is R. Q And when V is -OC(O)#, then R Q Not schuding.

[0066] In one aspect, a compound of formula (I') is provided. (I'), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C(O)O-#, -OC(O)# -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-OC(O)N(R V )-#、-N(R V -C(O)O#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Q is R Q Or ring 5, Among them, ring 5 is selected from the following groups: arbitrarily selected by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally with one or more R 5b Substituted 5- to 12-membered heteroaryl groups; or Q has the formula (i) , (i) in: Ring A can be selected from the following groups: , , and Each of them is optionally controlled by one or more Cs 1-4 Alkyl or halogenated groups; X is a bond, -O-, -NH-, or -NHC(O)-; Ring B can be selected from the following groups: , , , , , and Each of them is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4 Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a bond, -O-, -NH-, or -NHC(O)-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. CSubstituted 4- to 12-membered heterocyclic groups; The connectors are key, -O-, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**,in *Indicates the connection point with ring C when ring C exists, and *Indicates the connection point with W when ring C does not exist; and **Indicates the connection point with U when ring 2 exists, and** indicates the connection point with V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ); When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a bond or C(O); Ring 2 is optional, and when present, is selected from the following groups: optionally by one or more R... 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The 6 to 12 aryl groups are replaced, and optionally by one or more R groups. 2b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) nR x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C 1-4 Hydroxyalkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R w Independently a 3- to 10-membered cycloalkyl group, optionally substituted with a halogen group, or optionally substituted with a hydroxyl group, C 1-4 Hydroxyalkyl or C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl, 3- to 10-membered cycloalkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic lactam, or (b) V contains amides or carbamates, or (c) V together with the atoms of the ring 1, ring 2 or ring 5 to which it is attached forms an amide or carbamate; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group.

[0067] In one aspect, a compound of formula (I) is provided: (I), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 Substitution, wherein each 4- to 8-membered heterocyclic group of ring 1 contains at least one heteroatom selected from N and O; V is a key, -C 1-4 Alkylene-, -C(O)-, -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Q is R Q Or ring 5, Among them, ring 5 is selected from the following groups: arbitrarily selected by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally with one or more R 5b Replaced 5 to 12 heteroaryl groups, or Q has the formula (i) , (i) in: Ring A can be selected from the following groups: , , and Each of them is optionally controlled by one or more Cs 1-4 Alkyl or halogenated groups; X is a bond, -O-, -NH-, or -NHC(O)-; Ring B can be selected from the following groups: , , , , , and Each of them is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4 Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a bond, -O-, -NH-, or -NHC(O)-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. C Substituted 4- to 12-membered heterocyclic groups; The connector is a key, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**,in *Indicates the connection point with ring C when ring C exists, and *Indicates the connection point with W when ring C does not exist; and **Indicates the connection point with U when ring 2 exists, and** indicates the connection point with V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ); When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a bond or C(O); Ring 2 is optional, and when present, is selected from the following groups: optionally by one or more R... 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The 6 to 12 aryl groups are replaced, and optionally by one or more R groups. 2b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y)-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic lactam, or (b) V contains amides, or (c) V together with the atoms of ring 1, ring 2 or ring 5 to which it is attached forms an amide; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 exists and is not a cycloalkyl or tetrahydropyranyl group; And among them: When ring 1 is an 8-membered heterocyclic group, ring 3 is a CN-substituted phenyl group, ring 4 is absent, and Q is R. Q And when V is -OC(O)#, then R Q Not schuding.

[0068] In one aspect, a compound of formula (I) is provided: (I), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 Substitution, wherein each 4- to 8-membered heterocyclic group of ring 1 contains at least one heteroatom selected from N and O; V is a key, -C 1-4 Alkylene-, -C(O)-, -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Q is R Q Or ring 5, Among them, ring 5 is selected from the following groups: arbitrarily selected by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally with one or more R 5b Replaced 5 to 12 heteroaryl groups, or Q has the formula (i) , (i) in: Ring A can be selected from the following groups: , , and Each of them is optionally controlled by one or more Cs 1-4 Alkyl or halogenated groups; X is a bond, -O-, -NH-, or -NHC(O)-; Ring B can be selected from the following groups: , , , , , and Each of them is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4 Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a bond, -O-, -NH-, or -NHC(O)-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. C Substituted 4- to 12-membered heterocyclic groups; The connector is a key, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**,in *Indicates the connection point with ring C when ring C exists, and *Indicates the connection point with W when ring C does not exist; and **Indicates the connection point with U when ring 2 exists, and** indicates the connection point with V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ); When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a bond or C(O); Ring 2 is optional, and when present, is selected from the following groups: optionally by one or more R... 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The 6 to 12 aryl groups are replaced, and optionally by one or more R groups. 2b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic amide, or (b) V contains amides, or (c) V together with the atoms of ring 1, ring 2 or ring 5 to which it is attached forms an amide; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group.

[0069] In one aspect, a compound of formula (I) is provided: (I), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group, a saturated 4- to 8-membered heterocyclic group comprising at least one cyclic ether or cyclic amine, or a saturated 4- to 8-membered heterocyclic group comprising a cyclic amide, each optionally being construed with one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1, and Q is R Q Or ring 5, Among them, ring 5 is selected from the following groups: arbitrarily selected by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally with one or more R 5b Replaced 5 to 12 heteroaryl groups, or Q has the formula (i) , (i) in: Ring A can be selected from the following groups: , , and Each of them is optionally controlled by one or more Cs 1-4 Alkyl or halogenated groups; X is a bond, -O-, -NH-, or -NHC(O)-; Ring B can be selected from the following groups: , , , , , and Each of them is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4 Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a bond, -O-, -NH-, or -NHC(O)-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. C Substituted 4- to 12-membered heterocyclic groups; The connector is a key, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**,in *Indicates the connection point with ring C when ring C exists, and *Indicates the connection point with W when ring C does not exist; and **Indicates the connection point with U when ring 2 exists, and** indicates the connection point with V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ); When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a bond or C(O); Ring 2 is optional, and when present, is selected from the following groups: optionally by one or more R... 2aThe substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The 6 to 12 aryl groups are replaced, and optionally by one or more R groups. 2b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (i) When ring 1 is optionally bounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amine, then V is attached to the cyclic nitrogen atom of ring 1 and is -C(O)- or -C. 1-4 alkylene-C(O)-#; and (ii) When ring 1 is optionally bounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amide, then V is attached to the cyclic nitrogen atom of ring 1 and is a bond or -C. 1-4 alkylene-; and (iii) When ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1 When replacing, then: (a) V is -C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#; or (b) Ring 5 is optionally bounded by one or more R 5a Substituted 4- to 12-membered heterocyclic groups, where V is -C(O)- and attached to a cyclic nitrogen atom in ring 5; or (c) Ring 2 is optionally bounded by one or more R 2a Substituted 4- to 12-membered heterocyclic groups, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 2; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group.

[0070] In one aspect, a compound of formula (I) is provided: (I), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 Substitution, wherein each 4- to 8-membered heterocyclic group of ring 1 contains at least one N heteroatom; V is -C(O)-, -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-# or -C 1-4 Alkylene-C(O)N(R) V )-#, where # indicates the connection point with ring 1; and Q is R Q , or Q has the formula (i) , (i) in: Ring A is Optionally by one or more C 1-4 Alkyl or halogenated groups; X is a bond or -NH-; Ring B is free to choose , and The group consists of groups, each of which is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4 Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a key or -O-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. C Substituted 6-membered heterocyclic group; The connector is a key, C 1-10 Alkylene or C(O)C 1-10 Alkylene; When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a key; Ring 2 is optional, and when present, is optionally bounded by one or more R's. 2a Substituted 6- or 11-membered heterocyclic groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a and R 4a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 3b and R 4b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C1-4 Halogenated groups; Each R V Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (i) When ring 1 is optionally bounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amine, then V is attached to the cyclic nitrogen atom of ring 1 and is -C(O)- or -C. 1-4 alkylene-C(O)-#; and (ii) When ring 1 is optionally bounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amide, then V is attached to the nitrogen atom of the cyclic amide in ring 1 and is a bond or -C. 1-4 alkylene-; and (iii) When ring 1 is optionally bounded by one or more R 1 Replacement C 4-8 When cycloalkyl is used, then: (a) V is -C(O)N(R) V -# or -N(R) V )C(O)-#; or (b) Ring 2 is optionally bounded by one or more R 2a A substituted 6- or 11-membered heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 2; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group.

[0071] In some embodiments of the compound of formula (I), R is chlorine, fluorine, or bromine.

[0072] In some embodiments of the compound of formula (I), ring 1 is optionally surrounded by one or more R 1 Replacement C 4-8 cycloalkyl, wherein each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl group. In some embodiments, ring 1 is optionally surrounded by one or more R groups. 1 Replacement C 5-8 Cycloalkyl. In some embodiments, ring 1 is optionally surrounded by one or more R... 1 Replacement C 6-8 Cycloalkyl. In some embodiments, ring 1 is cyclohexyl or spiro[3.3.]heptyl, each optionally distilled by one or more R... 1 Replacement. In some implementations, ring 1 is... or Each of them is optionally controlled by one or more R1 Replacement. In some implementations, ring 1 is... , or Each of them is optionally controlled by one or more R 1 Replacement. In some implementations, ring 1 is... In some implementations, ring 1 is... In some implementations, ring 1 is... .

[0073] In some implementation schemes, ring 1 is or In some implementations, ring 1 is... In some implementations, ring 1 is... .

[0074] In some embodiments of the compound of formula (I), ring 1 is a saturated 4- to 8-membered heterocyclic group comprising at least one cyclic ether or cyclic amine, optionally surrounded by one or more R groups. 1 Replace, where each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl group. In some embodiments of compounds of formula (I), ring 1 is a saturated 5- to 8-membered heterocyclic group comprising at least one cyclic ether or cyclic amine, optionally surrounded by one or more R groups. 1 Substitution. In some embodiments of compounds of formula (I), ring 1 is a saturated 6- to 8-membered heterocyclic group comprising at least one cyclic ether or cyclic amine, optionally replaced by one or more R... 1Substitution. In some embodiments, ring 1 is piperidinyl or 2-azaspiro[3.3]heptyl, each optionally replaced by one or more R 1 Replacement. In some implementations, ring 1 is... or The # symbol is connected to V, each of which is optionally linked to one or more R symbols. 1 Replacement. In some implementations, ring 1 is... , or The # symbol is connected to V, each of which is optionally linked to one or more R symbols. 1 Replacement. In some implementations, ring 1 is... In some implementations, ring 1 is... In some implementations, ring 1 is... .

[0075] In some embodiments of the compound of formula (I), ring 1 is a saturated 4- to 8-membered heterocyclic group comprising a cyclic amide, optionally surrounded by one or more R 1 Replace, where each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl group. In some embodiments, ring 1 is... Optionally by one or more R 1 Instead, where # indicates a connection to V. In some implementations, ring 1 is... or Each of them is optionally controlled by one or more R 1 Replacement. In some implementations, ring 1 is... In some implementations, ring 1 is... .

[0076] In some embodiments of the compound of formula (I), ring 1 is optionally surrounded by one or more R 1 Replacement C 4-8 cycloalkyl, wherein each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##, where ## indicates a connection to ring 1. In some embodiments, ring 1 is optionally connected to one or more R 1 Replacement C 5-8 Cycloalkyl, and V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is optionally bounded by one or more R 1 Replacement C 6-8 Cycloalkyl, and V is -C(O)N(R) V)-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some embodiments, ring 1 is cyclohexyl or spiroheptyl, each optionally distilled by one or more R 1 Replacement, and V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is or Each of them is optionally controlled by one or more R 1 Replacement, and V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is , or Each of them is optionally controlled by one or more R 1 Replacement, and V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is And V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is And V is -C(O)N(R) V )-##、-N(R V)C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is And V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##.

[0077] In some embodiments of the compound of formula (I), ring 1 is optionally surrounded by one or more R 1 Replacement C 4-8 cycloalkyl, wherein each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl group; and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V)C(O)-##, where ## indicates a connection to ring 1. In some embodiments, ring 1 is optionally connected to one or more R 1 Replacement C 5-8 Cycloalkyl, and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is optionally bounded by one or more R 1 Replacement C 6-8 Cycloalkyl, and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some embodiments, ring 1 is cyclohexyl or spiroheptyl, each optionally distilled by one or more R 1 Replacement, and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is , , or Each of them is optionally controlled by one or more R 1 Replacement, and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is , , , or Each of them is optionally controlled by one or more R 1 Replacement, and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is And V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is And V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is And V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is And V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some implementations, ring 1 is And V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##.

[0078] In some embodiments of the compound of formula (I), ring 1 is a 4- to 8-membered heterocyclic ring comprising at least one cyclic ether and not comprising a cyclic amine or cyclic amide, optionally surrounded by one or more R 1 Replace, where each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some embodiments, ring 1 is a 5- to 8-membered heterocyclic ring that does not contain cyclic amines or cyclic amides, optionally surrounded by one or more R 1 Replacement, and V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some embodiments, ring 1 is a 6- to 8-membered heterocyclic ring that does not contain a cyclic amine or cyclic amide, optionally surrounded by one or more R 1 Replacement, and V is -C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##.

[0079] In some embodiments of the compound of formula (I), ring 1 is a 4- to 8-membered heterocyclic ring comprising at least one cyclic ether and not comprising a cyclic amine or cyclic amide, optionally surrounded by one or more R 1 Replace, where each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y(R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl group; and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some embodiments, ring 1 is a 5- to 8-membered heterocyclic ring that does not contain cyclic amines or cyclic amides, optionally surrounded by one or more R 1 Replacement, and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##. In some embodiments, ring 1 is a 6- to 8-membered heterocyclic ring that does not contain a cyclic amine or cyclic amide, optionally surrounded by one or more R 1 Replacement, and V is -OC(O)N(R) V )-##、-N(R V -C(O)O##、-C(O)N(R) V )-##、-N(R V )C(O)-##、-C 1-4 Alkylene-C(O)N(R) V -## or -C 1-4 Alkylene-N(R) V )C(O)-##.

[0080] In some embodiments of the compound of formula (I), ring 1 is a saturated 4- to 8-membered heterocyclic group comprising at least one cyclic amine and not a cyclic amide, optionally surrounded by one or more R 1 Replace, where each R 1Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and V is -C(O)-## or -C 1-4 Alkylene-C(O)-##, where ## indicates attachment to ring 1. In some embodiments of compounds of formula (I), ring 1 is a saturated 5- to 8-membered heterocyclic group comprising at least one cyclic amine, optionally connected by one or more R 1 Replacement, and V is -C(O)-## or -C 1-4 Alkylene-C(O)-##, where ## indicates attachment to ring 1. In some embodiments of compounds of formula (I), ring 1 is a saturated 6- to 8-membered heterocyclic group comprising at least one cyclic amine, optionally connected by one or more R 1 Replace, and V is -C(O)-## or -C 1-4 Alkylene-C(O)-##, where ## indicates attachment to ring 1. In some embodiments, ring 1 is piperidinyl or 2-azaspiro[3.3]heptyl, each optionally linked by one or more R 1 Replace, and V is -C(O)-## or -C 1-4 Alkylene-C(O)-##, where ## indicates attachment to ring 1. In some embodiments, ring 1 is... or Each of them is optionally controlled by one or more R 1 Replace, where # indicates connection to V; and V is -C(O)-## or -C 1-4 Alkylene-C(O)-##. In some embodiments, ring 1 is... , or Each of them is optionally controlled by one or more R 1 Replace, and V is -C(O)-## or -C 1-4 Alkylene-C(O)-##. In some embodiments, ring 1 is... And V is -C(O)-## or -C 1-4 Alkylene-C(O). In some embodiments, ring 1 is... And V is -C(O)-## or -C 1-4 Alkylene-C(O). In some embodiments, ring 1 is... And V is -C(O)-## or -C 1-4 Alkylene-C(O).

[0081] In some embodiments of the compound of formula (I), ring 1 is a saturated 4- to 8-membered heterocyclic group comprising at least one cyclic amine and not a cyclic amide, optionally surrounded by one or more R 1 Replace, where each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and V is -C(O)O-##, -OC(O)##, -C(O)-## or -C 1-4 Alkylene-C(O)-##, where ## indicates attachment to ring 1. In some embodiments of compounds of formula (I), ring 1 is a saturated 5- to 8-membered heterocyclic group comprising at least one cyclic amine, optionally connected by one or more R 1 Replace, and V is -C(O)O-##, -OC(O)##, -C(O)-## or -C 1-4Alkylene-C(O)-##, where ## indicates attachment to ring 1. In some embodiments of compounds of formula (I), ring 1 is a saturated 6- to 8-membered heterocyclic group comprising at least one cyclic amine, optionally connected by one or more R 1 Replace, and V is -C(O)O-##, -OC(O)##, -C(O)-## or -C 1-4 Alkylene-C(O)-##, where ## indicates attachment to ring 1. In some embodiments, ring 1 is piperidinyl or 2-azaspiro[3.3]heptyl, each optionally linked by one or more R 1 Replace, and V is -C(O)O-##, -OC(O)##, -C(O)-## or -C 1-4 Alkylene-C(O)-##, where ## indicates attachment to ring 1. In some embodiments, ring 1 is... or Each of them is optionally controlled by one or more R 1 Replace, where # indicates connection to V; and V is -OC(O)##, -C(O)-##, or -C 1-4 Alkylene-C(O)-##. In some embodiments, ring 1 is... , or Each of them is optionally controlled by one or more R 1 Replace, and V is -OC(O)##, -C(O)-##, or -C 1-4 Alkylene-C(O)-##. In some embodiments, ring 1 is... And V is -OC(O)##, -C(O)-## or -C 1-4 Alkylene-C(O). In some embodiments, ring 1 is... And V is -OC(O)##, -C(O)-## or -C 1-4 Alkylene-C(O). In some embodiments, ring 1 is... And V is -OC(O)##, -C(O)-## or -C 1-4 Alkylene-C(O).

[0082] In some embodiments of the compound of formula (I), ring 1 is a saturated 4- to 8-membered heterocyclic group comprising a cyclic amide, optionally surrounded by one or more R 1 Replacement, and V is a key or -C 1-4 Alkylene-. In some embodiments, ring 1 is... Optionally by one or more R 1 Replace, where # indicates concatenation with V; and V is a key or -C 1-4 Alkylene-. In some embodiments, ring 1 is... or Each of them is optionally controlled by one or more R 1 Replacement; and V is a bond or -C 1-4 Alkylene-. In some embodiments, ring 1 is... And V is a key or -C 1-4 Alkylene-. In some embodiments, ring 1 is... And V is a key or -C 1-4 Alkylene-.

[0083] In some embodiments, ring 1 comprises a cyclic lactam, or V comprises an amide, or V, together with the atoms of ring 1, ring 2, or ring 5 to which it is attached, forms an amide. In some embodiments, ring 1 comprises a cyclic lactam. In some embodiments, V comprises an amide. In some embodiments, V, together with the atoms of ring 1, ring 2, or ring 5 to which it is attached, forms an amide. In some embodiments of formula (I), (II), (III), or (IV), or appropriate related formulas, V, together with the atoms of ring 1 to which it is attached, forms an amide. In some embodiments of formula (I), (II), or appropriate related formulas, V, together with the atoms of ring 5 to which it is attached, forms an amide. In some embodiments of formula (I), (IV), or appropriate related formulas, V, together with the atoms of ring 5 to which it is attached, forms an amide.

[0084] In some embodiments, V comprises a urethane ester, or V forms a urethane ester together with atoms of the ring 1, ring 2, or ring 5 to which it is attached. In some embodiments, V comprises a urethane ester. In some embodiments, V forms a urethane ester together with atoms of the ring 1, ring 2, or ring 5 to which it is attached. In some embodiments of formula (I'), (I), (II), (III), or (IV), or appropriate related formulas, V forms a urethane ester together with atoms of the ring 1 to which it is attached. In some embodiments of formula (I'), (I), or (II), or appropriate related formulas, V forms a urethane ester together with atoms of the ring 5 to which it is attached. In some embodiments of formula (I'), (I), or (IV), or appropriate related formulas, V forms a urethane ester together with atoms of the ring 5 to which it is attached.

[0085] In some implementations, when ring 1 is optionally surrounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amine, then V is attached to the cyclic nitrogen atom of ring 1 and is -C(O)- or -C. 1-4 Alkylene-C(O)-#.

[0086] In some implementations, when ring 1 is optionally surrounded by one or more R 1When the substituted ring is a 4- to 8-membered heterocyclic ring containing at least one cyclic amine, then V is attached to the cyclic nitrogen atom of ring 1 and is -OC(O)##.

[0087] In some implementations, when ring 1 is optionally surrounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amide, then V is attached to the cyclic nitrogen atom of ring 1 and is a bond or -C. 1-4 Alkylene-.

[0088] In some implementations, when ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1 When substituted, then (a) V is -C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V (a)C(O)-#; or (b)ring 5 is optionally bounded by one or more R 5a The substituted 4- to 12-membered heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 5; or (c) ring 2 is optionally occupied by one or more R groups. 2a The substituted 4 to 12-membered heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2.

[0089] In some implementations, when ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1 When substituted, then (a) V is -OC(O)N(R) V -# or -N(R) V (a)-C(O)O#, where # indicates connection to ring 1; or (b) ring 5 is optionally connected to one or more R 5a The substituted 4- to 12-membered heterocyclic group, and V is -C(O)O-# and attached to a cyclic nitrogen atom in ring 5, where # indicates attachment to ring 1; or (c) ring 2 is optionally occupied by one or more R 2a The substituted 4 to 12-membered heterocyclic group, and V is -C(O)O-# and attached to the cyclic nitrogen atom of ring 2, where # indicates attachment to ring 1.

[0090] In some implementations, when ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1When substituted, V becomes -C(O)N(R). V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#.

[0091] In some implementations, when ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1 When substituted, V becomes -OC(O)N(R) V -# or -N(R) V )-C(O)O#, where # indicates connection to ring 1.

[0092] In some implementations, when ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1 When replaced, ring 5 is optionally replaced by one or more R 5a The substituted 4 to 12-membered heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 5.

[0093] In some implementations, when ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1 When replaced, ring 5 is optionally replaced by one or more R 5a The substituted 4 to 12-membered heterocyclic group, and V is -C(O)O-# and attached to the cyclic nitrogen atom of ring 5, where # indicates attachment to ring 1.

[0094] In some implementations, when ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1 When replaced, ring 2 is optionally replaced by one or more R 2a The substituted 4 to 12-membered heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2.

[0095] In some implementations, when ring 1 is C 4-8 Cycloalkyl or 4- to 8-membered heterocyclic rings that do not contain cyclic amines or cyclic amides, each optionally surrounded by one or more R 1 When replaced, ring 2 is optionally replaced by one or more R 2aThe substituted 4 to 12-membered heterocyclic group, and V is -C(O)O-# and attached to the cyclic nitrogen atom of ring 2, where # indicates attachment to ring 1.

[0096] In some embodiments of the compound of formula (I), the compound has the formulas (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw):

[0097] Q, R, ring 3, and ring 4 are as defined herein with respect to equation (I). In some implementations, ring 4 is present.

[0098] In some embodiments of the compound of formula (I), the compound has the formulas (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), and (I-ag):

[0099] Q, R, ring 3, and ring 4 are as defined herein with respect to equation (I). In some implementations, ring 4 is present.

[0100] In some embodiments of compounds of formula (I) or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), ring 3 is optionally surrounded by one or more R 3b The substituted phenyl group, and ring 4 is optionally replaced by one or more R groups. 4b Substituted phenyl groups. In some embodiments, the compound has the formula (Ix). (Ix), or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein each m is independently an integer from 0 to 4, and Q, V, R, and ring 1 are as described herein with respect to formula (I). In some embodiments, each m is independently an integer from 0 to 2. In some embodiments, each m is 0 or 1. In some embodiments, ring 3 is phenyl, ring 4 is phenyl, and the compound has formula (Iy). (Iy), or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein Q, V, R, and ring 1 are as described herein with respect to formula (I). In some embodiments of formula (Ix) or (Iy), ring 1 is cyclohexyl or piperidinyl, each optionally separated by one or more R 1 Replacement. In some embodiments, ring 1 is cyclohexyl or piperidinyl, each optionally replaced by one or more R... 1 Substitution, and Q has formula (i). In some embodiments, ring 1 is cyclohexyl or piperidinyl, each optionally replaced by one or more R 1 Replace, and Q is R Q .

[0101] In some embodiments, ring 3 is a 5-membered heteroaryl group, and ring 4 is present. In some embodiments, ring 3 is a 5-membered heteroaryl group, and ring 4 is not a cycloalkyl or tetrahydropyranyl group. In some embodiments, ring 3 is a 5-membered heteroaryl group, and ring 4 is optionally surrounded by one or more R groups. 4b Substituted phenyl, optionally with one or more R 4b The substituted 5 to 6 heteroaryl groups or optionally one or more R 4a The substituted 4- to 6-membered heterocyclic group, wherein ring 4 is not tetrahydropyranyl. In some embodiments, ring 3 is a 5-membered heteroaryl group, and ring 4 is optionally replaced by one or more R groups. 4b Substituted phenyl or optionally with one or more R 4b The substituted 5- to 6-membered heteroaryl group. In some embodiments, ring 3 is a 5-membered heteroaryl group, and ring 4 is optionally replaced by one or more R groups. 4a Substituted 4- to 6-membered heterocyclic groups, wherein ring 4 is not a tetrahydropyranyl group.

[0102] In some embodiments of compounds of formula (I) or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), ring 3 is optionally surrounded by one or more R 3a The substituted 5- or 6-membered heterocyclic group and ring 4 is optionally replaced by one or more R groups. 4b Substituted phenyl groups.

[0103] In some embodiments of compounds of formula (I) or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), ring 3 is optionally surrounded by one or more R 3a The substituted 5- or 6-membered heterocyclic group and ring 4 is optionally replaced by one or more R groups. 4b Substituted 5- or 6-membered heteroaryl groups.

[0104] In some embodiments of compounds of formula (I) or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), ring 3 is optionally surrounded by one or more R 3b The substituted phenyl group, and ring 4 is optionally replaced by one or more R groups. 4a Substituted 5- or 6-membered heterocyclic groups.

[0105] In some embodiments of compounds of formula (I) or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), ring 3 is optionally surrounded by one or more R 3b The substituted phenyl group, and ring 4 is optionally replaced by one or more R groups. 4a Substituted 3- to 6-membered cycloalkyl groups.

[0106] In some embodiments of compounds of formula (I) or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), ring 3 is optionally surrounded by one or more R 3b The substituted 5- or 6-membered heteroaryl group, and ring 4 is optionally replaced by one or more R groups. 4b Substituted phenyl groups.

[0107] In some embodiments of compounds of formula (I) or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), and (Iy), Q is H.

[0108] In some embodiments of compounds of formula (I) or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), and (Iy), Q is R Q In some implementations, R Q H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups. In some embodiments, R Q Halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups. In some embodiments, R Q C 1-4 Alkyl or C 1-4 Halogenated groups. In some embodiments, R Q C 1-2 Alkyl or C 1-2 Halogenated groups. In some embodiments, R Q It is methyl. In some embodiments, R Q For H.

[0109] In some embodiments of the compound of formula (I), Q is ring 5, and the compound has formula (II). (II), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein rings 5, V, 1, R, 3, and 4 are as described with respect to formula (I). In some embodiments, ring 4 is present.

[0110] In some embodiments of the compound of formula (I), Q is ring 5, and the compound has formula (II). (II), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C(O)O-#, -OC(O)# -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-OC(O)N(R V )-#、-N(R V -C(O)O#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Ring 5 can be freely grouped into the following groups: optionally by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally with one or more R 5b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C1-4 Alkyl, C(O)R w C 1-4 Hydroxyalkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R V Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R w Independently a 3- to 10-membered cycloalkyl group, optionally substituted with a halogen group, or optionally substituted with a hydroxyl group, C 1-4 Hydroxyalkyl or C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4Alkyl, 3- to 10-membered cycloalkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic amide, or (b) V contains amides or carbamates, or (c) V together with the atoms of the ring 1 or ring 5 to which it is attached forms an amide or carbamate; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group.

[0111] In some embodiments of the compound of formula (I), Q is R Q Furthermore, the compound has formula (III). (III), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C(O)O-#, -OC(O)# -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-OC(O)N(R V)-#、-N(R V -C(O)O#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C 1-4 Hydroxyalkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R w Independently a 3- to 10-membered cycloalkyl group, optionally substituted with a halogen group, or optionally substituted with a hydroxyl group, C 1-4 Hydroxyalkyl or C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl, 3- to 10-membered cycloalkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic lactam, or (b) V contains amides or carbamates, or (c) V together with the atoms of the ring 1 to which it is attached forms an amide or carbamate; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 exists and is not a cycloalkyl or tetrahydropyranyl group; And among them: When ring 1 is an 8-membered heterocyclic group, ring 3 is a CN-substituted phenyl group, ring 4 is absent, and V is -OC(O)#, then R Q Not schuding.

[0112] In some embodiments of the compound of formula (I), Q is R Q Furthermore, the compound has formula (III). (III), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C(O)O-#, -OC(O)# -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-OC(O)N(R V )-#、-N(R V -C(O)O#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n-C 1-4 alkyl; Each R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C 1-4 Hydroxyalkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R w Independently a 3- to 10-membered cycloalkyl group, optionally substituted with a halogen group, or optionally substituted with a hydroxyl group, C 1-4 Hydroxyalkyl or C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl, 3- to 10-membered cycloalkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic lactam, or (b) V contains amides or carbamates, or (c) V together with the atoms of the ring 1 to which it is attached forms an amide or carbamate; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group.

[0113] In some embodiments of compounds of formula (I) or (II), ring 5 is selected from the group consisting of: optionally being surrounded by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally with one or more R 5b Substituted 5 to 12 heteroaryl groups; wherein each R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxo groups; and each R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x .

[0114] In some embodiments of compounds of formula (I) or (II), ring 5 is optionally surrounded by one or more R 5a Replacement C 3-10 cycloalkyl, wherein each R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or an oxy group. In some embodiments, ring 5 is optionally surrounded by one or more R groups. 5a Replacement C 5-10 cycloalkyl, wherein each R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O)n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or an oxy group. In some embodiments, ring 5 is optionally surrounded by one or more R groups. 5a Replacement C 5-6 cycloalkyl, wherein each R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or an oxy group. In some embodiments, ring 5 is optionally surrounded by one or more R groups. 5a Substituted C6 cycloalkyl groups, wherein each R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y)C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group.

[0115] In some embodiments of compounds of formula (I) or (II), ring 5 is optionally surrounded by one or more R 5a Substituted 4- to 12-membered heterocyclic groups, wherein each R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or an oxy group. In some embodiments, ring 5 is optionally surrounded by one or more R groups. 5a The substituted 5- to 6-membered heterocyclic group. In some embodiments, ring 5 is piperidinyl or piperazine, each optionally replaced by one or more R groups. 5a Replacement. In some implementations, ring 5 is optionally replaced by one or more R 5a The 10- to 12-membered heterocyclic group is replaced. In some embodiments, ring 5 is... , , or Each of them is optionally controlled by one or more R 5a Instead, where # indicates a connection to V. In some implementations, ring 5 is... , , or Each of them is optionally controlled by one or more R 5a Instead, where # indicates a connection to V. In some implementations, ring 5 is... , or Each of them is optionally controlled by one or more R 5a Instead, where # indicates a connection to V. In some implementations, ring 5 is... or In some implementations, ring 5 is... or In some implementations, R 5a C 1-4 Alkyl or C(O)C 1-4 Alkyl group. In some embodiments, R 5a It can be methyl or acetyl.

[0116] In some embodiments of compounds of formula (I) or (II), ring 5 is optionally surrounded by one or more R 5b Substituted 5 to 12 heteroaryl groups, wherein each R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x In some implementations, ring 5 is optionally bounded by one or more R...5b Substituted 5- to 6-membered heteroaryl groups.

[0117] In some implementation schemes, ring 1 is And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 4 is present.

[0118] In some implementation schemes, ring 1 is And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 1 is... And Q is R Q In some implementations, ring 4 is present.

[0119] In some embodiments of compounds of formula (I) or (II), ring 1 is optionally surrounded by one or more R 1 Replacement C 4-8 Cycloalkyl, ring 5 is optionally surrounded by one or more R 5a Substituted 4- to 12-membered heterocyclic groups, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 5, and wherein each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl groups; and each R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C1-4 Alkylene-S(O) n R x Or an oxy group. In some embodiments, ring 1 is optionally surrounded by one or more R groups. 1 Replacement C 5-8 Cycloalkyl, ring 5 is optionally surrounded by one or more R 5a The substituted 4- to 12-membered heterocyclic group, wherein ring 5 comprises at least one N atom, and V is -C(O)- and linked to a cyclic nitrogen atom of ring 5. In some embodiments, ring 1 is optionally separated by one or more R... 1 Replacement C 6-8 Cycloalkyl, ring 5 is optionally surrounded by one or more R 5a The substituted 4- to 12-membered heterocyclic group, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 5. In some embodiments, ring 1 is cyclohexyl or spiroheptyl, each optionally substituted with one or more R 1 Instead, ring 5 is optionally replaced by one or more R 5a A substituted 4- to 12-membered heterocyclic group, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 5. In some embodiments, ring 1 is... or Each of them is optionally controlled by one or more R 1 Instead, ring 5 is optionally replaced by one or more R 5a A substituted 4- to 12-membered heterocyclic group, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 5. In some embodiments, ring 1 is... , or Each of them is optionally controlled by one or more R 1 Instead, ring 5 is optionally replaced by one or more R 5a A substituted 4- to 12-membered heterocyclic group, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 5. In some embodiments, ring 1 is... Ring 5 is optionally occupied by one or more R 5a A substituted 4- to 12-membered heterocyclic group, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 5. In some embodiments, ring 1 is... Ring 5 is optionally occupied by one or more R 5a A substituted 4- to 12-membered heterocyclic group, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 5. In some embodiments, ring 1 is... Ring 5 is optionally occupied by one or more R 5aSubstituted 4- to 12-membered heterocyclic groups, wherein ring 5 contains at least one N atom, and V is -C(O)- and is attached to a cyclic nitrogen atom of ring 5.

[0120] In some implementations, Q is ring 5, and rings 1, V, and 5 together form a ring. , , , , , , or In some implementations, ring 4 is present.

[0121] In some embodiments of compounds of formula (I) or (II), ring 1 is a 4- to 8-membered heterocyclic ring comprising at least one cyclic ether and not comprising a cyclic amine or cyclic amide, optionally surrounded by one or more R 1 Instead, ring 5 is optionally replaced by one or more R 5a Substituted 4- to 12-membered heterocyclic groups, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 5, and wherein each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl groups; and each R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R)z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or an oxo group. In some embodiments, ring 1 is a 5- to 8-membered heterocyclic ring that does not contain a cyclic amine or cyclic amide, optionally surrounded by one or more R groups. 1 Instead, ring 5 is optionally replaced by one or more R 5a The substituted 4- to 12-membered heterocyclic group, wherein ring 5 comprises at least one N atom, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 5. In some embodiments, ring 1 is a 6- to 8-membered heterocyclic ring that does not contain a cyclic amine or cyclic amide, optionally separated by one or more R... 1 Instead, ring 5 is optionally replaced by one or more R 5a Substituted 4- to 12-membered heterocyclic groups, wherein ring 5 contains at least one N atom, and V is -C(O)- and is attached to a cyclic nitrogen atom of ring 5.

[0122] In some implementations, ring 1 is not R 1 Replacement. In some implementations, ring 1 is replaced by one or more R... 1 Replacement. In some implementations, ring 1 is replaced by 1, 2, or 3 R... 1 Replacement. In some implementations, each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y(R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl group. In some embodiments, each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl or N(R) y )C(O)C 1-4 Halogenated groups. In some embodiments, each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy or CN.

[0123] In some embodiments of the compound of formula (I) or formula (II), the compound has formula (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), or (II-g):

[0124] Or its stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein ring 5 is optionally surrounded by one or more R 5a The 4- to 12-membered heterocyclic groups are replaced, and R, ring 3, and ring 4 are as defined with respect to formula (I). In some such embodiments, ring 5 is optionally replaced by one or more R groups. 5a The substituted 5- to 6-membered heterocyclic group. In some such embodiments, ring 5 is piperidinyl or piperazine, each optionally replaced by one or more R groups. 5a Replacement. In some implementations, ring 4 is present.

[0125] In some embodiments of formula (I) or formula (II) or any applicable related formula, when ring 5 is present, ring 5, ring V and ring 1 together form a group of formula (A'), (B'), (C'), (D'), (E'), (F'), (G'), (H') or (J'):

[0126] In some embodiments of compounds of formula (I) or formula (III) or any applicable related formula, R Q V and ring 1 together form groups of the formula (K'), (L'), (M'), (N'), or (O'):

[0127] In some embodiments of the compound of formula (I), Q has formula (i), (i), And the compound has formula (IV), (IV), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein rings A, X, B, W, C, linker, U, 2, V, 1, R, 3, and 4 are detailed herein with respect to formula (I). In some embodiments, ring 4 is present. In some embodiments, ring 2 is present. In some embodiments, rings 2 and 4 are each present. In some embodiments, ring C is present. In some embodiments, rings 2, 4, and C are each present.

[0128] In some embodiments of the compound of formula (I), Q has formula (i), (i), And the compound has formula (IV), (IV), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R...3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C(O)O-#, -OC(O)# -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-OC(O)N(R V )-#、-N(R V -C(O)O#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Ring A can be selected from the following groups: , , and Each of them is optionally controlled by one or more Cs 1-4 Alkyl or halogenated groups; X is a bond, -O-, -NH-, or -NHC(O)-; Ring B can be selected from the following groups: , , , , , and Each of them is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4 Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a bond, -O-, -NH-, or -NHC(O)-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. C Substituted 4- to 12-membered heterocyclic groups; The connectors are key, -O-, C 1-10 Alkylene, C 1-10Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**,in *Indicates the connection point with ring C when ring C exists, and *Indicates the connection point with W when ring C does not exist; and **Indicates the connection point with U when ring 2 exists, and** indicates the connection point with V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ); When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a bond or C(O); Ring 2 is optional, and when present, is selected from the following groups: optionally by one or more R... 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The 6 to 12 aryl groups are replaced, and optionally by one or more R groups. 2b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a and R 4a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b and R 4b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C 1-4 Hydroxyalkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R w Independently a 3- to 10-membered cycloalkyl group, optionally substituted with a halogen group, or optionally substituted with a hydroxyl group, C 1-4 Hydroxyalkyl or C 1-4Aminoalkyl-substituted 4- to 12-membered heterocyclic groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl, 3- to 10-membered cycloalkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic lactam, or (b) V contains amides or carbamates, or (c) V together with the atoms of the ring 1 or ring 2 to which it is attached forms an amide or carbamate; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group.

[0129] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring A is selected from the group consisting of: , , and Each of them is arbitrarily assigned by C 1-4 Alkyl or halogenated groups are used for substitution. In some embodiments, ring A is optionally replaced by C. 1-4 Alkyl or halogen-substituted In some implementations, ring A is... .

[0130] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), X is a bond, -O-, -NH-, or -NHC(O)-. In some embodiments, X is a bond or -NH-.

[0131] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring B is selected from the group consisting of: , , , , , and Each of them is optionally replaced by one or more halogen groups or OH groups, wherein R D For H or C 1-4 Alkyl group. In some embodiments, ring B is selected from the group consisting of: , , , , , and Each of them is optionally replaced by one or more halogen groups or OH groups, wherein R D For H or C 1-4 Alkyl group, # indicates connection to X, and ## indicates connection to W. In some embodiments, ring B is optionally substituted with one or more halogen groups or OH groups. or In some implementations, ring B is... or .

[0132] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), W is a bond, -O-, -NH-, or -NHC(O)-. In some embodiments, W is a bond or -O-.

[0133] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), the ring C is absent.

[0134] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-c), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring C is present and optionally surrounded by one or more R C Substituted 4- to 12-membered heterocyclic groups, wherein each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups. In some embodiments, the ring C is optionally separated by one or more R groups. C Substituted 4- to 12-membered nitrogen-containing heterocyclic groups. In some embodiments, the ring C is optionally replaced by one or more R groups. C The 5- to 6-membered heterocyclic group is replaced. In some embodiments, ring C is optionally replaced by one or more R groups. C Replacement Where Y and Z are independently CH or N. In some embodiments, ring C is piperidinyl or piperazineyl, each optionally surrounded by one or more R C Replacement. In some implementations, ring C is optionally replaced by one or more R C Substituted piperidinyl group. In some embodiments, the ring C is optionally replaced by one or more R groups. C Substituted piperazine group. In some embodiments, the ring C is... , or Each of them is optionally controlled by one or more R C Replacement. In some implementations, ring C is... , or Each of them is optionally controlled by one or more R C Instead, where # indicates connection to W and ## indicates connection to the connector. In some embodiments, ring C is... , or , where # indicates connection to W and ## indicates connection to the connector.

[0135] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), the linker is a bond, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**, where * indicates connection to ring C when ring C exists, or connection to W when ring C does not exist, and ** indicates connection to U when ring 2 exists, or connection to V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups, wherein each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated alkyl groups; and L 3 C 1-10Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ).

[0136] In some embodiments of compounds of formula (I'), (I), or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), the linker is a bond, -O-, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L1 -L 2 -L 3 -**, where * indicates connection to ring C when ring C exists, or connection to W when ring C does not exist, and ** indicates connection to U when ring 2 exists, or connection to V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups, wherein each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated alkyl groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ).

[0137] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), the linker is a bond, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y In some embodiments of compounds of formula (I) or (IV), the linker is a bond, C 1-10 Alkylene or C(O)C 1-10 Alkylene.

[0138] In some embodiments of compounds of formula (I) or (IV), the linker is a bond, C 1-10 Alkylene, C(O)-C 1-10 Alkylene, C 1-6 Alkylene-C(O)-C 1-10 Alkylene, C 0-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene or having the formula *-L 1 -L 2 -L 3 -**, where L 1 For key or C 1-6 Alkylene, L 2 It is a piperidinyl ring or a piperazine ring, and L 3 C 1-10 Alkylene. In some embodiments, the connector is a bond, C 1-2 Alkylene, C(O)-C 1-2 Alkylene or C 1-2 Alkylene-C(O)N(R) y )-C 1-10 Alkylene.

[0139] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-c), or (IV-d), ring 2 is absent.

[0140] In some embodiments of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 2 is selected from the group consisting of: optionally being one or more R 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The substituted 6 to 12 aryl groups and optionally one or more R 2b Substituted 5 to 12 heteroaryl groups, wherein each R 2a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxo groups; and each R 2b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R)z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x And U is the key. In some implementations, it is optionally controlled by one or more R... 2a The substituted 4- to 12-membered heterocyclic groups are nitrogen-containing heterocyclic groups.

[0141] In some embodiments of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 2 is selected from the group consisting of: optionally being one or more R 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The substituted 6 to 12 aryl groups and optionally one or more R 2b Substituted 5 to 12 heteroaryl groups, wherein each R 2a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y)C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxo groups; and each R 2b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x And U is C(O). In some implementations, it is optionally controlled by one or more R 2a The substituted 4- to 12-membered heterocyclic groups are nitrogen-containing heterocyclic groups.

[0142] In some embodiments of equation (I) or (IV) or any related equation such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 2 is optionally bounded by one or more R 5a Replacement C 3-10 cycloalkyl, wherein each R 2a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or an oxy group. In some embodiments, ring 2 is optionally surrounded by one or more R groups. 5a Replacement C 5-10 Cycloalkyl. In some embodiments, ring 2 is optionally surrounded by one or more R... 5a Replacement C 5-6 Cycloalkyl. In some embodiments, ring 2 is optionally surrounded by one or more R... 5a Substituted C6 cycloalkyl groups.

[0143] In some implementation schemes, ring 2 is , or Each of them is optionally controlled by one or more R2a Replace, where # indicates that it is connected to V.

[0144] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 2 is optionally surrounded by one or more R 2a Substituted 4- to 12-membered heterocyclic groups, wherein each R 2a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or an oxy group. In some embodiments, ring 2 is optionally surrounded by one or more R groups. 2a The 5- to 6-membered heterocyclic group is replaced. In some embodiments, ring 2 is optionally replaced by one or more R groups. 2a Substituted 4- to 12-membered nitrogen-containing heterocyclic groups. In some embodiments, ring 2 is optionally replaced by one or more R groups. 2a The substituted 5- to 6-membered nitrogen-containing heterocyclic group. In some embodiments, ring 2 is piperidinyl or piperazine, each optionally replaced by one or more R groups. 2aReplacement. In some implementations, ring 2 is optionally replaced by one or more R 2a The 10- to 12-membered heterocyclic group is replaced. In some embodiments, ring 2 is... , , or Each of them is optionally controlled by one or more R 2a Instead, where # indicates a connection to V. In some implementations, ring 2 is... , or Each of them is optionally controlled by one or more R 2a Instead, where # indicates a connection to V. In some implementations, ring 2 is... In some implementations, ring 2 is... In some implementations, ring 2 is... In some implementations, ring 2 is... .

[0145] In some embodiments of compounds of formula (I) or (IV) or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 2 is optionally surrounded by one or more R 5b Substituted 5 to 12 heteroaryl groups, wherein each R 2b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x In some implementations, ring 2 is optionally bounded by one or more R... 5b Substituted 5- to 6-membered heteroaryl groups.

[0146] In some embodiments of compounds of formula (I') or any related formula such as (I), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (IV-a), (IV-a), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n Rx Or an oxy group. In some embodiments, each R 2a R 3a R 4a and R 5a For C(O)R w In some implementations, each R 3a For C(O)R w .

[0147] In some embodiments of compounds of formula (I') or any related formula such as (I), (IV), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (IV-a), (IV-a), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C 1-4 Hydroxyalkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n Rx In some implementations, each R 2b R 3b R 4b and R 5b Independently for C(O)R w Or C 1-4 Hydroxyalkyl. In some embodiments, each R 2b R 3b R 4b and R 5b Independently for C(O)R w In some implementations, each R 2b R 3b R 4b and R 5b Independently for C 1-4 Hydroxyalkyl. In some embodiments, each R 3b Independently for C(O)R w Or C 1-4 Hydroxyalkyl. In some embodiments, each R 3b Independently for C(O)R w In some implementations, each R 3b Independently for C 1-4 Hydroxyalkyl. In some embodiments, each R 3b for .

[0148] In some implementations, each R w Independently a 3- to 10-membered cycloalkyl group, optionally substituted with a halogen group, or optionally substituted with a hydroxyl group, C 1-4 Hydroxyalkyl or C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups. In some embodiments, each R w Independently, each R is a 3- to 10-membered cycloalkyl group. In some embodiments, each R w Independently, it is a phenyl group optionally substituted with a halogen group. In some embodiments, each R w Optionally substituted with fluorine or chlorine. In some embodiments, each R w Optionally fluorinated phenyl groups. In some embodiments, each R w Optionally substituted phenyl groups. In some embodiments, each R w Independently, optionally by hydroxyl, C 1-4 Hydroxyalkyl or C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups. In some embodiments, each R w These are 4- to 12-membered heterocyclic groups optionally substituted with hydroxyl groups. In some embodiments, each R... w For optional use by C1-4 Hydroxyl-substituted 4- to 12-membered heterocyclic groups. In some embodiments, each R w For optional use by C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups. In some embodiments, R w for , , , , , or .

[0149] In some implementations, each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl, 3- to 10-membered cycloalkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl group. In some embodiments, each R y and R z Independently, it is a 3- to 10-membered cycloalkyl group. In some embodiments, R y and R z One of them is hydrogen and the other is a 3- to 10-membered cycloalkyl group. In some embodiments, R y and R z One of them is hydrogen and the other is cyclopropyl.

[0150] In some implementations, each R V Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups. In some embodiments, each R V Independently H or C 1-4 Alkyl group. In some embodiments, each R V Independently H or C 1-2 Alkyl group. In some embodiments, each R V Independently, it is either H or methyl. In some embodiments, each R V Independently H or ethyl. In some embodiments, each R V For H. In some implementations, each R VFor methyl. In some embodiments, each R V It is an ethyl group.

[0151] In some embodiments of formula (IV), ring C, U, and ring 2 are present, and the compound has formula (IV-a). In some embodiments of formula (IV), U and ring 2 are present, and ring C is absent, and the compound has formula (IV-a). In some embodiments, ring C is present, and U and ring 2 are absent, and the compound has formula (IV-c). In some embodiments, ring C, U, and ring 2 are absent, and the compound has formula (IV-d). In some embodiments, the compound of formula (I) or (IV) has formula (IV-a), (IV-a), (IV-c), or (IV-d):

[0152] Rings A, X, B, W, C, connector, U, 2, V, 1, R, 3, and 4 are as described in this paper with respect to equation (I).

[0153] In some embodiments of formula (I), formula (IV), or any related formula such as (IV-a), (IV-a), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), when ring 2 is present, ring 2, V, and ring 1 together form a group of formula (A), (B), (C), (D), (E), (F), (G), (H), or (J):

[0154] In some such embodiments, ring 2, V, and ring 1 together form a group of formula (C), (D), or (E). In some such embodiments, when ring 2 is present, ring 2, V, and ring 1 together form a group of formula (K), (L), (M), or (N).

[0155] In some such embodiments, when ring 2 is present, ring 2, V, and ring 1 together form a group of formula (O), (P), (Q), or (R) or a stereoisomer thereof:

[0156] In some embodiments of compounds of formula (I), (II), (III), (IV), or any related formula such as (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 1 is a saturated 4- to 8-membered heterocyclic group comprising a cyclic amide, optionally surrounded by one or more R1 Replacement, and V is a bond or C 1-4 Alkylene. In some embodiments, ring 1 is a saturated 5- to 6-membered heterocyclic group comprising a cyclic amide, optionally surrounded by one or more R... 1 Replacement, and V is a bond or C 1-4 Alkylene. In some embodiments, ring 1 is... Optionally by one or more R 1 Replacement, where # indicates connection to V, which is a key or C. 1-4 Alkylene. In some embodiments, ring 1 is... or Each of them is optionally controlled by one or more R 1 Replacement, and V is a bond or C 1-4 Alkylene. In some embodiments, ring 1 is... And V is a key or C 1-4 Alkylene. In some embodiments, ring 1 is... And V is a key or C 1-4 Alkylene.

[0157] In some embodiments of compounds of formula (I), (II), (III), (IV), or any related formula such as (IV-a), (IV-a), (IV-c), or (IV-d), ring 1 is a saturated 4- to 8-membered heterocyclic group comprising at least one cyclic amine, optionally surrounded by one or more R 1 Substitution, and V is -C(O)- or -C 1-4 Alkylene-C(O)-. In some embodiments of compounds of formula (I), ring 1 is a saturated 5- to 8-membered heterocyclic group comprising at least one cyclic amine, optionally separated by one or more R... 1 Substitution, and V is -C(O)- or -C 1-4 Alkylene-C(O)-. In some embodiments of compounds of formula (I), ring 1 is a saturated 6- to 8-membered heterocyclic group comprising at least one cyclic amine, optionally separated by one or more R... 1 Substitution, and V is -C(O)- or -C 1-4 Alkylene-C(O)-. In some embodiments, ring 1 is piperidinyl or 2-azaspiro[3.3]heptyl, each optionally separated by one or more R 1 Substitution, and V is -C(O)- or -C 1-4 Alkylene-C(O)-. In some embodiments, ring 1 is... or The # symbol is connected to V, each of which is optionally linked to one or more R symbols. 1 Substitution, and V is -C(O)- or -C 1-4 Alkylene-C(O)-. In some embodiments, ring 1 is... , or The # symbol is connected to V, each of which is optionally linked to one or more R symbols. 1 Substitution, and V is -C(O)- or -C 1-4 Alkylene-C(O)-. In some embodiments, ring 1 is... And V is -C(O)- or -C 1-4 Alkylene-C(O)-. In some embodiments, ring 1 is... And V is -C(O)- or -C 1-4 Alkylene-C(O)-. In some embodiments, ring 1 is... And V is -C(O)- or -C 1-4 Alkylene-C(O)-.

[0158] In some embodiments of compounds of formula (I), (II), (III), (IV), or any related formula such as (IV-a), (IV-a), (IV-c), or (IV-d), ring 1 is optionally surrounded by one or more R 1 Replacement C 4-8 Cycloalkyl, and V is -C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#.

[0159] In some embodiments of compounds of formula (I), (IV), or any related formula such as (IV-a) or (IV-a), ring 1 is optionally surrounded by one or more R 1 Replacement C 4-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R 2a The substituted 4 to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2. In some embodiments, ring 1 is optionally separated by one or more R 1 Replacement C 5-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R 2a The substituted 4 to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2. In some embodiments, ring 1 is optionally separated by one or more R 1 Replacement C 6-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R 2aThe substituted 4 to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 2. In some embodiments, ring 1 is cyclohexyl or spiroheptyl, each optionally substituted with one or more R 1 Replacement, ring 2 is optionally replaced by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... or Each of them is optionally controlled by one or more R 1 Replacement, ring 2 is optionally replaced by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... , or Each of them is optionally controlled by one or more R 1 Replacement, ring 2 is optionally replaced by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... Ring 2 is optionally bounded by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... Ring 2 is optionally bounded by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... Ring 2 is optionally bounded by one or more R 2a The substituted 4 to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2.

[0160] In some embodiments of compounds of formula (I), (IV), or any related formula such as (IV-a) or (IV-a), ring 1 is optionally surrounded by one or more R 1 Replacement C 4-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R 2a The substituted 4 to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2. In some embodiments, ring 1 is optionally separated by one or more R 1 Replacement C 5-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R 2aThe substituted 4 to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2. In some embodiments, ring 1 is optionally separated by one or more R 1 Replacement C 6-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R 2a The substituted 4 to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom of ring 2. In some embodiments, ring 1 is cyclohexyl or spiroheptyl, each optionally substituted with one or more R 1 Replacement, ring 2 is optionally replaced by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... , , or Each of them is optionally controlled by one or more R 1 Replacement, ring 2 is optionally replaced by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... , , , or Each of them is optionally controlled by one or more R 1 Replacement, ring 2 is optionally replaced by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... Ring 2 is optionally bounded by one or more R 2a The substituted 4- to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to a cyclic nitrogen atom in ring 2. In some embodiments, ring 1 is... Ring 2 is optionally bounded by one or more R 2a The substituted 4 to 12-membered nitrogen-containing heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2. In some embodiments, ring 1 is optionally separated by one or more R 1 Replacement C 4-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R 2a Replacement C 4-8 Cycloalkyl, and V is -C(O)N(R) V )-#, where # indicates the connection point with ring 1. In some embodiments, ring 1 is optionally connected by one or more R 1 Replacement C 5-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R2a Replacement C 5-8 Cycloalkyl, and V is -C(O)N(R) V )-#, where # indicates the connection point with ring 1. In some embodiments, ring 1 is optionally connected by one or more R 1 Replacement C 6-8 Cycloalkyl, ring 2 is optionally surrounded by one or more R 2a Replacement C 6-8 Cycloalkyl, and V is -C(O)N(R) V )-#, where # indicates the connection point with ring 1. In some embodiments, ring 1 is optionally connected by one or more R 1 The substituted cyclohexyl group, ring 2 is optionally replaced by one or more R groups. 2a Substituted cyclohexyl group, and V is -C(O)N(R) V )-#, where # indicates the connection point with ring 1.

[0161] In some embodiments of compounds of formula (I) or (IV), ring 2 is present and the compound has formula (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l):

[0162] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 3 is optionally surrounded by one or more R 3a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 3a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 3b Substituted phenyl, or optionally with one or more R 3b Substituted 5 to 6 heteroaryl groups, wherein each R 3a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group, and each R 3b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x In some implementations, each R 3a Independently, it is a halogenated group, methyl group, trifluoromethyl group, OH group, OCH3 group, acetyl group, CN group, or oxo group. In some embodiments, each R group... 3a It is an oxygen group. In some embodiments, each R 3bIt can be a halogen, methyl, trifluoromethyl, OH, OCH3, acetyl or CN group independently.

[0163] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 3 is optionally surrounded by one or more R 3a Substituted 3- to 6-membered cycloalkyl groups.

[0164] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 3 is optionally surrounded by one or more R 3a Substituted 4- to 6-membered heterocyclic groups. In some embodiments of compounds of formula (I), ring 3 is optionally replaced by one or more R groups. 3a The substituted 4- to 6-membered nitrogen-containing heterocyclic group. In some embodiments, ring 3 is pyrrolidinyl, piperidinyl, piperazineyl, or morpholinyl. In some embodiments, ring 3 is... , , or Each of them is optionally controlled by one or more R 3a Replacement. In some implementations, ring 3 is... , , , , , , or Each of them is optionally controlled by one or more R 3a Replacement, where # indicates connection to the pyrimidine ring of formula (I), and ## indicates connection to ring 4 (if present). In some embodiments, ring 3 is , , Each of them is optionally controlled by one or more R 3a Replacement. In some implementations, ring 3 is... , , , or , where # indicates connection to the pyrimidine ring of formula (I), and ## indicates connection to ring 4 (if present).

[0165] In some embodiments of compounds of formula (I), (II), (III) or (IV), or related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 3 is optionally surrounded by one or more R 3b Substituted phenyl groups. In some embodiments, ring 3 is optionally replaced by one or more R groups. 3b Replacement In some implementations, ring 3 is... In some implementations, ring 3 is... , or In some implementations, each R 3b Independently, it can be a halogen, methyl, trifluoromethyl, OH, OCH3, acetyl, or CN. In some embodiments, each R... 3b It can be a halogen, methyl, or OCH3 group independently.

[0166] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 3 is optionally surrounded by one or more R 3b The 5- to 6-membered heteroaryl group is replaced. In some embodiments, ring 3 is optionally replaced by one or more R groups. 3b The substituted 5- to 6-membered nitrogen-containing heteroaryl group. In some embodiments, ring 3 is optionally replaced by one or more R 3b The substituted 6-membered heteroaryl group. In some embodiments, ring 3 is optionally replaced by one or more R... 3b The substituted 5-membered heteroaryl group. In some embodiments, ring 3 is optionally replaced by one or more R 3b The substituted pyrazol group. In some embodiments, ring 3 is... , or Each of them is optionally controlled by one or more R 3b Replacement. In some implementations, ring 3 is... , , , or Each of them is optionally controlled by one or more R 3b Replacement, where # indicates connection to the pyrimidine ring of formula (I), and ## indicates connection to ring 4 (if present). In some embodiments, ring 3 is or , where # indicates connection to the pyrimidine ring of formula (I), and ## indicates connection to ring 4 (if present). In some embodiments, ring 3 is optionally connected to one or more R 3b The substituted 6-membered heteroaryl group. In some embodiments, ring 3 is optionally replaced by one or more R... 3b Substituted pyridinyl, pyrimidinyl, or pyrazinyl groups.

[0167] In some implementation schemes, ring 3 is or Each of them is optionally controlled by one or more R3b Substitution, where # indicates connection to the pyrimidine ring of formula (I), and ## indicates connection to ring 4 (if present).

[0168] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 3 is not a 5-membered heteroaryl group, and ring 4 is absent. In some such embodiments, ring 3 is optionally separated by one or more R 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b The substituted 6-membered heteroaryl group is present, and ring 4 is absent. In some such embodiments, ring 3 is optionally replaced by one or more R groups. 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; or optionally, replaced by one or more R groups. 3b The substituted phenyl group; and ring 4 is absent.

[0169] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 4 is present. In some embodiments, ring 4 is present and is not substituted. In some embodiments, ring 4 is present and is not substituted or is substituted with a halogen group. In some embodiments, ring 4 is a phenyl group substituted with a halogen group. In some embodiments, ring 4 is a phenyl group substituted with a fluorine group.

[0170] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 4 is present and is a monocyclic ring selected from the group consisting of: optionally surrounded by one or more R 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5 to 6 heteroaryl groups, wherein each R 4a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R)y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group, and each R 4b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x Where ring 3 is a 5-membered heteroaryl group, ring 4 is not a cycloalkyl or tetrahydropyranyl group. In some embodiments, each R 4a Independently, it is a halogenated group, methyl group, trifluoromethyl group, OH group, OCH3 group, acetyl group, CN group, or oxo group. In some embodiments, each R group... 4a It is methyl or acetyl. In some embodiments, each R 4b It can be a halogen, methyl, trifluoromethyl, OH, OCH3, acetyl or CN group independently.

[0171] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 4 is optionally surrounded by one or more R 4a The substituted 3- to 6-membered cycloalkyl group and ring 3 is not a 5-membered heteroaryl group. In some embodiments, ring 4 is optionally replaced by one or more R groups. 4a The substituted 4- to 6-membered cycloalkyl group, and ring 3 is not a 5-membered heteroaryl group. In some embodiments, ring 4 is optionally replaced by one or more R groups. 4a The substituted cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group is used, and ring 3 is not a 5-membered heteroaryl group. In some embodiments, ring 4 is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and ring 3 is not a 5-membered heteroaryl group. In some embodiments, ring 4 is cyclobutyl, cyclopentyl, or cyclohexyl, and ring 3 is not a 5-membered heteroaryl group.

[0172] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 4 is optionally surrounded by one or more R 4a The substituted 4- to 6-membered heterocyclic group, wherein when ring 3 is a 5-membered heteroaryl group, ring 4 is not a tetrahydropyranyl group. In some embodiments, ring 4 is optionally replaced by one or more R groups. 4aSubstituted 4- to 6-membered nitrogen-containing heterocyclic groups. In some embodiments, ring 4 is optionally replaced by one or more R groups. 4a The substituted 5- to 6-membered nitrogen-containing heterocyclic group. In some embodiments, ring 4 is pyrrolidinyl, piperidinyl, or piperazineyl, each optionally replaced by one or more R groups. 4a Substitution. In some embodiments, ring 4 is pyrrolidinyl or piperidinyl, each optionally replaced by one or more R... 4a Replacement. In some implementations, ring 4 is... , , , or Each of them is optionally controlled by one or more R 4a Replacement. In some implementations, ring 4 is... , , , , , or In some implementations, each R 4a Independently, it is a halogenated group, methyl group, trifluoromethyl group, OH group, OCH3 group, acetyl group, CN group, or oxo group. In some embodiments, each R group... 4a It can be methyl or acetyl.

[0173] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 4 is optionally surrounded by one or more R 4b Substituted phenyl groups. In some embodiments, ring 4 is... , , or In some implementations, each R 4a Independently, it can be a halogen, methyl, trifluoromethyl, OH, OCH3, acetyl, or CN. In some embodiments, each R... 4a It can be a halogen, methyl, or OCH3.

[0174] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 4 is optionally surrounded by one or more R 4b The 5- to 6-membered heteroaryl group is replaced. In some embodiments, ring 4 is optionally replaced by one or more R groups. 4b The substituted 5- to 6-membered nitrogen-containing heteroaryl group. In some embodiments, ring 4 is optionally replaced by one or more R... 4b A substituted 6-membered heteroaryl group. In some embodiments, ring 4 is pyridyl or pyrazinyl, each optionally replaced by one or more R groups. 4b Replacement. In some implementations, ring 4 is... , , or Each of them is optionally controlled by one or more R 4b Replacement. In some implementations, ring 4 is... , or Each of them is optionally controlled by one or more R 4b Replacement. In some implementations, ring 4 is... , or .

[0175] In some implementations, ring 4 is optionally bounded by one or more R 4b Replacement .

[0176] In some implementation schemes, ring 4 is... , , , , , , , , or Each of them is optionally controlled by one or more R 4a replace.

[0177] In some implementation schemes, ring 4 is... , or Each of them is optionally controlled by one or more R 4a replace.

[0178] In some embodiments of compounds of formulas (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 3 is optionally surrounded by one or more R 3a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 3a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 3b Substituted phenyl, or optionally with one or more R 3b The substituted 6-membered heteroaryl group; and ring 4 is absent. In some embodiments of the compound of formula (I), ring 3 is optionally replaced by one or more R groups. 3a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 3a The substituted 4- to 6-membered heterocyclic group, or optionally replaced by one or more R groups. 3b The substituted phenyl group; and ring 4 is absent.

[0179] In some embodiments of compounds of formula (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), ring 3 is a 5-membered heteroaryl group, and ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group. In some embodiments of the compound of formula (I), ring 3 is a 5-membered heteroaryl group, and ring 4 is present and optionally surrounded by one or more R groups. 4a The substituted 4 to 6-membered nitrogen-containing heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl, or optionally with one or more R 4b Substituted 5- to 6-membered heteroaryl groups. In some embodiments of compounds of formula (I), ring 3 is a 5-membered heteroaryl group, and ring 4 is present and optionally substituted with one or more R groups. 4b Substituted phenyl, or optionally with one or more R 4b Substituted 5- to 6-membered heteroaryl groups.

[0180] In some embodiments, ring 3 is phenyl, and ring 4 is present and optionally surrounded by one or more R 4a The substituted 4 to 6-membered nitrogen-containing heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl, or optionally with one or more R 4b Substituted 5- to 6-membered heteroaryl groups. In some embodiments, ring 3 is phenyl and ring 4 is present and optionally replaced by one or more R groups. 4a Substituted 4- to 6-membered nitrogen-containing heterocyclic groups. In some embodiments, ring 3 is phenyl and ring 4 is present and is... .

[0181] In some embodiments of compounds of formula (I), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), ring 4 is absent and Q has formula (i). In some embodiments, ring 4 is present and Q has formula (i).

[0182] In some implementations, ring 4 is absent. In some implementations, ring 4 is present.

[0183] In some embodiments of compounds of formula (I), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (IV-a), (IV-a), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), rings A, X, B, W, and C together form: , , , , , , , , , , or Each of them Optionally by one or more R C Replacement, where Y and Z are independently CH or N. In some embodiments, rings A, X, B, W, and C together are: , , , or Each of them Optionally by one or more R C Replacement, where Y and Z are independently CH or N. In some embodiments, rings A, X, B, W, and C together are: , or Each of them Optionally by one or more R C Replacement, where Y and Z are independently CH or N. In some embodiments, rings A, X, B, W, and C together are: Each of them Optionally by one or more R C Replace, where Y and Z are independently CH or N.

[0184] In some implementations, rings A, X, B, W, and C together form: ,in Optionally R 2b Replace, each of them Optionally by one or more R C Replace, where Y and Z are independently CH or N.

[0185] In some embodiments, when ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group; and when ring 1 is an 8-membered heterocyclic group, ring 3 is a CN-substituted phenyl group, ring 4 is absent, and Q is R. Q And when V is -OC(O)#, then R Q Not tert-butyl. In some embodiments, when ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group. In some embodiments, when ring 1 is an 8-membered heterocyclic group, ring 3 is a CN-substituted phenyl group, ring 4 is absent, and Q is R. Q And when V is -OC(O)#, then R Q Not schuding.

[0186] It should be understood that all embodiments of equation (I) and its sub-equations also apply to equations (II), (III), and (IV), including all sub-equations and their variations (where applicable). Furthermore, this disclosure covers combinations of features as disclosed herein, as if each were listed separately. Exemplary combinations of features are provided herein but should not be construed as limiting.

[0187] It should be understood that all embodiments of equation (I) and its sub-equations also apply to equations (I'), (II), (III), and (IV), including all sub-equations and their variations (where applicable). Furthermore, this disclosure covers combinations of features as disclosed herein, as if each were listed separately. Exemplary combinations of features are provided herein but should not be construed as limiting.

[0188] Representative compounds are listed in Tables 1 and 2.

[0189] In some embodiments of compounds of formula (I') or (I), or any variations or embodiments thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, are selected from Table 1 or Table 2. In some embodiments of compounds of formula (I') or (I), or any variations or embodiments thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, are selected from Table 1. In some embodiments of compounds of formula (I') or (I), or any variations or embodiments thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, are selected from Table 2.

[0190] In some embodiments of a compound of formula (I') or (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or any stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from compounds 1-43 and 91 of Table 1, and compounds 44-90 of Table 2. In some embodiments of a compound of formula (I') or (I), or any variation thereof or embodiment thereof, or any stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, the compound, or any stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from compounds 1-43 and 91-274 of Table 1, and compounds 44-90 and 275-605 of Table 2. In some embodiments of compounds of formula (I') or (I), or any variations or embodiments thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, are selected from compounds 1-43, 91-274, and 606-631 of Table 1, and compounds 44-90, 275-605, and 632-705 of Table 2. In some embodiments of compounds of formula (I') or (I), or any variations or embodiments thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, are selected from compounds 1-43 and 91 of Table 1. In some embodiments of compounds of formula (I') or (I), or any variation or embodiment thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, is selected from compounds 1-43 and 91-274 of Table 1. In some embodiments of compounds of formula (I') or (I), or any variation or embodiment thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, is selected from compounds 1-43, 91-274, and 606-631 of Table 1. In some embodiments of compounds of formula (I') or (I), or any variation or embodiment thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts thereof, the compounds, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts thereof, are selected from compounds 44-90 of Table 2.In some embodiments of compounds of formula (I') or (I), or any variation or embodiment thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, is selected from compounds 44-90 and 275-605 of Table 2. In some embodiments of compounds of formula (I') or (I), or any variation or embodiment thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, the compound, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, is selected from compounds 44-90, 275-605, and 632-705 of Table 2.

[0191] Table 1: Representative compounds of formula (I'), formula (I), formula (II) and formula (III)

[0192] Table 2: Representative compounds of formula (I'), formula (I) and formula (IV)

[0193] Pharmaceutical Composition Another aspect of the present invention relates to a pharmaceutical composition comprising formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac). Compounds of (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers. In some embodiments, the pharmaceutical composition comprises a therapeutically effective amount of formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I- Compounds of (ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and one or more pharmaceutically acceptable carriers or excipients. Representative pharmaceutically acceptable carriers and excipients are disclosed, for example, in Remington: The Science and Practice of Pharmacy (20th edition), edited by AR Gennaro, Lippincott Williams & Wilkins, 2000; Encyclopedia of Pharmaceutical TechnologyEdited by J. Swarbrick and J.C. Boylan, 1988–1999, Marcel Dekker, New York; and Handbook of Pharmaceutical Excipients (3rd edition) Edited by AH Kibbe, Amer. Pharm. Assoc., 2000; each of the references is incorporated herein by reference in its entirety.

[0194] Formula (I'), (I), (II), (III), (IV), or any related formula such as formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af Compounds of (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, may be formulated into compositions according to conventional pharmaceutical practice (see, for example, Remington: The Science and Practice of Pharmacy (20th edition), edited by AR Gennaro, Lippincott Williams & Wilkins, 2000 and Encyclopedia of Pharmaceutical Technology (Edited by J. Swarbrick and JC Boylan, 1988–1999, Marcel Dekker, New York, each incorporated herein by reference in its entirety). The type of formulation depends on the mode of administration, which may include, for example, enteric, parenteral, and topical administration.

[0195] In some embodiments, the compound is formulated for oral or intravenous (iv) administration (e.g., systemic intravenous injection). In some embodiments, the compound is formulated for oral administration. In some embodiments, the compound is formulated for intravenous (iv) administration.

[0196] Therefore, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af) Compounds of (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, may be formulated into solid compositions, liquid compositions, semi-solid compositions, or gaseous compositions.

[0197] Solid dosage forms include capsules (such as gelatin capsules or hard-shell capsules), tablets, pills, powders, and granules.

[0198] Liquid dosage forms for oral administration include solutions, suspensions, emulsions, microemulsions, and syrups.

[0199] Injectable formulations intended for parenteral administration may be formulated using dispersions / wetting and suspending agents according to standard techniques. Sterile injectable formulations may be sterile injectable solutions, suspensions, or emulsions in non-toxic, parenteral-acceptable diluents or solvents.

[0200] Formula (I'), (I), (II), (III), (IV), or any related formula such as formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), ( In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-a Compounds of (e), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, may be formulated for administration by inhalation.

[0201] Formula (I'), (I), (II), (III), (IV), or any related formula such as formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), ( Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af) Compounds of (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, may be formulated for topical application, wherein, as used herein, it means intradermal application to the epidermis.

[0202] In some embodiments, the topical formulation may also include excipients, such as penetration enhancers. See, for example... Percutaneous Penetration EnhancersMaibach HI and Smith HE (eds.), CRCPress, Inc., Boca Raton, Fla. (1995), and Buyuktimkin et al. Chemical Means of Transdermal Drug Permeation Enhancement in Transdermal and Topical Drug Delivery Systems , Gosh TK, Pfister WR, Yum SI (ed.), InterpharmPress Inc., Buffalo Grove, Ill. (1997), each incorporated herein by reference in its entirety.

[0203] Dosage The total daily dose of the compound can be determined according to standard medical practice (see, for example...). Goodman and Gilman's The Pharmacological Basis of Therapeutics , 10th edition, edited by A. Gilman, J. Hardman and L. Limbird, McGraw-Hill Press, 155-173, 2001, which is incorporated herein by reference in its entirety.

[0204] How to use In some aspects, a method for treating a disease or condition is provided, the method comprising reducing the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, including administering to a subject in need formula (a), (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), ( Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d) , (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their mutual A variant or stereoisomer, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I- Compounds of (ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some aspects, a method for treating a disease or condition is provided, the method comprising reducing the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, the method comprising administering to a subject in need formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw) Compounds of (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.In some aspects, a method for treating a disease or condition is provided, the method comprising reducing the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, comprising administering to a subject in need a therapeutically effective amount of formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It ), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d ), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their mutual (a) A variant or stereoisomer, or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising a therapeutically effective amount of formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa). Compounds of (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some aspects, a method for treating a disease or condition is provided, the method comprising reducing the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, including administering to a subject in need a therapeutically effective amount of formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw). Compounds of (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing. In some embodiments, the method includes reducing the level or activity of PIP4K2C.

[0205] In some embodiments, compared with untreated control subjects, the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C in the subject is reduced by about 5% to about 100%, for example, by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100%. In some embodiments, at least the level or activity of PIP4K2C is reduced.

[0206] In some embodiments, degradation or depletion of PIP4K2A, PIP4K2B, and / or PIP4K2C proteins (e.g., PIP4K2C protein) treats cancer. In some embodiments, degradation or depletion of PIP4K2A, PIP4K2B, and / or PIP4K2C proteins (e.g., PIP4K2C protein) can be used to diagnose cancer. In some cases, PIP4K2C protein is degraded compared to PIP4K2A and PIP4K2B proteins. In some embodiments, degradation or depletion of PIP4K2A, PIP4K2B, and / or PIP4K2C proteins (e.g., degradation or depletion of PIP4K2C protein) enhances the immune response against cancer and tumors. In some embodiments, depletion or degradation of PIP4K (e.g., degradation or depletion of PIP4K2B protein) treats insulin resistance.

[0207] In some embodiments, the compounds or compositions described herein reduce PIP4K2B levels in patients with or suspected of having insulin resistance. In some embodiments, the compounds or compositions described herein reduce PIP4K2C levels in patients with cancer, immunodeficiency, autoimmune diseases, or infectious diseases, or combinations thereof, or suspected of having cancer, immunodeficiency, autoimmune diseases, or infectious diseases, or combinations thereof.

[0208] In some aspects, a method is provided to enhance the immune function of a subject in need, the method comprising administering to the subject formula (a) (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (I... Compounds of (I-z), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or any of the foregoing. (a) pharmaceutically acceptable salts of the drug, or (b) pharmaceutical compositions comprising formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some aspects, a method is provided to enhance the immune function of a subject in need, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-a) Compounds of (a), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.In some aspects, a method is provided to enhance the immune function of a subject in need, the method comprising administering to the subject a therapeutically effective amount of formula (a), (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy). Compounds of (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or the aforementioned compounds. A pharmaceutically acceptable salt of any of the above, or (b) a pharmaceutical composition comprising formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-a c), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some aspects, a method is provided to enhance the immune function of a subject in need, the method comprising administering to the subject a therapeutically effective amount of formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I... Compounds of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.

[0209] In some implementations, the immune function of the subject is enhanced by about 5% to about 100% compared with untreated control subjects, for example, by at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% compared with untreated control subjects.

[0210] In some aspects, a method for stimulating the immune system is provided, the method comprising reducing, in a subject in need, the scaffolding or interaction of at least one of PIP4K2A, PIP4K2B, and PIP4K2C with at least one of PIP4K2A, PIP4K2B, and PIP4K2C or phosphatidylinositol-4-phosphate 5-kinase (PIP5K), including administering to the subject formula (a), (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik). (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I- af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV- (h), (IV-j), (IV-k), or (IV-l) compounds, or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, or (b) pharmaceutical compositions comprising formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy). Compounds of (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some aspects, a method for stimulating the immune system is provided, the method comprising reducing, in a subject in need, the scaffolding or interaction of at least one of PIP4K2A, PIP4K2B, and PIP4K2C with at least one of PIP4K2A, PIP4K2B, and PIP4K2C or phosphatidylinositol-4-phosphate 5-kinase (PIP5K), including administering to the subject formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (I Compounds of (r), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.In some embodiments, a method for stimulating the immune system is provided, the method comprising reducing, in a subject in need, the scaffolding or interaction of at least one of PIP4K2A, PIP4K2B, and PIP4K2C with at least one of PIP4K2A, PIP4K2B, and PIP4K2C or phosphatidylinositol-4-phosphate 5-kinase (PIP5K), including administering to the subject a therapeutically effective amount of formula (a), (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij) ), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-a e), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g) (IV-h), (IV-j), (IV-k), or (IV-l) compounds, or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, or (b) pharmaceutical compositions comprising formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (I... Compounds of (I-y), (I-z), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, a method for stimulating the immune system is provided, the method comprising reducing, in a subject in need, the scaffolding or interaction of at least one of PIP4K2A, PIP4K2B, and PIP4K2C with at least one of PIP4K2A, PIP4K2B, and PIP4K2C or phosphatidylinositol-4-phosphate 5-kinase (PIP5K), including administering to the subject a therapeutically effective amount of formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (I Compounds of (q), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing. In some implementations, a method for stimulating the immune system is provided, the method comprising reducing the scaffolding or interaction of PIP4K2C with at least one of PIP4K2A, PIP4K2B, or phosphatidylinositol-4-phosphate 5-kinase (PIP5K) in a subject in need. Reduction of scaffolding or interaction can stimulate the immune system.In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I- The vaccine is a component of compounds of (ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or a pharmaceutically acceptable salt thereof. In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I... Compounds of (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, are used as vaccine adjuvants.

[0211] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I- Compounds of (ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing for the treatment of viral infections.In some implementations, a method is provided for treating a viral infection in a subject of need, the method comprising administering to the subject formula (a) (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy). Compounds of (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or the aforementioned compounds. A pharmaceutically acceptable salt of any of the above, or (b) a pharmaceutical composition comprising formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-a c), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some implementations, a method is provided for treating a viral infection in a subject in need, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I... Compounds of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing. In some embodiments, said compound, or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, are administered in combination with a vaccine for viral infection to enhance the immune response.

[0212] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I... Compounds of (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing for the treatment of bacterial infections (e.g., necrotic soft tissue infections).In some embodiments, a method is provided for treating a bacterial infection in a subject of need, the method comprising administering to the subject formula (a) (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy). Compounds of (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or the aforementioned compounds. A pharmaceutically acceptable salt of any of the above, or (b) a pharmaceutical composition comprising formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-a c), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, a method is provided for treating a bacterial infection in a subject in need, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I... Compounds of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing. In some embodiments, the bacterial infection includes necrotic soft tissue infection.

[0213] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af) Compounds of (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the treatment of diseases or conditions associated with at least one of PIP4K2A, PIP4K2B, and PIP4K2C.In some embodiments, a method is provided for treating a subject in need of a disease or condition associated with at least one of PIP4K2A, PIP4K2B, and PIP4K2C, the method comprising administering to the subject formula (a) (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It) , (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II- d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or Its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, or (b) pharmaceutical compositions comprising formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I... Compounds of (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, a method is provided for treating a subject in need of a disease or condition associated with at least one of PIP4K2A, PIP4K2B, and PIP4K2C, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw) Compounds of (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing. In some embodiments, the disease or symptom is associated with PIP4K2C. In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I... Compounds of (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the treatment of diseases or conditions associated with PIP4K2C.

[0214] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad) Compounds of (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the treatment of proliferative diseases or conditions.In some embodiments, a method is provided for treating a subject with a proliferative disease or condition, the method comprising administering to the subject formula (a), (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix) Compounds of (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or A pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I... Compounds of (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, a method is provided for treating a subject with a proliferative disease or condition, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz). Compounds of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.

[0215] Exemplary non-cancerous (e.g., proliferative) diseases or conditions that can be treated with the compounds or compositions of the present invention include inflammatory, autoimmune, neurodegenerative, cardiac, viral, metabolic, and genetic diseases or disorders, as well as chronic and acute kidney diseases or injuries.

[0216] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad) Compounds of (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the treatment of neurodegenerative diseases and conditions.In some embodiments, a method is provided for treating a neurodegenerative disease or condition in a subject of need, the method comprising administering to the subject formula (a), (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix) Compounds of (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or A pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I... Compounds of (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, a method is provided for treating a neurodegenerative disease or condition in a subject of need, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz). Compounds of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.

[0217] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad) Compounds of (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the treatment of autoimmune diseases and conditions.In some embodiments, a method is provided for treating an autoimmune disease or condition in a subject of need, the method comprising administering to the subject formula (a), (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix) Compounds of (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or A pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I... Compounds of (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, a method is provided for treating an autoimmune disease or condition in a subject of need, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz). Compounds of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing. In some embodiments, the disease or symptom is fibrosis.

[0218] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-a Compounds of (d), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the purpose of promoting wound healing.

[0219] In other embodiments, the method relates to treating a subject with cancer. Formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag) Compounds of (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the treatment of cancers (including primary and metastatic tumors), sarcomas, melanomas, and hematologic malignancies such as leukemia, lymphoma, and multiple myeloma.In some embodiments, a method is provided for treating a subject with a tumor, sarcoma, melanoma, or hematologic malignancy, the method comprising administering to the subject formula (a), (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (I... Compounds of (x), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers. or a pharmaceutically acceptable salt of any of the foregoing, or (b) a pharmaceutical composition comprising formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), ( Compounds of (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, a method is provided for treating a subject with cancer, sarcoma, melanoma, or hematologic malignancy, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (I... The subject may be a compound of (I-z), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing. The subject may be an adult or a pediatric subject. The tumor may be vascularized, substantially non-vascularized, or non-vascularized. In some embodiments, the tumor is a solid tumor. In some embodiments, the cancer is acute myeloid leukemia. In some embodiments, the cancer is colorectal cancer. In some embodiments, the cancer is lung cancer.

[0220] In some embodiments, this document provides a method for degrading PIP4K2C using a compound of formula (I') or any related formula, or its tautomers or stereoisomers, or any of the foregoing in a pharmaceutically acceptable salt configuration. In some embodiments, this document provides a method for degrading PIP4K2C using a compound of formula (I') or any related formula, or its tautomers or stereoisomers, or any of the foregoing in a pharmaceutically acceptable salt configuration, wherein Q has formula (i): (i). In some implementations, this document provides a method using formula (I'), (I) or (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I- Compounds of (aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their tautomers or stereoisomers, or a pharmaceutically acceptable salt degradation method of PIP4K2C.

[0221] In some embodiments, this document provides a method for inhibiting PIP4K using a compound of formula (I') or any related formula, or its tautomers or stereoisomers, or any of the foregoing pharmaceutically acceptable salts, wherein Q is R Q Or ring 5. In some implementations, Q is R. Q In some embodiments, Q is ring 5. In some embodiments, this document provides a method for inhibiting PIP4K using compounds of formula (I'), (I), (II) or (III), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), or (II-g).

[0222] Representative examples of cancer include adrenocortical carcinoma, AIDS-related cancers (e.g., Kaposi's lymphoma and AIDS-associated lymphoid tissue lymphoma), appendix cancer, childhood cancers (e.g., childhood cerebellar astrocytoma, childhood cerebral astrocytoma), basal cell carcinoma, skin cancer (non-melanoma), bile duct cancer, extrahepatic bile duct cancer, intrahepatic bile duct cancer, bladder cancer, urethral bladder cancer, brain cancers (e.g., gliomas and glioblastomas such as brainstem gliomas, gestational trophoblastic tumors, cerebellar astrocytomas, cerebral astrocytomas / malignant gliomas, ependymomas, medulloblastomas, supratentorial primitive neuroectodermal tumors, visual pathway and hypothalamic gliomas). ), breast cancer (e.g., triple-negative breast cancer), bronchial adenoma / carcinoid, carcinoid tumor, nervous system cancers (e.g., central nervous system cancers, central nervous system lymphoma), cervical cancer, chronic myeloproliferative disorders, colorectal cancers (e.g., colorectal cancer, colorectal cancer with microsatellite instability (MSI), colorectal cancer with microsatellite stable (MSS), colon cancer, rectal cancer), lymphoid cysts, mycosis fungoides, Sezary syndrome, endometrial cancer, esophageal cancer, extracranial germ cell tumors, gonadal germ cell tumors, extrahepatic bile duct cancer, eye cancer, intraocular melanoma, retinoblastoma, gallbladder cancer, gastrointestinal cancers (e.g., gastric cancer). Cancer, stomach cancer, small bowel cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors (GIST), bile duct cancer, germ cell tumors, ovarian germ cell tumors, head and neck cancer, neuroendocrine tumors, Hodgkin lymphoma, Ann Arbor stage III and IV childhood non-Hodgkin lymphoma, ROS1-positive refractory non-Hodgkin lymphoma, leukemia, lymphoma, multiple myeloma, hypopharyngeal cancer, intraocular melanoma, ocular cancer, islet cell tumors (endocrine pancreas), kidney cancer (e.g., Wilm's tumor, renal cell carcinoma), liver cancer, lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), ALK-positive degenerative large cell lymphoma, ALK-positive advanced malignant solid tumors, Waldenstrom's macroglobulinema, melanoma, intraocular (ocular) melanoma, Merkel cell carcinoma. Cellular carcinoma, mesothelioma, metastatic squamous neck carcinoma with occult primary origin, multiple endocrine neoplasia (MEN), myelodysplastic syndrome, myelodysplastic / myeloproliferative disorders, nasopharyngeal carcinoma, neuroblastoma, oral cancer (e.g., mouth cancer, lip cancer, oral cancer)Cavity cancer), tongue cancer, oropharyngeal cancer, pharyngeal cancer, laryngeal cancer), ovarian cancer (e.g., ovarian epithelial cancer, ovarian germ cell tumors, low-potency ovarian tumors), pancreatic cancer, pancreatic duct adenocarcinoma, islet cell pancreatic cancer, paranasal sinus and nasal cavity cancer, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pineal blastoma, metastatic degenerative thyroid cancer, undifferentiated thyroid cancer, papillary thyroid cancer, pituitary adenoma, plasmacytoma / multiple myeloma, Pleural pulmonary blastoma, prostate cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, uterine cancer (e.g., endometrial cancer, uterine sarcoma, uterine corpus cancer), squamous cell carcinoma (e.g., head and neck squamous cell carcinoma), testicular cancer, thymoma, thymic carcinoma, thyroid cancer, juvenile xanthogranuloma, transitional cell carcinoma of the renal pelvis and ureter and other urinary organs, urethral cancer, gestational trophoblastic tumor, vaginal cancer, vulvar cancer, hepatoblastoma, rhabdomyosarcoma, and Wilms' tumor.

[0223] In some implementations, the cancer is Hodgkin's lymphoma or non-Hodgkin's lymphoma, such as small lymphocytic lymphoma, lymphoplasmacytic lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma, follicular lymphoma, hairy cell leukemia, and plasmacytoma, such as plasmacytoma and multiple myeloma. See also Hematology Reports . 2024; 16(1):164-178.

[0224] In some implementation schemes, the cancer is defined as acute myeloid leukemia.

[0225] Formula (I'), (I), (II), (III), (IV), or any related formula such as formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io) , (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag) Compounds of (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the treatment of sarcomas, including soft tissue and bone cancers, with representative examples including osteosarcoma or osteogenic sarcoma (bone). (e.g., Ewing's sarcoma), chondrosarcoma (cartilage), leiomyosarcoma (smooth muscle), rhabdomyosarcoma (skeletal muscle), mesothelioma or mesothelioma (membranous cavity lining), fibrosarcoma (fibrous tissue), angiosarcoma or angioendothelioma (blood vessel), liposarcoma (adipose tissue), glioma or astrocytoma (neurogenic connective tissue found in the brain), myxosarcoma (primordial embryonic connective tissue), stromal or mixed mesodermal tumors (mixed connective tissue types), and histiocytic sarcoma (immunocarcinoma).In some embodiments, a method for treating a subject with sarcoma in need is provided, the method comprising administering to the subject formula (a) (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag). (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l) compounds, or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, or (b) pharmaceutical compositions comprising formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io). Compounds of (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or tautomers or stereoisomers thereof, or pharmaceutically acceptable salts of any of the foregoing, and pharmaceutically acceptable carriers.In some embodiments, a method of treating a subject with sarcoma in need is provided, the method comprising administering to the subject formula (I'), (I), (II), (III), (IV), or any related formula such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I- Compounds of (aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k) or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.

[0226] In some implementations, methods are provided for treating subjects with proliferative disorders or conditions of the blood system, liver, brain, lungs, colon, pancreas, prostate, ovaries, breast, skin, or endometrium.

[0227] In some implementations, this article provides treatment for patients with phosphatidylinositol phosphatase. FIG4Methods for subjects with loss-of-function mutations related to disease or condition. In some embodiments, the disease or condition is selected from unis-Varón syndrome, Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 4J, polymicrogyria with epilepsy, and pediatric neurodegeneration with decreased myelination. In some embodiments, the disease or condition is Charcot-Marie-Tooth disease. In some embodiments, the disease or condition is Charcot-Marie-Tooth disease type 4J. SeeCao PMID:36691351; PMCID: PMC10411592.

[0228] Formula (I'), (I), (II), (III), (IV), or any related formula such as formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (I n), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae) The compound, or (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or its tautomers or stereoisomers, or a pharmaceutically acceptable salt of any of the foregoing, may be administered to a patient as a monotherapy or via combination therapy. In some embodiments, the compound may be administered to a patient who has received another therapy (e.g., chemotherapy, radioimmunotherapy, surgical therapy, immunotherapy, radiotherapy, or targeted therapy, or any combination thereof).

[0229] The method of the present invention may require administering formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz) to a patient in a single dose or multiple doses (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 10, 15, 20, or more doses). The compound is a compound of (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof. For example, the frequency of administration may range from once daily to once every eight weeks. In some embodiments, the compound is administered approximately once daily. In other embodiments, the compound is administered twice daily (BID).

[0230] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I- The use of compounds of (I-a), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for the manufacture of pharmaceutical agents. In some embodiments, the use is for the manufacture of pharmaceutical agents for diseases or conditions as disclosed herein.

[0231] In some implementations, equations (I'), (I), (II), (III), (IV), or any related equations such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I... The use of compounds of (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, for therapeutic purposes. In some embodiments, the use is for treating a disease or condition as disclosed herein. In some embodiments, the use is for use in methods as disclosed herein.

[0232] In some implementations, formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I- The compounds are (I-ac), (I-ad), (I-ae), (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing. In some embodiments, the compounds are for treating a disease or condition as disclosed herein. In some embodiments, the compounds are for use in methods as disclosed herein.

[0233] Combination therapy Formula (I'), (I), (II), (III), (IV), or any related formula such as formula (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af Compounds of (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, may be used in combination with or concurrently with at least one other active agent, such as an anticancer agent or regimen.

[0234] In some implementations, treatment may include administration of formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae) Compounds of (I-af), (I-ag), (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or a pharmaceutically acceptable salt thereof, in combination with one or more additional therapeutic agents known for treating diseases or ailments (e.g., cancer). Representative examples of additional active agents and treatment regimens include radiotherapy, chemotherapy agents, immunomodulators, therapeutic antibodies, and CAR-T therapy.

[0235] medicine box The compounds and their pharmaceutically acceptable salts and stereoisomers, and / or compositions comprising them, can be assembled into a pillbox or pharmaceutical system. Pillboxes or pharmaceutical systems according to this aspect of the invention include carriers or packaging, such as boxes, cartons, tubes, etc., having one or more tightly confined containers, such as vials, tubes, ampoules, or bottles, containing formulas (I'), (I), (II), (III), (IV), or any related formulas such as (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (I-aa), (I-ab), (I-ac), (I-ad), (I-ae), (I-af), (I-ag). Compounds of (II-a), (II-b), (II-c), (II-d), (II-e), (II-f), (II-g), (IV-a), (IV-b), (IV-c), (IV-d), (IV-e), (IV-f), (IV-g), (IV-h), (IV-j), (IV-k), or (IV-l), or their tautomers or stereoisomers, or pharmaceutical compositions thereof. The kit or pharmaceutical system of the present invention may also include printed instructions for use of the compounds and compositions. In one aspect, the kit contains a compound of the present disclosure or a pharmaceutically acceptable salt thereof, and a label and / or instructions for use of the compound to treat the diseases or conditions described herein. The kit may contain a unit dosage form of the compound.

[0236] List of implementation plans The following embodiments represent some aspects of the present invention.

[0237] Listed implementation scheme 1. A compound of formula (I) (I), Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Q is R Q Or ring 5, Among them, ring 5 is selected from the following groups: arbitrarily selected by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally with one or more R 5b Substituted 5 to 12 heteroaryl groups or Q has the formula (i) , (i) in: Ring A can be selected from the following groups: , , and Each of them is optionally controlled by one or more Cs 1-4 Alkyl or halogenated groups; X is a bond, -O-, -NH-, or -NHC(O)-; Ring B can be selected from the following groups: , , , , , and Each of them is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a bond, -O-, -NH-, or -NHC(O)-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. C Substituted 4- to 12-membered heterocyclic groups; The connector is a key, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**,in *Indicates the connection point with ring C when ring C exists, and *Indicates the connection point with W when ring C does not exist; and **Indicates the connection point with U when ring 2 exists, and** indicates the connection point with V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ); When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a bond or C(O); Ring 2 is optional, and when present, is selected from the following groups: optionally by one or more R... 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The 6 to 12 aryl groups are replaced, and optionally by one or more R groups. 2b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R)y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4Halogenated groups; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a cyclic lactam, or (b) V contains amides, or (c) V together with the atoms of ring 1, ring 2 or ring 5 to which it is attached forms an amide; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 is present and is not a cycloalkyl or tetrahydropyranyl group.

[0238] Example 2. The compound as described in Example 1, or its tautomers or stereoisomers, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Ring 1 is a 4- to 8-membered cycloalkyl group, a saturated 4- to 8-membered heterocyclic group containing at least one cyclic ether, a saturated 4- to 8-membered heterocyclic group containing at least one cyclic amine, or a saturated 4- to 8-membered heterocyclic group containing a cyclic amide, each optionally being construed with one or more R groups. 1 replace; And among them: (i) When ring 1 is optionally bounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amine, then V is attached to the cyclic nitrogen atom of ring 1 and is -C(O)- or -C. 1-4 Alkylene-C(O)-#, where # indicates the junction with ring 1; (ii) When ring 1 is optionally bounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amide, then V is attached to the cyclic nitrogen atom of ring 1 and is a bond or -C. 1-4 alkylene-; and (iii) When ring 1 is C 4-8 A cycloalkyl or 4- to 8-membered heterocyclic ring comprising at least one cyclic ether and not containing a cyclic amine or cyclic amide, each optionally constituting one or more R 1 When replacing, then: (a) V is -C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; or (b) Ring 5 is optionally bounded by one or more R 5a Substituted 4- to 12-membered heterocyclic groups, where V is -C(O)- and attached to a cyclic nitrogen atom in ring 5; or (c) Ring 2 is optionally bounded by one or more R 2a The substituted 4 to 12-membered heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2.

[0239] Example 3. The compound as described in Example 1 or 2, wherein R is chlorine.

[0240] Example 4. The compound as described in Example 1 or 2, wherein R is fluorine.

[0241] Example 5. The compound as described in any one of Examples 1-4, wherein ring 3 is optionally surrounded by one or more R 3aSubstituted 4- to 6-membered heterocyclic groups.

[0242] Example 6. The compound as described in Example 5, wherein ring 3 is... , , or Each of them is optionally controlled by one or more R 3a replace.

[0243] Example 7. The compound as described in any one of Examples 1-4, wherein ring 3 is optionally surrounded by one or more R 3b Substituted phenyl groups.

[0244] Example 8. The compound of any one of the listed embodiments 1-4, wherein ring 3 is optionally surrounded by one or more R 3b Substituted 5- to 6-membered heteroaryl groups.

[0245] Example 9. The compound as described in Example 8, wherein ring 3 is... , Each of them is optionally controlled by one or more R 3b replace.

[0246] Example 10. The compound of any one of the listed embodiments 1-7, wherein ring 4 is absent.

[0247] Example 11. The compound of any one of the examples 1-7, wherein ring 4 is a 3- to 6-membered cycloalkyl group.

[0248] Example 12. The compound as described in example 11, wherein ring 4 is optionally surrounded by one or more R 4a Substituted cyclobutyl, cyclopentyl or cyclohexyl.

[0249] Example 13. The compound as described in any one of Examples 1-9, wherein ring 4 is optionally surrounded by one or more R 4a Substituted 4- to 6-membered heterocyclic groups.

[0250] Example 14. The compound as described in example 13, wherein ring 4 is... , or Each of them is optionally controlled by one or more R 4a replace.

[0251] Example 15. A compound as described in any one of the listed embodiments 1-9, wherein ring 4 is optionally surrounded by one or more R4b Substituted phenyl groups.

[0252] Example 16. A compound as described in any one of the listed embodiments 1-9, wherein ring 4 is optionally surrounded by one or more R 4b Substituted 5- to 6-membered heteroaryl groups.

[0253] Example 17. The compound as described in example 16, wherein ring 4 is optionally surrounded by one or more R 4b Replacement .

[0254] Example 18. A compound as described in any one of examples 1-4, wherein ring 3 is optionally R 3b The substituted phenyl group, and ring 4 is optionally replaced by R. 4b Substituted phenyl groups.

[0255] Example 19. The compound as described in any one of the listed embodiments 1-4, wherein ring 3 is optionally R 3b The substituted phenyl group, or ring 4, is optionally R 4b Substituted phenyl groups.

[0256] 20. The compound as described in any one of the listed embodiments 1-4, wherein... Ring 3 can be freely grouped into the following groups: optionally by one or more R 3a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 3a The substituted 4- to 6-membered he...

Claims

1. A compound of formula (I') (I')， Or its tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: R is a halogroup; Ring 4 is optional, and when present, is a single ring selected from the group consisting of: optionally bounded by one or more R... 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, optionally replaced by one or more R 4b Substituted phenyl groups, and optionally with one or more R groups 4b Substituted 5- to 6-membered heteroaryl groups; Ring 3 is a single ring selected from the following groups: optionally bounded by one or more R... 3a Substituted 3- to 6-membered cycloalkyl groups; optionally with one or more R 3a Substituted 4- to 6-membered heterocyclic groups; optionally replaced by one or more R 3b Substituted phenyl; or optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; Ring 1 is a 4- to 8-membered cycloalkyl group or a saturated 4- to 8-membered heterocyclic group, each optionally separated by one or more R groups. 1 replace; V is a key, -C 1-4 Alkylene-, -C(O)-, -C(O)O-#, -OC(O)# -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-OC(O)N(R V )-#、-N(R V -C(O)O#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; and Q is R Q Or ring 5, Among them, ring 5 is selected from the following groups: arbitrarily selected by one or more R 5a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 5a The substituted 4- to 12-membered heterocyclic group, and optionally replaced by one or more R 5b Substituted 5- to 12-membered heteroaryl groups; or Q has the formula (i) ，(i) in: Ring A can be selected from the following groups: , , and Each of them is optionally controlled by one or more Cs 1-4 Alkyl or halogenated groups; X is a bond, -O-, -NH-, or -NHC(O)-; Ring B can be selected from the following groups: , , , , , and Each of them is optionally bound by one or more halogen groups, C 1-4 Alkyl, C 1-4 Halogenated alkyl or OH-substituted, wherein R D For H or C 1-4 Alkyl group, where # indicates connection to X; W represents a bond, -O-, -NH-, or -NHC(O)-; The ring C is optional, and when it exists, it is optionally bounded by one or more R. C Substituted 4- to 12-membered heterocyclic groups; The connectors are key, -O-, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**,in *Indicates the connection point with ring C when ring C exists, and *Indicates the connection point with W when ring C does not exist; and **Indicates the connection point with U when ring 2 exists, and** indicates the connection point with V when ring 2 does not exist; L 1 For key or C 1-6 Alkylene; L 2 To be optionally used by one or more R L Substituted 3- to 10-membered cycloalkyl groups or 4- to 12-membered heterocyclic groups; and L 3 C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)-C 1-10 Alkylene, C(O)-C 1-10 Alkylene-N(R) y ), C(O)N(R y )-C 1-10 Alkylene or C(O)N(R) y )-C 1-10 Alkylene-N(R) y ); When ring 2 does not exist, U does not exist, and when ring 2 exists, U is a bond or C(O); Ring 2 is optional, and when present, is selected from the following groups: optionally by one or more R... 2a The substituted 3- to 10-membered cycloalkyl group, optionally with one or more R 2a The substituted 4- to 12-membered heterocyclic group, optionally replaced by one or more R 2b The 6 to 12 aryl groups are replaced, and optionally by one or more R groups. 2b Substituted 5- to 12-membered heteroaryl groups; Each R 1 Independently oxo, halogen, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Halogenated groups, SO2R x SO2N(R) y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C(O)N(R) y )(R, z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)R w C 1-4 Hydroxyalkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R C Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R L Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R Q Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R V Independently H, halogen, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R w Independently a 3- to 10-membered cycloalkyl group, optionally substituted with a halogen group, or optionally substituted with a hydroxyl group, C 1-4 Hydroxyalkyl or C 1-4 Aminoalkyl-substituted 4- to 12-membered heterocyclic groups; Each R x Independently for C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 alkyl; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl, 3- to 10-membered cycloalkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a lactam, or (b) V contains amides or carbamates, or (c) V together with the atoms of the ring 1, ring 2 or ring 5 to which it is attached forms an amide or carbamate; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 exists and is not a cycloalkyl or tetrahydropyranyl group; and When ring 1 is an 8-membered heterocyclic group, ring 3 is a CN-substituted phenyl group, ring 4 is absent, and Q is R. Q And when V is -OC(O)#, then R Q Not schuding.

2. The compound of claim 1, or its tautomers or stereoisomers, or a pharmaceutically acceptable salt of any of the foregoing, wherein: V is a key, -C 1-4 Alkylene-, -C(O)-, -C 1-4 Alkylene-C(O)-#、-C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; The connector is a key, C 1-10 Alkylene, C 1-10 Alkylene-N(R) y ), C(O)C 1-10 Alkylene, C(O)C 1-10 Alkylene-N(R) y ), C(O)N(R y C 1-10 Alkylene, C(O)N(R) y C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)C 1-10 Alkylene, C 1-6 Alkylene-C(O)C 1-10 Alkylene-N(R) y C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene, C 1-6 Alkylene-C(O)N(R) y )-C 1-10 Alkylene-N(R) y ), or has the formula *-L 1 -L 2 -L 3 -**, Each R 2a R 3a R 4a and R 5a Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl, C 1-4 Alkylene-S(O) n R x Or oxy group; Each R 2b R 3b R 4b and R 5b Independently halogenated, C 1-4 Alkyl, C 1-4 Halogenated groups, OH, C 1-4 Alkoxy, C 1-4 Haloalkoxy, C(O)C 1-4 Alkyl, C(O)N(R) y (R) z ), CN, N(R) y )C(O)C 1-4 Alkyl, N(R) y )C(O)C 1-4 Alkyl halides, S(O) n R x S(O) n N(R y (R) z C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-N(R) y )-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n R x ; Each R V Independent of halogen group, OH, C 1-4 Alkyl or C 1-4 Halogenated groups; Each R y and R z Independently for H and C 1-4 Alkyl, C 1-4 Halogenated, C 1-4 Alkylene-OC 1-4 Alkyl, C 1-4 Alkylene-NH-C 1-4 Alkyl, C 1-4 Alkylene-N(C) 1-4 alkyl)-C 1-4 Alkyl or C 1-4 Alkylene-S(O) n -C 1-4 Alkyl; and Each n is independently 0, 1, or 2; in: (a) Ring 1 contains a lactam, or (b) V contains amides, or (c) V together with the atoms of ring 1, ring 2 or ring 5 to which it is attached forms an amide; And among them: When ring 3 is a 5-membered heteroaryl group, ring 4 exists and is not a cycloalkyl or tetrahydropyranyl group; and When ring 1 is an 8-membered heterocyclic group, ring 3 is a CN-substituted phenyl group, ring 4 is absent, and Q is R. Q And when V is -OC(O)#, then R Q Not schuding.

3. The compound of claim 1 or 2, or its tautomers or stereoisomers, or a pharmaceutically acceptable salt of any of the foregoing, wherein: Ring 1 is a 4- to 8-membered cycloalkyl group, a saturated 4- to 8-membered heterocyclic group containing at least one cyclic ether, a saturated 4- to 8-membered heterocyclic group containing at least one cyclic amine, or a saturated 4- to 8-membered heterocyclic group containing a cyclic amide, each optionally being separated by one or more R 1 replace; And among them: (i) When ring 1 is optionally bounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amine, then V is attached to the cyclic nitrogen atom of ring 1 and is -C(O)- or -C. 1-4 Alkylene-C(O)-#, where # indicates the junction with ring 1; (ii) When ring 1 is optionally bounded by one or more R 1 When the substituted ring is a 4- to 8-membered heterocyclic group containing at least one cyclic amide, then V is attached to the cyclic nitrogen atom of ring 1 and is a bond or -C. 1-4 alkylene-; and (iii) When ring 1 is C 4-8 A cycloalkyl or 4- to 8-membered heterocyclic ring comprising at least one cyclic ether and not containing a cyclic amine or cyclic amide, each optionally constituting one or more R 1 When replacing, then: (a) V is -C(O)N(R) V )-#、-N(R V )C(O)-#、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where # indicates the connection point with ring 1; or (b) Ring 5 is optionally bounded by one or more R 5a Substituted 4- to 12-membered heterocyclic groups, where V is -C(O)- and attached to a cyclic nitrogen atom in ring 5; or (c) Ring 2 is optionally bounded by one or more R 2a The substituted 4 to 12-membered heterocyclic group, and V is -C(O)- and attached to the cyclic nitrogen atom of ring 2.

4. The compound according to any one of claims 1-3, wherein R is chlorine.

5. The compound according to any one of claims 1-3, wherein R is fluorine.

6. The compound according to any one of claims 1-5, wherein ring 3 is optionally separated by one or more R 3a Substituted 4- to 6-membered heterocyclic groups.

7. The compound of claim 6, wherein ring 3 is , , or Each of them is optionally controlled by one or more R 3a replace.

8. The compound according to any one of claims 1-5, wherein ring 3 is optionally separated by one or more R 3b Substituted phenyl groups.

9. The compound according to any one of claims 1-5, wherein ring 3 is optionally separated by one or more R 3b Substituted 5- to 6-membered heteroaryl groups.

10. The compound of claim 9, wherein ring 3 is , Each of them is optionally controlled by one or more R 3b replace.

11. The compound according to any one of claims 1-8, wherein ring 4 is absent.

12. The compound according to any one of claims 1-8, wherein ring 4 is a 3- to 6-membered cycloalkyl group.

13. The compound of claim 12, wherein ring 4 is cyclobutyl, cyclopentyl, or cyclohexyl, optionally separated by one or more R 4a replace.

14. The compound according to any one of claims 1-10, wherein ring 4 is optionally separated by one or more R 4a Substituted 4- to 6-membered heterocyclic groups.

15. The compound of claim 14, wherein ring 4 is , or Each of them is optionally controlled by one or more R 4a replace.

16. The compound of any one of claims 1-10, wherein ring 4 is optionally separated by one or more R 4b Substituted phenyl groups.

17. The compound according to any one of claims 1-10, wherein ring 4 is optionally separated by one or more R 4b Substituted 5- to 6-membered heteroaryl groups.

18. The compound of claim 17, wherein ring 4 is optionally separated by one or more R 4b Replacement .

19. The compound according to any one of claims 1-5, wherein ring 3 is optionally R 3b The substituted phenyl group, and ring 4 is optionally replaced by R. 4b Substituted phenyl groups.

20. The compound according to any one of claims 1-5, wherein ring 3 is optionally R 3b The substituted phenyl group, or ring 4, is optionally R 4b Substituted phenyl groups.

21. The compound according to any one of claims 1-5, wherein Ring 3 can be freely grouped into the following groups: optionally by one or more R 3a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 3a The substituted 4- to 6-membered heterocyclic group, and optionally with one or more R 3b Substituted 5- to 6-membered heteroaryl groups; and Ring 4 can be freely grouped into the following groups: optionally by one or more R 4a The substituted 3- to 6-membered cycloalkyl group, optionally with one or more R 4a The substituted 4- to 6-membered heterocyclic group, and optionally with one or more R 4b Substituted 5- to 6-membered heteroaryl groups.

22. The compound according to any one of claims 1-10 or 14-21, wherein ring 1 is , , , , , Each of them is optionally controlled by one or more R 1 Replace, where # indicates that it is connected to V.

23. The compound of claim 22, wherein... Ring 1 is or Each of them is optionally controlled by one or more R 1 Replace; and V is -C(O)N(R) V )-、-N(R V )C(O)-、-C 1-4 Alkylene-C(O)N(R) V -# or -C 1-4 Alkylene-N(R) V )C(O)-#, where ## indicates the connection point with ring 1.

24. The compound of claim 22, wherein... Ring 1 is or Each of them is optionally controlled by one or more R 1 Replace, where # indicates connection to V; and V is -C(O)- or -C 1-4 Alkylene-C(O)-#, where # indicates attachment to ring 1.

25. The compound of claim 22, wherein... Ring 1 is , Each of them is optionally controlled by one or more R 1 Replace, where # indicates connection to V; and V is a key or -C 1-4 Alkylene-.

26. The compound according to any one of claims 1-10 or 14-25, wherein Q is R Q .

27. The compound of claim 26, wherein R Q It can be H, methyl, or acetyl.

28. The compound according to any one of claims 1-10 or 14-25, wherein Q is ring 5 and the compound has formula (II): (II), Or its tautomers or stereoisomers, or a pharmaceutically acceptable salt of any of the foregoing.

29. The compound according to any one of claims 1-10 or 14-25, wherein Q has formula (i) and the compound has formula (IV): (IV), Or its tautomers or stereoisomers, or a pharmaceutically acceptable salt of any of the foregoing.

30. The compound of claim 29, wherein ring A is Optionally C 1-4 Alkyl or halogenated substitutions.

31. The compound of claim 29 or 30, wherein X is a bond or -NH-.

32. The compound according to any one of claims 29-31, wherein ring B is , or Each of them is optionally replaced by one or more halogen groups or OH groups, wherein R D For H or C 1-4 alkyl.

33. The compound according to any one of claims 29-32, wherein W is a bond or -O-.

34. The compound according to any one of claims 29-33, wherein the ring C is absent.

35. The compound according to any one of claims 29-33, wherein the ring C is , or Each of them is optionally controlled by one or more R C replace.

36. The compound according to any one of claims 29-35, wherein the linker is a bond, C 1-10 Alkylene or C(O)C 1-10 Alkylene.

37. The compound according to any one of claims 29-36, wherein ring 2 is present and U is a bond.

38. The compound according to any one of claims 29-37, wherein ring 2 is optionally separated by one or more R 2a Replaced 4- to 12-membered heterocyclic groups.

39. The compound according to any one of claims 1-23 or 26-38, wherein R V For H.

40. The compound according to any one of claims 29-37 or 39, wherein ring 2 is optionally separated by one or more R 2a Substituted 3- to 10-membered cycloalkyl groups.

41. The compound according to any one of claims 29-39, wherein ring 2 is , , or Each of them is optionally controlled by one or more R 2a Replace, where # indicates that it is connected to V.

42. The compound according to any one of claims 29-39 or 41, wherein ring 2 is , or Each of them is optionally controlled by one or more R 2a Replace, where # indicates that it is connected to V.

43. The compound of claim 42, wherein ring 2 is .

44. The compound of claim 43, wherein V is -C(O)- and ring 1 is piperidinyl.

45. The compound of claim 41 or 42, wherein ring 2 is or Each of them is optionally controlled by one or more R 2a Replace, where # indicates that it is connected to V.

46. ​​The compound of claim 45, wherein V is -C(O)- and ring 1 is cyclohexyl.

47. The compound of claim 45, wherein V is -C 1-4 Alkyl-C(O)- and ring 1 is piperidinyl.

48. The compound according to any one of claims 27-35, wherein ring 2, ring V and ring 1 are formed together: , or .

49. The compound of claim 48, wherein ring 2, ring V and ring 1 are formed together: 、 、 or .

50. The compound of claim 40, wherein ring 2 is optionally surrounded by one or more R 2a Substituted cyclohexyl groups.

51. The compound of claim 50, wherein ring 2 is optionally surrounded by one or more R 2a Replacement .

52. The compound of claim 50 or 51, wherein V is -C(O)N(R) V )-#, where # indicates the connection point with ring 1, and ring 1 is a cyclohexyl group.

53. The compound according to any one of claims 50-52, wherein ring 2, V and ring 1 are formed together: .

54. The compound of claim 1, wherein the compound is selected from the compounds provided in Tables 1 and 2, their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.

55. The compound of claim 54, wherein the compound is selected from the compounds provided in Table 1, their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.

56. The compound of claim 54, wherein the compound is selected from the compounds provided in Table 2, their tautomers or stereoisomers, or pharmaceutically acceptable salts of any of the foregoing.

57. A pharmaceutical composition comprising the compound of any one of claims 1-56, its tautomer or stereoisomer, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

58. The pharmaceutical composition of claim 57, wherein the compound is any one of claims 26-28 or 55, its tautomers or stereoisomers, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient.

59. The pharmaceutical composition of claim 57, wherein the compound is any one of claims 29-53 or 56, its tautomers or stereoisomers, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable excipient.

60. A method of treating a disease or condition associated with PIP4K2C, the method comprising administering to a subject the compound of any one of claims 1-56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 57.

61. A method of treating a disease or condition by modulating the level or activity of PIP4K2C, the method comprising administering to a subject the compound of any one of claims 1-56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 57.

62. The method of claim 61, wherein the method modulates the activity of PIP4K2C, and wherein the method comprises administering to the subject the compound of any one of claims 26-28 or 55, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 58.

63. The method of claim 61, wherein the method regulates the level of PIP4K2C, and wherein the method comprises administering to the subject the compound of any one of claims 29-53 or 56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 59.

64. The method of any one of claims 60-63, wherein the disease or condition is cancer, immunodeficiency, autoimmune disease, infectious disease, or a combination thereof.

65. The method of claim 64, wherein the cancer is brain cancer, bladder cancer, breast cancer, triple-negative breast cancer, cervical cancer, colorectal cancer, colorectal cancer with MSI, colorectal cancer with MSS, gastric cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, leukemia, lung cancer, small cell lung cancer, non-small cell lung cancer, lymphoma, melanoma, Merck cell carcinoma, multiple myeloma, pancreatic duct carcinoma, or renal cell carcinoma.

66. The method of claim 65, wherein the cancer is brain cancer, breast cancer, triple-negative breast cancer, colorectal cancer, colorectal cancer with MSI, colorectal cancer with MSS, or non-small cell lung cancer.

67. The method of any one of claims 60-63, wherein the disease or condition is a neurodegenerative disease.

68. A method for treating a viral infection by modulating PIP4K2C levels, the method comprising administering to a subject the compound of any one of claims 29-53 or 56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 59.

69. A method for treating necrotizing soft tissue infection (NSTI), the method comprising administering to a subject the compound of any one of claims 1-56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 57.

70. A method for regulating the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C, the method comprising administering to a subject the compound of any one of claims 1-56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any one of the foregoing, or the pharmaceutical composition of claim 57.

71. The compound of any one of claims 1-56, or the pharmaceutical composition of claim 57, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, for the treatment of a subject in need of a disease or condition related to PIP4K2C.

72. The compound of any one of claims 1-56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 57, for treating a disease or condition by modulating the level or activity of PIP4K2C in a subject of need.

73. The compound for use as claimed in claim 72, wherein the compound for use modulates the activity of PIP4K2C, and wherein the compound for use is the compound of any one of claims 26-28 or 55, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 58.

74. The compound for use as claimed in claim 72, wherein the compound for use regulates the level of PIP4K2C, and wherein the compound for use is the compound of any one of claims 29-53 or 56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 59.

75. The compound for use according to any one of claims 71-74, wherein the disease or condition is cancer, immunodeficiency, autoimmune disease, infectious disease, or a combination thereof.

76. The compound for use as claimed in claim 75, wherein the cancer is brain cancer, bladder cancer, breast cancer, triple-negative breast cancer, cervical cancer, colorectal cancer, colorectal cancer with MSI, colorectal cancer with MSS, gastric cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, leukemia, lung cancer, small cell lung cancer, non-small cell lung cancer, lymphoma, melanoma, Merck cell carcinoma, multiple myeloma, pancreatic duct carcinoma, or renal cell carcinoma.

77. The compound for use as claimed in claim 76, wherein the cancer is brain cancer, breast cancer, triple-negative breast cancer, colorectal cancer, colorectal cancer with MSI, colorectal cancer with MSS, or non-small cell lung cancer.

78. The compound for use according to any one of claims 71-74, wherein the disease or condition is a neurodegenerative disease.

79. The compound of any one of claims 29-53 or 56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 59, for treating a viral infection by modulating the PIP4K2C level in a subject in need.

80. The compound of any one of claims 1-56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 57, for the treatment of a subject in need of necrotizing soft tissue infection (NSTI).

81. The compound of any one of claims 1-56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or the pharmaceutical composition of claim 57, for regulating the level or activity of at least one of PIP4K2A, PIP4K2B and PIP4K2C in a subject of need.

82. Use of any compound, tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, as described in any one of claims 1-56, for the manufacture of an agent for the treatment of a subject in need of a disease or condition related to PIP4K2C.

83. The use of any compound, tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, as described in any one of claims 1-56, in the manufacture of an agent for treating a disease or condition by modulating the level or activity of PIP4K2C in a subject of need.

84. The use as claimed in claim 83, wherein the use modulates the activity of PIP4K2C, and wherein the compound is the compound of any one of claims 26-28 or 55, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

85. The use as claimed in claim 83, wherein the use regulates the level of PIP4K2C, and wherein the compound is any one of claims 29-53 or 56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

86. The use as claimed in any one of claims 82-85, wherein the disease or condition is cancer, immunodeficiency, autoimmune disease, infectious disease, or a combination thereof.

87. The use as described in claim 86, wherein the cancer is brain cancer, bladder cancer, breast cancer, triple-negative breast cancer, cervical cancer, colorectal cancer, colorectal cancer with MSI, colorectal cancer with MSS, gastric cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, leukemia, lung cancer, small cell lung cancer, non-small cell lung cancer, lymphoma, melanoma, Merck cell carcinoma, multiple myeloma, pancreatic duct carcinoma, or renal cell carcinoma.

88. The use as described in claim 87, wherein the cancer is brain cancer, breast cancer, triple-negative breast cancer, colorectal cancer, colorectal cancer with MSI, colorectal cancer with MSS, or non-small cell lung cancer.

89. The use as claimed in any one of claims 82-85, wherein the disease or condition is a neurodegenerative disease.

90. Use of the compound, tautomer or stereoisomer or any of the compounds described in any one of claims 29-53 or 56, or a pharmaceutically acceptable salt thereof, for the manufacture of an agent for treating viral infections by modulating the PIP4K2C level in a subject of need.

91. Use of the compound of any one of claims 1-56, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, for the manufacture of an agent for the treatment of necrotizing soft tissue infection (NSTI) in a subject of need.

92. The use of any compound, tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, as claimed in any one of claims 1-56, for the manufacture of an agent for regulating the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C in a subject of need.

93. A pillbox comprising (i) a compound of any one of claims 1-56, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 57, and (ii) instructions for use in treating a PIP4K-mediated disease, condition or disorder in an individual in need.

94. The method of claim 65 or 66, wherein the cancer is brain cancer.

95. The method of any one of claims 65, 66 or 94, wherein the brain cancer is a glioma or glioblastoma.

96. The method of any one of claims 65, 66 or 94, wherein the brain cancer is a brainstem glioma, a gestational trophoblastic glioma, a cerebellar astrocytoma, a cerebral astrocytoma / malignant glioma, an ependymoma, a medulloblastoma, a supratentorial primitive neuroectodermal tumor, or a visual pathway or hypothalamic glioma.

97. The method of claim 65 or 66, wherein the cancer is colorectal cancer.

98. The method of any one of claims 65, 66 or 97, wherein the colorectal cancer is colorectal cancer, colorectal cancer with MSI or colorectal cancer with MSS.

99. The method of any one of claims 65, 66 or 97, wherein the colorectal cancer is associated with a hereditary syndrome.

100. The method of claim 65 or 66, wherein the cancer is non-small cell lung cancer.

101. The compound for use as claimed in claim 76 or 77, wherein the cancer is brain cancer.

102. The compound for use as claimed in any one of claims 76, 77 or 101, wherein the brain cancer is a glioma or glioblastoma.

103. The compound for use as claimed in any one of claims 76, 77 or 101, wherein the brain cancer is a brainstem glioma, a gestational trophoblastic glioma, a cerebellar astrocytoma, a cerebral astrocytoma / malignant glioma, an ependymoma, a medulloblastoma, a supratentorial primitive neuroectodermal tumor, or a visual pathway or hypothalamic glioma.

104. The compound for use as claimed in claim 76 or 77, wherein the cancer is colorectal cancer.

105. The compound for use as claimed in any one of claims 76, 77 or 104, wherein the colorectal cancer is colorectal cancer, colorectal cancer with MSI or colorectal cancer with MSS.

106. The compound for use as claimed in any one of claims 76, 77 or 104, wherein the colorectal cancer is associated with a hereditary syndrome.

107. The compound for use as claimed in claim 76 or 77, wherein the cancer is non-small cell lung cancer.

108. The use as described in claim 87 or 88, wherein the cancer is brain cancer.

109. The use as described in any one of claims 87, 88 or 108, wherein the brain cancer is a glioma or glioblastoma.

110. The use as described in any one of claims 87, 88 or 108, wherein the brain cancer is a brainstem glioma, a gestational trophoblastic glioma, a cerebellar astrocytoma, a cerebral astrocytoma / malignant glioma, an ependymoma, a medulloblastoma, a supratentorial primitive neuroectodermal tumor, or a visual pathway or hypothalamic glioma.

111. The use as described in claim 87 or 88, wherein the cancer is colorectal cancer.

112. The use as described in claim 87, 88 or 111, wherein the colorectal cancer is colorectal cancer, colorectal cancer with MSI or colorectal cancer with MSS.

113. The use as described in claim 87, 88 or 111, wherein the colorectal cancer is associated with a hereditary syndrome.

114. The use as described in claim 87 or 88, wherein the cancer is non-small cell lung cancer.

115. The method of any one of claims 60-63, wherein the disease or condition is related to phosphatidylinositol phosphatase. FIG4 It is associated with loss of function mutations.

116. The method of claim 115, wherein the disease or condition is Charcot-Marie-Tooth disease.

117. The method of claim 115 or 116, wherein the disease or condition is Charcot-Marie-Tooth disease type 4J.

118. The compound for use according to any one of claims 71-74, wherein the disease or condition is related to phosphatidylinositol phosphatase. FIG4 It is associated with loss of function mutations.

119. The compound for use as claimed in claim 118, wherein the disease or condition is Charcot-Marie-Tooth disease.

120. The compound for use as claimed in claim 118 or 119, wherein the disease or condition is Charcot-Marie-Tooth disease type 4J.

121. The use as described in any one of claims 82-85, wherein the disease or condition is related to phosphatidylinositol phosphatase. FIG4 It is associated with loss of function mutations.

122. The use as claimed in claim 121, wherein the disease or condition is Charcot-Marie-Tooth disease.

123. The use as described in claim 121 or 122, wherein the disease or condition is Charcot-Marie-Tooth disease type 4J.

124. The method of claim 68, wherein the compound, or its tautomer or stereoisomer, or a pharmaceutically acceptable salt thereof, is administered in combination with a vaccine for viral infection to enhance the immune response.

125. The compound for use as claimed in claim 79, wherein the compound, or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt thereof, is administered in combination with a vaccine for viral infection to enhance the immune response.

126. The use as described in claim 90, wherein the agent is administered in combination with a vaccine for viral infection to enhance the immune response.

Images