SOS1 decomposition agent, its manufacturing method and application

Abstract

The present invention discloses an SOS1 decomposition agent and its preparation method and application. Specifically, the present invention discloses a compound of formula I, SLE(I), in which L is a linking chain connecting S and E via a covalent bond, and E is a small molecule ligand of the E3 ubiquitin ligase complex. The compound of formula I of the present invention can degrade and / or inhibit intracellular SOS1 protein, and can be used to treat and / or prevent diseases or conditions related to SOS1-mediated or SOS1-Ras or SOS1-Rac interactions.

Description

[Technical Field]

[0001] The present invention belongs to the field of pharmaceutical technology, and specifically relates to an SOS1 degrading agent, a method for producing the same, and its application as a therapeutic agent for preventing and / or treating cancer. [Background technology]

[0002] The SOS1 (son of sevenless homolog 1) protein is a regulatory protein widely expressed in cells. As a key protein in signal transduction pathways, SOS1 plays an important regulatory role in many intracellular signal transduction pathways, including the regulation of the Ras and Rac signaling pathways. SOS1 consists of 1,333 amino acids and contains a proline-rich domain (PxxP) at its C-terminus. This domain binds to growth factor receptor-bound protein 2 (Grb2) in the Ras signaling pathway. The formation of a complex between Grb2 and SOS1 transports SOS1 to the plasma membrane, where it catalyzes the binding of Ras with GTP, promoting Ras activation and activating multiple downstream signaling pathways, including Ras-Raf-Mek-Erk and Ras-PI3K-AKT-mTOR. PxxP can also bind to the SH3 (Src homology 3) domain of proteins such as E3B1 in the Rac signaling pathway to form an EPS8-E3B1-SOS1 complex, which then links to actin filaments via EPS8, causing GTP exchange and activating Rac, which in turn activates signaling pathways such as JNK and MAPK.

[0003] Mutant Ras genes are believed to be the main oncogene responsible for the high incidence of human cancers, and studies have shown that 20-30% of tumor patients have Ras mutations, of which KRas mutations account for 85%, NRas mutations for 12% and HRas mutations for 3%. However, because GTP has picomolar affinity for the binding site and there are no other suitable binding pockets on the smooth surface of the Ras protein, it is considered extremely difficult to directly inhibit Ras activity.

[0004] Abnormal expression or mutation of SOS1 is also closely related to the development of clinical diseases. Research has shown that both NS and CFC patients have SOS1 mutations. HGF1 is a rare autosomal dominant genetic disease, the etiology of which is related to mutations in the PxxP domain of SOS1. Abnormal expression or mutation of SOS1 is also related to the development of cancer.

[0005] WO2018172250A1, WO2020173935A1, WO2019201848A1, WO2020180768A1, WO2020180770A1, WO2019122129A1 and EP3558979A1 disclose several types of SOS1 inhibitors, but so far there have been no related reports of SOS1 degraders. Proteolysis targeting chimeras (PROTACs) are a distinct technology from traditional small molecule inhibitors. While traditional small molecule inhibitors typically require target protein activation by targeting the active site, PROTACs are heterobifunctional molecules that combine a small molecule inhibitor capable of targeting a target protein at one end with an E3 ubiquitin ligase ligand at the other end. These bifunctional molecules recognize the target protein and the E3 ubiquitin ligase in vivo, bringing the target protein into proximity with the E3 ubiquitin ligase to form a ternary complex, ubiquitinating the target protein and subsequently degrading it via the ubiquitin-protease pathway in vivo. Compared to traditional small molecule inhibitors, PROTACs only require the target protein to be brought into proximity with the E3 ubiquitin ligase for substrate degradation. This mechanism of action makes this technology applicable to some undruggable targets. On the other hand, even after the target protein is degraded, the PROTAC molecule can be released and continue to participate in the degradation process of the next protein. This catalytic degradation action allows for efficient degradation with a relatively low PROTAC drug dose. Furthermore, while traditional small molecule inhibitors are prone to drug resistance due to point mutations, which cause them to lose their inhibitory effect on the target, PROTACs can directly degrade target proteins, thereby avoiding drug resistance caused by point mutations to some extent. Therefore, compared with traditional small molecule inhibitors, the use of PROTAC technology in the research and development of new small drug molecules is highly advantageous and feasible. Summary of the Invention

[0006] The present invention provides compounds of formula I, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof: SLE I where: S is a small molecule compound capable of inhibiting SOS1 protein activity or binding to SOS1 protein, L is a linking chain connecting S and E via a covalent bond, E is a small molecule ligand of the E3 ubiquitin ligase complex.

[0007] The present invention provides compounds of formula I, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof: SLE I S, L and E are as defined below.

[0008] Preferably, in certain embodiments of the present invention, S is S1, [ka] Here, in the above S1, R1 is hydrogen, halogen, -OH, -CN, -NO2, a C1-C6 alkylmercapto group, or -NR a R b and R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R1 is a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkoxy group, a C3-C6 heterocycloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, a C4-C8 cycloalkenyl group, a 4- to 7-membered heterocycloalkyl group, a 5- to 10-membered heterocycloalkenyl group, a spiroheterocycloalkyl group, a fused heterocycloalkyl group, a bridged heterocycloalkyl group, a phenyl group, a heteroaryl group, a C1-C6 haloalkyl group, -COOH, -COOR c and R c is a -C1-C6 alkyl group, a C3-C6 alkenyl group, a C3-C6 alkynyl group, a C3-C8 cycloalkyl group or a -C4-C8 cycloalkenyl group, R1 is -NS(O)(R d )(R e ) and the above R d and R e each independently represents a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, a C4-C8 cycloalkenyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group; R1 is -NHC(O)-(C1-C6 alkyl), -NHC(O)-NR a R b and the above R a and R b are each independently hydrogen, a —C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R1 is -NH-(CH2) k -NH-C(O)-R aa and the above R aa is a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group (e.g., the above R aa is a C1-C6 alkyl group), and k is 1 or 2; R1 is -NH-(CH2) i -R f wherein i is 0, 1 or 2, and R fis a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, or a C1-C6 alkylsulfonyl group, The C1-C6 alkyl group, C1-C6 alkoxy group, 4- to 7-membered heterocycloalkyl group, and heteroaryl group may optionally be selected from the group consisting of halogen, -OH, oxo, -CN, -NO2, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C8 cycloalkyl group, 4- to 7-membered heterocycloalkyl group, C1-C6 alkoxy group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, C1-C6 alkylsulfonyl group, phenyl group, benzyl group, heteroaryl group, -(CH2)-heteroaryl group, -NHC(O)(C1-C6 alkyl), C3-C8 cycloalkoxy group, phenoxy group, heteroaryloxy group, and -NR a R b and R a and R b are each independently selected from hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R1 is -O-(CH2) z -phenyl group, -O-(CH2) z -(4-7 membered heterocycloalkyl), -O-(CH2) z -heteroaryl group, wherein z is 0, 1 or 2, and the phenyl group, heterocycloalkyl group and heteroaryl group are optionally substituted with a group selected from -OH, heterocycloalkyl group or heterocycloalkenyl group, and can be substituted with a methyl group or an oxo group; Or R1 is [ka] and or two adjacent R1's together with the carbon atoms connected thereto form a 5- to 7-membered cycloalkyl group or a 5- to 7-membered heterocycloalkyl group, and x is 1, 2 or 3; A1 is C4-C 12a cycloalkyl group, a heterocycloalkyl group, an aryl group (e.g., a phenyl group), or a heteroaryl group (e.g., a thienyl group); R2 is hydrogen, -OH, oxo, halogen, -CN, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C2-C6 alkenyl group, a -C2-C6 alkynyl group, a -C3-C8 cycloalkyl group, a -C3-C8 cycloalkoxy group, a -C3-C8 halocycloalkoxy group, a -C4-C8 cycloalkenyl group, a 4- to 7-membered heterocycloalkyl group, -O-CH2-4- to 7-membered heterocycloalkyl group, a 5- to 10-membered heterocycloalkenyl group, a spiroheterocycloalkyl group, a fused heterocycloalkyl group, a bridged heterocycloalkyl group, a phenyl group, a heteroaryl group, a -C1-C6 haloalkyl group, a -C1-C6 haloalkoxy group, or a -C1-C6 alkylsulfonyl group; R2 is -NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, or a —C(O)C1-C3 alkyl group; R2 is -C(O)NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R2 is -C(O)OR g and the above R g is hydrogen or a C1-C6 alkyl group, R2 is -OR h and the above R h is a C1-C6 alkyl group, R2 is -(CH2)NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; and w is 1, 2, 3, or 4 (e.g., w is 1, 2, or 3); Above A2(R3) Y is hydrogen, Or A2 is C4-C 12 a cycloalkyl group, a heterocycloalkyl group, an aryl group (e.g., a phenyl group), or a heteroaryl group, and R3 is hydrogen, halogen, -OH, oxo, -CN, -NO2, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, a C4-C8 cycloalkenyl group, a C7-C8 cycloalkynyl group, a 4- to 7-membered heterocycloalkyl group, a 5- to 10-membered heterocycloalkenyl group, a phenyl group, a heteroaryl group, or a C1-C6 haloalkyl group; The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl, and heterocycloalkenyl groups may optionally be selected from the group consisting of halogen, —OH, oxo, —CN, —C1-C6 alkyl, —C1-C6 alkoxy, —C1-C6 haloalkyl, phenyl, heteroaryl, or —C(O)NR i R j and R i and R j are each independently hydrogen or a C1-C6 alkyl group; or the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups are optionally -NR k R l The above R is replaced by k and R l are each independently hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, a C1-C6 alkylsulfonyl group, a phenyl group, a heteroaryl group, -CH2-C(O)-R m , -C(O)R por a 4- to 7-membered heterocycloalkyl group, wherein the alkyl group, alkynyl group, alkenyl group, cycloalkyl group, phenyl group, heteroaryl group, and heterocycloalkyl group are each independently optionally substituted with one, two, or three groups selected from a C1-C6 haloalkyl group, —OH, an oxo group, a phenyl group, —CN, a C1-C6 alkoxy group, or a heteroaryl group, and the heteroaryl group is optionally substituted with a methyl group, and the R m is a bicyclic heteroaryl group, a C1-C6 alkoxy group or -NR n R o and the above R n and R o are each independently hydrogen, a C1-C6 alkyl group, or a phenyl group, the alkyl group being optionally substituted with a C1-C6 alkoxy group or a phenyl group, or -NR n R o is a 4- to 7-membered azacycloalkyl group, which is linked to other parts of the molecule via a N atom and further contains one or more heteroatoms selected from N and O, and R p is selected from a C1-C6 alkoxy group, a C1-C6 alkyl group optionally substituted with 1, 2 or 3 groups selected from —OH or a C1-C6 alkoxy group, a monocyclic or bicyclic heteroaryl group, a 4- to 7-membered heterocycloalkyl group, or R p is -CH2-NR q R r and the above R q and R r are each independently selected from hydrogen, a phenyl group, or a C1-C6 alkyl group optionally substituted with F; or the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups are optionally -NR s R t The above is substituted with -NR s R tis a 4- to 7-membered azacycloalkyl group linked to another part of the molecule through a nitrogen atom or a 6- to 10-membered azaspiroheterocycloalkyl group linked to another part of the molecule through a nitrogen atom, and further contains at most two heteroatoms selected from N or O, and optionally contains -OH, oxo group, C1-C6 alkyl group, C1-C6 hydroxyalkyl group, -C(O)OR z and R z is a C1-C6 alkyl group, halogen, -N(C1-C6 alkyl)2, -CH2N(C1-C6 alkyl)2, -C(O)NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; or R3 is C(O)R v , -C(O)NH2, -C(O)NHR v , -C(O)NR v R w , -C(O)OR v and the above R v and R w are each independently a hydrogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a phenyl group, or -(CH2)2NR x R y and the above R x and R y are each independently hydrogen, a C-C alkyl group, or —(CH)N(CH), Or R3 is -NH2, -NHR z , -NR z R za , -NHC(O)R z , -NHC(O)OR z , -NHS(O)2R z , a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, a spiro heterocycloalkyl group, a fused heterocycloalkyl group, or a bridged heterocycloalkyl group; z and R zaare each independently a C1-C4 alkyl group, a C1-C4 haloalkyl group, or a phenyl group; Or R3 is a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, -O(CH2) s -C3-C8 cycloalkyl group, -O(CH2) s -phenyl group, -O(CH2) s -heterocycloalkyl group, -O(CH2) s -heteroaryl group, where s is 0, 1, 2 or 3; Or R3 is -S(O)2R z , -S(O)2NH2, -S(O)2NHR z , -S(O)NR z R za and the above R z and R za are each independently a C1-C4 alkyl group, a C1-C4 haloalkyl group, or a phenyl group; Y is 0, 1, 2, 3, 4, or 5 (e.g., Y is 0, 1, 2, or 3); L' is a bond, -(CH2) k -, -O(CH2) k -, -(CH2) k -O- or -O-(CH2) k -O- (e.g., L' is a bond, -(CH2) k - or -O(CH2) k -), wherein k is 0, 1, 2 or 3, or L' is -CH=CH-(CH) n wherein n is 0, 1 or 2; R4 and R5 are each independently a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, or a C3-C6 cycloalkoxy group, and the alkyl group, alkoxy group, cycloalkyl group, and cycloalkoxy group are optionally substituted with a cyano group, a hydroxy group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, or a halogen.

[0009] Preferably, in a specific embodiment of the present invention, in the above S1, R4 and R5 are each independently a methyl group.

[0010] In some embodiments, in the definition of each group of S1, a and R b appears at any position, each independently is hydrogen or a C1-C6 alkyl group.

[0011] In some embodiments, in the definition of each group of S1, d and R e appears at any position, each independently is hydrogen or a C1-C6 alkyl group.

[0012] In a specific embodiment of the present invention, in the above S1, R5 is a C1-C6 alkyl group, for example a methyl group.

[0013] In a specific embodiment of the present invention, in the above S1, R4 is a C1-C6 alkyl group, for example a methyl group.

[0014] In certain embodiments of the present invention, in the above S1, R1 is hydrogen or a C1-C6 alkoxy group.

[0015] In certain embodiments of the present invention, in the above S1, A1 is an aryl group or a heteroaryl group.

[0016] In a specific embodiment of the present invention, in the above S1, A1 is an aryl group, for example a phenyl group.

[0017] In a specific embodiment of the present invention, in the above S1, A1 is a heteroaryl group, for example a thienyl group.

[0018] In certain embodiments of the present invention, in the above S1, R2 is hydrogen, halogen, a C1-C6 alkyl group, or a -C1-C6 haloalkyl group.

[0019] In certain embodiments of the present invention, in the above S1, L' is a bond.

[0020] In a specific embodiment of the present invention, in the above S1, A2(R3) Y is hydrogen.

[0021] In a specific embodiment of the present invention, in the above S1, A2 is an aryl group, for example a phenyl group.

[0022] In certain embodiments of the present invention, in the above S1, R3 is hydrogen, halogen or a C1-C6 alkyl group, and the alkyl group is optionally -NR k R l The above R is replaced by k and R l are each independently hydrogen or a C1-C6 alkyl group. In a specific embodiment of the present invention, in the above S7, R3 is hydrogen, F, Cl, a methyl group, or an ethyl group, and the methyl group and ethyl group are -NR k R l The above R is replaced by k is a methyl group or an ethyl group, and R l is hydrogen, a methyl group, or an ethyl group.

[0023] In certain embodiments of the present invention, in the above S1, R3 is hydrogen, Cl, -CH2NHCH3 or -CH2N(CH3)2.

[0024] In a specific embodiment of the present invention, in the above S1, A1 is an aryl group, L' is a bond, A2(R3) Y is hydrogen.

[0025] In certain embodiments of the present invention, in the above S1, A1 is a heteroaryl group, L' is a bond, A2 is an aryl group, and R3 is hydrogen, halogen, or a C1-C6 alkyl group, wherein the alkyl group is optionally -NR k R l The above R is replaced by k and R l are each independently hydrogen or a C1-C6 alkyl group.

[0026] In certain embodiments of the invention, S is S1′, [ka] Here, in the above S1', the definitions of R1, R2, R3, R4, R5, L', A1, A2, w, x and Y are as described in S1.

[0027] In certain embodiments of the invention, S is S1″, [ka] Here, in the above S1″, the definitions of R1, R2, R3, R4, R5, L′, A1, A2, w and Y are as described in S1.

[0028] In certain embodiments of the present invention, in the above S1' or S1'', R1 is hydrogen, a C1-C6 alkyl group or a C1-C6 alkoxy group, and the above C1-C6 alkyl group and C1-C6 alkoxy group are optionally substituted with a C1-C6 alkoxy group (e.g., a methoxy group).

[0029] In a specific embodiment of the present invention, in the above S1' or S1'', R1 is hydrogen, a methyl group, a methoxy group or [ka] is.

[0030] In a specific embodiment of the present invention, in the above S1 and S1′, [ka] The fragment is [ka] is.

[0031] In certain embodiments of the invention, S is -X-S1', where the structure of S1' is as described above, and X is O, NH, or S, preferably O.

[0032] In certain embodiments of the invention, S is -X-S1'', where the structure of S1'' is as described above, and X is O, NH or S, preferably O.

[0033] Preferably, in certain embodiments of the present invention, S is S1a, [ka] Here, in the above S1a, R1 is hydrogen, -OCH3, -OCH2CH3, [ka] , -CH2OH, -C(O)OH, -C(O)OCH3, -Br, -OCH(CH3)2, -O(CH2)2CH(CH3)2, -O(CH2)3CH3, -O(CH2)2OCH3, [ka] , -O(CH2)-phenyl group, -N=S(O)(CH3)2, -CH3, cyclopropyl group, -N(CH3)2, -NHCH3, -NH2, [ka] , -C(CH3)2-OH, [ka] , -NH(CH2)-NH-C(O)CH3, -NH(CH2)-morpholine, -NH-C(O)CH3, -NH-C(O)NHCH3, -NH-C(O)-N(CH3)2, nitro group, -NH-S(O)2CH3, -N=S(O)(CH3)2, hydroxy group, -O-(CH2)2-S(O)2CH3, -F, [ka] , a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexa group, an azetidinyl group, an azacyclopentyl group, a piperidinyl group, a piperazinyl group, an oxetane group, an oxolane group, an oxane group, a thietane group, a thiolane group, a thiane group, an azacyclobutanyloxy group, an azacyclopentyloxy group, a piperidinyloxy group, a piperazinyloxy group, an oxetanyloxy group, an oxolanyloxy group, an oxanyloxy group, a thietanyloxy group, a thianyloxy group, a thiolanyloxy group, [ka] , -OCH2CH2CH3, -OCH2CH2CH2N(CH3)2, -OCH2CH2CH2OH, [ka] , -OCH2CH2NC(O)CH3, -OCH2CH2N(CH3)2, -OCH2CH2OH, [ka] , -SCH3, -N(CH3)2, [ka] Selected from x is 1 or 2, A1 is [ka] Selected from R2 is selected from hydrogen, hydroxy, oxo, cyano, cyclopropyl, 1,1-dimethylcyclopropyl, -C(=CH2)CH3, -C(CH3)(=CH2)CH3, -CH=CH(CH2)2CH3, -CH=CHCH3, -CH=CH-cyclopropyl, -C(O)NH2, -C(O)OCH3, -S(O)2CH3, -OCH3, -CH2NH2, trifluoromethyl, methyl, trifluoromethoxy, or halogen (F, Cl, Br), -NH2, -NHC(O)CH3, -NHCH2CH3 or -NHCH(CH3)2; w is 1, 2 or 3; A2 is [ka] Selected from R 3 are -C(O)NH(CH2)2CH3, -C(O)N(CH3)2, -C(O)NH2, -C(O)NH(CH2)2N(CH3)2, -CH2C(O)NH2, hydrogen, -F, -Cl, -Br, cyano group, -CF3, -CH3, -CH2CH3, -CH=CH2, -CH2CN, -CH(CH3)-NH2, -CH=CH-CN, -C(O)-OH, -C(O)OCH3, -C(O)CH3, -C(CH3)2-C(O)-OCH3, -C(CH3)2-CN, oxo group, hydroxy group, cyclopropyl group, cyclobutyl group, cyclopentyl group, -NH2, -NH-C(O)CH3, -NH-S(O)2CH3, -NH-C(O)OC(CH3)3, [ka] , -S(O)2CH3, -S(O)2NCH3, -S(O)2NH2, -OCH2CH3, -O(CH2)2CH3, -OCF3, [ka] , -OCH2cyclopropyl, -OCH3, -O(CH2)3CH3, -OCH2phenyl group, -O-phenyl group, -(CH2)-OH, -(CH2)2-OH, -(CH2)-OCH3, -(CH2)-OCH2CH3, -CH(OH)-CH2-phenyl group, -CH(OH)-CH2CH3, -CH(OH)-CH2CH2CH3, -CH(OH)-CH2CH2CH2CH3, -CH(OH)-CH(CH3)2, -CH(OH)-phenyl group, -CH(OH)-CN, -CH(OH)-CH2-OH, -CH(OH)-CF3, -CH(OH)-(CH2)2-phenyl group, * -CH(OH)-C≡CH, -CH(NH2)-CH2-C(O)OH, -CH2-NH-S(O)2-CH3, -CH2-NH-(CH2)3CH3, -CH2-NH-CH3, -CH2-N(CH3)2, -CH2-NH-CH2CH3, -CH(CH3)-NH2, -CH2-NH2, -CH2CH2-NH2, -CH2NH-CH2-phenyl group, -CH2N(CH2CH3)2, -CH2NH-cyclopropyl group, -CH2N H-cyclobutyl group, -CH2NH-cyclopentyl group, -CH2NH-pyridyl group, -CH2NH-phenyl group, -CH2NH-(CH2)2-OH, -CH2N(CH3)-(CH2)2-OH, -CH2NH-C H2-CN, -CH2N(CH3)-CH2-CN, -CH2N(CH3)-CH2-CF3, -CH2N(CH3)-CH2-CF2H, -CH2NH-CH2-CF2H, -CH2NH-(CH2)2-OCH3, [ka] , -CH2NH-C(O)-OC(CH3)3, -CH2CH2NH-C(O)-OC(CH3)3, -CH2NH-C(O)-CH2NOH, -CH2NH-C(O)-CH2OCH3, -CH(CH3)NH-C(O)-OC(CH3)3, -CH2NH-C(O)-CH3, [ka] , -CH2NHCH2-C(O)-NH2, -CH2NHCH2-C(O)-(CH3)2, -CH2NHCH2-C(O)-OCH3, -CH2NHCH2-C(O)-NHCH3, -CH2NHCH2-C(O)-NH(CH2)2-OCH3, -CH2NHCH2-C(O)-NHCH2-phenyl group, [ka] , -CH2NHCH2-C(O)-NH-phenyl group, [ka] , -CH2NH-C(O)-CH2NH-phenyl group, [ka] or —CH2NH—C(O)—CH2NH—CH2CF3, Y is 1 or 2; L' is a bond, -(CH2) k - or -O(CH2) k -, wherein k is 1 or 2, or L' is -CH=CH-(CH2) n -, wherein n is 0, 1 or 2.

[0034] In some embodiments, in the above S1a, R2 is selected from hydrogen, a hydroxy group, an oxo group, a cyano group, a cyclopropyl group, 1,1-dimethylcyclopropyl, -C(=CH2)CH3, -C(CH3)(=CH2)CH3, -CH=CH(CH2)2CH3, -CH=CHCH3, -CH=CH-cyclopropyl, -C(O)NH2, -C(O)OCH3, -S(O)2CH3, -OCH3, -CH2NH2, a trifluoromethyl group, a methyl group, a trifluoromethoxy group, and a halogen (F, Cl, Br).

[0035] In a specific embodiment of the present invention, in S1a above, w is 1 or 2.

[0036] In certain embodiments of the invention, in S1a above, R1 is hydrogen, -CH3, -OCH3, -OCH2CH3, -OCH(CH3)2, -O(CH2)2CH(CH3)2 or -O(CH2)3CH3, for example -OCH3.

[0037] In a specific embodiment of the present invention, in the above S1a, A1 is [ka] is.

[0038] In a specific embodiment of the present invention, in the above S1a, A1 is [ka] is.

[0039] In certain embodiments of the present invention, in the above S1a, R2 is hydrogen, halogen, -NH2, a C1-C6 alkyl group or a -C1-C6 haloalkyl group.

[0040] In certain embodiments of the present invention, in S1a above, L' is a bond.

[0041] In a particular embodiment of the present invention, in the above S1a, A2(R3) Y is hydrogen.

[0042] In a specific embodiment of the present invention, in the above S1a, A2 is [ka] is.

[0043] In certain embodiments of the present invention, in S1a above, R3 is hydrogen, -F, -Cl, -Br, -CH2-NH-(CH2)3CH3, -CH2-NH-CH3, -CH2-N(CH3)2 or -CH2-NH-CH2CH3.

[0044] In certain embodiments of the present invention, in S1a above, R3 is hydrogen, Cl, -CH2NHCH3 or -CH2N(CH3)2.

[0045] In a specific embodiment of the present invention, in the above S1a, A1 is [ka] and L' is a bond, and A2(R3) Y is hydrogen.

[0046] In a specific embodiment of the present invention, in the above S1a, A1 is [ka] where L' is a bond and A2 is [ka] and R3 is hydrogen, -F, -Cl, -Br, -CH2-NH-(CH2)3CH3, -CH2-NH-CH3, -CH2-N(CH3)2, or -CH2-NH-CH2CH3.

[0047] In certain embodiments of the invention, S is S1a′, [ka] Here, in the above S1a', the definitions of R1, R2, R3, L', A1, A2, w, x and Y are as described in S1 or S1a.

[0048] In a particular embodiment of the invention, S is S1a″, [ka] Here, in the above S1a'', the definitions of R1, R2, R3, L', A1, A2, w and Y are as described in S1 or S1a.

[0049] In certain embodiments of the present invention, in the above S1a' and S1a'', R1 is hydrogen, a C1-C6 alkyl group or a C1-C6 alkoxy group, and the above C1-C6 alkyl group and C1-C6 alkoxy group are optionally substituted with a C1-C6 alkoxy group (e.g., a methoxy group).

[0050] In a specific embodiment of the present invention, in the above S1a′ and S1a″, R1 is hydrogen, a methyl group, a methoxy group, or [ka] is.

[0051] In a specific embodiment of the present invention, in the above S1a, S1a', and S1a'', [ka] The fragment is [ka] is.

[0052] In certain embodiments of the invention, S is -X-S1a', where the structure of S1a' is as described above, and X is O, NH or S, preferably O.

[0053] In certain embodiments of the invention, S is -X-S1a'', where the structure of S1a'' is as described above, and X is O, NH or S, preferably O.

[0054] More preferably, in certain embodiments of the present invention, S1 is a specific compound of Example 1 to Example 458 of WO2018172250A1 (the entire text of which is incorporated herein by reference).

[0055] Preferably, in certain embodiments of the present invention, S is S2, [ka] Here, in the above S2, R1 is hydrogen, halogen, -OH, -CN, -NO2, a C1-C6 alkylmercapto group, or -NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R1 is a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkoxy group, a C3-C6 heterocycloalkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, a C4-C8 cycloalkenyl group, a 4- to 7-membered heterocycloalkyl group, a 5- to 10-membered heterocycloalkenyl group, a spiroheterocycloalkyl group, a fused heterocycloalkyl group, a bridged heterocycloalkyl group, a phenyl group, a heteroaryl group, a C1-C6 haloalkyl group, -COOH, -COOR c and R c is a -C1-C6 alkyl group, a C3-C6 alkenyl group, a C3-C6 alkynyl group, a C3-C8 cycloalkyl group or a -C4-C8 cycloalkenyl group, R1 is -NS(O)(R d )(R e ) and the above R d and R e are each independently a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, or a C4-C8 cycloalkenyl group, R1 is -NHC(O)-(C1-C6 alkyl), -NHC(O)-NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R1 is -NH-(CH2) k -NH-C(O)-(C1-C6 alkyl), wherein k is 1 or 2; R1 is -NH-(CH2) i -R f wherein i is 0, 1 or 2, and R f is a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, or a C1-C6 alkylsulfonyl group, The C1-C6 alkyl group, C1-C6 alkoxy group, 4- to 7-membered heterocycloalkyl group, and heteroaryl group may optionally be selected from the group consisting of halogen, -OH, oxo, -CN, -NO2, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C8 cycloalkyl group, 4- to 7-membered heterocycloalkyl group, C1-C6 alkoxy group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, C1-C6 alkylsulfonyl group, phenyl group, benzyl group, heteroaryl group, -(CH2)-heteroaryl group, -NHC(O)(C1-C6 alkyl), C3-C8 cycloalkoxy group, phenoxy group, heteroaryloxy group, and -NR a R b and R a and R b are each independently selected from hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R1 is -O-(CH2) z -phenyl group, -O-(CH2) z -(4-7 membered heterocycloalkyl), -O-(CH2) z -heteroaryl group, wherein z is 0, 1 or 2, and the phenyl group, heterocycloalkyl group and heteroaryl group are optionally substituted with a group selected from -OH, heterocycloalkyl group or heterocycloalkenyl group, and can be substituted with a methyl group or an oxo group; Or R1 is [ka] wherein L2a is C(O), L2b is a bond or a C1-C6 alkylene group, and X2 is [ka] and Rx2 is [ka] and Or R1 is [ka] and or two adjacent R1's together with the carbon atoms connected thereto form a 5- to 7-membered cycloalkyl group or a 5- to 7-membered heterocycloalkyl group, and x is 1, 2, 3, or 4 (e.g., x is 1, 2, or 3); A1 is C4-C 12 a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; R2 is hydrogen, -OH, oxo, halogen, -CN, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C2-C6 alkenyl group, a -C2-C6 alkynyl group, a -C3-C8 cycloalkyl group, a -C3-C8 cycloalkoxy group, a -C3-C8 halocycloalkoxy group, a -C4-C8 cycloalkenyl group, a 4- to 7-membered heterocycloalkyl group, -O-CH2-4- to 7-membered heterocycloalkyl group, a 5- to 10-membered heterocycloalkenyl group, a spiroheterocycloalkyl group, a fused heterocycloalkyl group, a bridged heterocycloalkyl group, a phenyl group, a heteroaryl group, a -C1-C6 haloalkyl group, a -C1-C6 haloalkoxy group, or a -C1-C6 alkylsulfonyl group; R2 is -NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R2 is -C(O)NR a R b and the above R a and R bare each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R2 is -C(O)OR g and the above R g is hydrogen or a C1-C6 alkyl group, R2 is -OR h and the above R h is a C1-C6 alkyl group, R2 is -(CH2)NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; and w is 1, 2, 3, or 4 (e.g., the above w is 1 or 2); Above A2(R3) Y is hydrogen, Or A2 is C4-C 12 a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, and R3 is hydrogen, halogen, -OH, oxo, -CN, -NO2, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, a C4-C8 cycloalkenyl group, a C2-C8 cycloalkynyl group, a 4- to 7-membered heterocycloalkyl group, a 5- to 10-membered heterocycloalkenyl group, a phenyl group, a heteroaryl group, or a C1-C6 haloalkyl group; The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl, and heterocycloalkenyl groups may optionally be selected from the group consisting of halogen, —OH, oxo, —CN, —C1-C6 alkyl, —C1-C6 alkoxy, —C1-C6 haloalkyl, phenyl, heteroaryl, or —C(O)NR i R j and R i and R jare each independently hydrogen or a C1-C6 alkyl group; or the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups are optionally -NR k R l The above R is replaced by k and R l are each independently hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, a C1-C6 alkylsulfonyl group, a phenyl group, a heteroaryl group, -CH2-C(O)-R m , -C(O)R p or a 4- to 7-membered heterocycloalkyl group, wherein the alkyl group, alkynyl group, alkenyl group, cycloalkyl group, phenyl group, heteroaryl group, and heterocycloalkyl group are each independently optionally substituted with one, two, or three groups selected from a C1-C6 haloalkyl group, —OH, an oxo group, a phenyl group, —CN, a C1-C6 alkoxy group, or a heteroaryl group, and the heteroaryl group is optionally substituted with a methyl group, and the R m is a bicyclic heteroaryl group, a C1-C6 alkoxy group or -NR n R o and the above R n and R o are each independently hydrogen, a C1-C6 alkyl group, or a phenyl group, the alkyl group being optionally substituted with a C1-C6 alkoxy group or a phenyl group, or -NR n R o is a 4- to 7-membered azacycloalkyl group, which is linked to other parts of the molecule via a N atom and further contains one or more heteroatoms selected from N and O, and R p is selected from a C1-C6 alkoxy group, a C1-C6 alkyl group optionally substituted with 1, 2 or 3 groups selected from —OH or a C1-C6 alkoxy group, a monocyclic or bicyclic heteroaryl group, a 4- to 7-membered heterocycloalkyl group, or R p is -CH2-NRq R r and the above R q and R r are each independently selected from hydrogen, a phenyl group, or a C1-C6 alkyl group optionally substituted with F; or the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups are optionally -NR s R t The above is substituted with -NR s R t is a 4- to 7-membered azacycloalkyl group linked to another part of the molecule through a nitrogen atom or a 6- to 10-membered azaspiroheterocycloalkyl group linked to another part of the molecule through a nitrogen atom, and further contains at most two heteroatoms selected from N or O, and optionally contains -OH, oxo group, C1-C6 alkyl group, C1-C6 hydroxyalkyl group, -C(O)OR z and R z is a C1-C6 alkyl group, halogen, -N(C1-C6 alkyl)2, -CH2N(C1-C6 alkyl)2, -C(O)NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; or R3 is C(O)R v , -C(O)NH2, -C(O)NHR v , -C(O)NR v R w , -C(O)OR v and the above R v and R w are each independently a hydrogen atom, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a phenyl group, or -(CH2)2NR x R y and the above R x and R yare each independently hydrogen, a C1-C4 alkyl group, or —(CH2)2NH(CH3)2; Or R3 is -NH2, -NHR z , -NR z R za , -NHC(O)R z , -NHC(O)OR z , -NHS(O)2R z , a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, a spiro heterocycloalkyl group, a fused heterocycloalkyl group, or a bridged heterocycloalkyl group; z and R za are each independently a C1-C4 alkyl group, a C1-C4 haloalkyl group, or a phenyl group; Or R3 is a C1-C6 alkoxy group, a C1-C6 haloalkoxy group, -O(CH2) s -C3-C8 cycloalkyl group, -O(CH2) s -phenyl group, -O(CH2) s -heterocycloalkyl group, -O(CH2) s -heteroaryl group, where s is 0, 1, 2 or 3; Or R3 is -S(O)2R z , -S(O)2NH2, -S(O)2NHR z , -S(O)NR z R za and the above R z and R za are each independently a C1-C4 alkyl group, a C1-C4 haloalkyl group, or a phenyl group; Y is 0, 1, 2, 3, 4, or 5 (e.g., Y is 0, 1, 2, or 3); L' is a bond, -(CH2) k -, -O(CH2) k -, -(CH2) k -O- or -O-(CH2) k -O- (for example, L' above is a bond, -(CH2) k - or -O(CH2) k -), wherein k is 0, 1, 2 or 3, or L' is -CH=CH-(CH) nwherein n is 0, 1 or 2; R4 and R5 each independently represent a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, or a C3-C6 cycloalkoxy group, and the alkyl group, alkoxy group, cycloalkyl group, and cycloalkoxy group are optionally substituted with a cyano group, a hydroxy group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, or a halogen; T and V are both N, or T is C and V is N, or T is N and V is C.

[0056] Preferably, in a specific embodiment of the present invention, in the above S2, R4 and R5 are each independently a methyl group.

[0057] In some embodiments, in the definition of each group of S2, a and R b appears at any position, each independently is hydrogen or a C1-C6 alkyl group.

[0058] In a specific embodiment of the present invention, T and V are both N in S2 above.

[0059] In a specific embodiment of the present invention, T is C and V is N in S2 above.

[0060] In a specific embodiment of the present invention, T is N and V is C in S2 above.

[0061] In a specific embodiment of the present invention, in the above S2, R5 is a C1-C6 alkyl group, for example a methyl group.

[0062] In a specific embodiment of the present invention, in the above S2, R4 is a C1-C6 alkyl group, for example a methyl group.

[0063] In certain embodiments of the present invention, in the above S2, R1 is hydrogen or a C1-C6 alkoxy group.

[0064] In certain embodiments of the present invention, in the above S2, A1 is an aryl group or a heteroaryl group.

[0065] In a specific embodiment of the present invention, in the above S2, A1 is an aryl group, for example a phenyl group.

[0066] In certain embodiments of the present invention, in the above S2, A1 is a heteroaryl group, for example a thienyl group.

[0067] In certain embodiments of the present invention, in the above S2, R2 is hydrogen, halogen, a C1-C6 alkyl group, or a -C1-C6 haloalkyl group.

[0068] In certain embodiments of the present invention, in S2 above, L' is a bond.

[0069] In a specific embodiment of the present invention, in the above S2, A2(R3) Y is hydrogen.

[0070] In certain embodiments of the present invention, in the above S2, A2 is an aryl group, for example a phenyl group.

[0071] In certain embodiments of the present invention, in S2 above, R3 is hydrogen, halogen or a C1-C6 alkyl group, and the alkyl group is optionally -NR k R l The above R is replaced by k and R l are each independently hydrogen or a C1-C6 alkyl group. In a specific embodiment of the present invention, in the above S7, R3 is hydrogen, F, Cl, a methyl group, or an ethyl group, and the methyl group and ethyl group are -NR k R l The above R is replaced by k is a methyl group or an ethyl group, and R l is hydrogen, a methyl group, or an ethyl group.

[0072] In certain embodiments of the present invention, in the above S2, R3 is hydrogen, Cl, -CH2NHCH3 or -CH2N(CH3)2.

[0073] In a specific embodiment of the present invention, in the above S2, A1 is an aryl group, L' is a bond, A2(R3) Y is hydrogen.

[0074] In certain embodiments of the present invention, in the above S2, A1 is a heteroaryl group, L' is a bond, A2 is an aryl group, and R3 is hydrogen, halogen, or a C1-C6 alkyl group, wherein the alkyl group is optionally -NR k R l The above R is replaced by k and R l are each independently hydrogen or a C1-C6 alkyl group.

[0075] In certain embodiments of the invention, S is S2′, [ka] Here, in S2' above, the definitions of T, V, R1, R2, R3, R4, R5, L', A1, A2, w, x and Y are as described in S2.

[0076] In certain embodiments of the invention, S is S2″, [ka] Here, in the above S2″, the definitions of R2, R3, R4, R5, L′, A1, A2, w and Y are as described in S2.

[0077] In certain embodiments of the present invention, in the above S2, S2', and S2'', R1 is hydrogen, a C1-C6 alkyl group, or a C1-C6 alkoxy group, and the above C1-C6 alkyl group and C1-C6 alkoxy group are optionally substituted with a C1-C6 alkoxy group (e.g., a methoxy group).

[0078] In a specific embodiment of the present invention, in the above S2, S2', and S2'', R1 is hydrogen, a methyl group, a methoxy group, or [ka] is.

[0079] In a specific embodiment of the present invention, in the above S2 and S2', [ka] The fragment is [ka] is.

[0080] In certain embodiments of the invention, S is -X-S2', where the structure of S2' is as described above, and X is O, NH or S, preferably O.

[0081] In certain embodiments of the invention, S is -X-S2'' where the structure of S2'' is as described above and X is O, NH or S, preferably O.

[0082] Preferably, in certain embodiments of the invention, S is S2a, [ka] Here, in the above S2a, T and V are both N, or T is C and V is N, or T is N and V is C; R1 is hydrogen, -OCH3, -OCH2CH3, [ka] , -CH2OH, -C(O)OH, -C(O)OCH3, -Br, -OCH(CH3)2, -O(CH2)2CH(CH3)2, -O(CH2)3CH3, -O(CH2)2OCH3, [ka] , -O(CH2) z -phenyl group, -N=S(O)(CH3)2, -CH3, cyclopropyl group, -N(CH3)2, -NHCH3, -NH2, [ka] , -C(CH3)2-OH, [ka] , -NH(CH2)-NH-C(O)CH3, -NH(CH2)-morpholine, -NH-C(O)CH3, -NH-C(O)NHCH3, -NH-C(O)-N(CH3)2, nitro group, -NH-S(O)2CH3, -N=S(O)(CH3)2, hydroxy group, -O-(CH2)2-S(O)2CH3, -F, [ka] , a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexa group, an azetidinyl group, an azacyclopentyl group, a piperidinyl group, a piperazinyl group, an oxetane group, an oxolane group, an oxane group, a thietane group, a thiolane group, a thiane group, an azacyclobutanyloxy group, an azacyclopentyloxy group, a piperidinyloxy group, a piperazinyloxy group, an oxetanyloxy group, an oxolanyloxy group, an oxanyloxy group, a thietanyloxy group, a thiolanyloxy group, a thianyloxy group, [ka] , -OCH2CH2CH3, -OCH2CH2CH2N(CH3)2, -OCH2CH2CH2OH, [ka] , -OCH2CH2NC(O)CH3, -OCH2CH2N(CH3)2, -OCH2CH2OH, [ka] , -SCH3, -N(CH3)2, [ka] Selected from z is 1 or 2; x is 1 or 2, A1 is [ka] Selected from R2 is selected from hydrogen, a hydroxy group, an oxo group, a cyano group, a cyclopropyl group, a 1,1-dimethylcyclopropyl group, -C(=CH2)CH3, -C(CH3)(=CH2)CH3, -CH=CH(CH2)2CH3, -CH=CHCH3, -CH=CH-cyclopropyl group, -C(O)NH2, a trifluoromethyl group, a methyl group, a trifluoromethoxy group, -C(O)OCH3, -S(O)2CH3, -OCH3, -CH2NH2 or a halogen (F, Cl, Br); w is 1, 2 or 3; A2 is [ka] Selected from R 3 are -C(O)NH(CH2)2CH3, -C(O)N(CH3)2, -C(O)NH2, -C(O)NH(CH2)2N(CH3)2, -CH2C(O)NH2, hydrogen, -F, -Cl, -Br, cyano group, -CF3, -CH3, -CH2CH3, -CH=CH2, -CH2CN, -CH(CH3)-NH2, -CH=CH-CN, -C(O)-OH, -C(O)OCH3, -C(O)CH3, -C(CH3)2-C(O)-OCH3, -C(CH3)2-CN, oxo group, hydroxy group, cyclopropyl group, cyclobutyl group, cyclopentyl group, -NH2, -NH-C(O)CH3, -NH-S(O)2CH3, -NH-C(O)OC(CH3)3, [ka] , -S(O)2CH3, -S(O)2NCH3, -S(O)2NH2, -OCH2CH3, -O(CH2)2CH3, -OCF3, [ka] , -OCH2 cyclopropyl group, -OCH3, -O(CH2)3CH3, -OCH2 phenyl group, -O-phenyl group, -(CH2)-OH, -(CH2)2-OH, -(CH2)-OCH3, -(CH2)-OCH2CH3, -CH(OH)-CH2-phenyl group, -CH(OH)-CH2CH3, -CH(OH)-CH2CH2CH3, -CH(OH)-CH2CH2CH2CH3, -CH(OH)-CH(CH3)2, -CH(OH)-phenyl group, -CH(OH)-CN, -CH(OH)-CH2-OH, -CH(OH)-CF3, -CH(OH)-(CH2)2-phenyl group, * -CH(OH)-C≡CH, -CH(NH2)-CH2-C(O)OH, -CH2-NH-S(O)2-CH3, -CH2-NH-(CH2)3CH3, -CH2-NH-CH3, -CH2-N(CH3)2, -CH2-NH-CH2CH3, -CH(CH3)-NH2, -CH2-NH2, -CH2CH2-NH2, -CH2NH-CH2-phenyl group, -CH2N(CH2CH3)2, -CH2NH-cyclopropyl group, -CH2N H-cyclobutyl group, -CH2NH-cyclopentyl group, -CH2NH-pyridyl group, -CH2NH-phenyl group, -CH2NH-(CH2)2-OH, -CH2N(CH3)-(CH2)2-OH, -CH2NH-C H2-CN, -CH2N(CH3)-CH2-CN, -CH2N(CH3)-CH2-CF3, -CH2N(CH3)-CH2-CF2H, -CH2NH-CH2-CF2H, -CH2NH-(CH2)2-OCH3, [ka] , -CH2NH-C(O)-OC(CH3)3, -CH2CH2NH-C(O)-OC(CH3)3, -CH2NH-C(O)-CH2NOH, -CH2NH-C(O)-CH2OCH3, -CH(CH3)NH-C(O)-OC(CH3)3, -CH2NH-C(O)-CH3, [ka] , -CH2NHCH2-C(O)-NH2, -CH2NHCH2-C(O)-(CH3)2, -CH2NHCH2-C(O)-OCH3, -CH2NHCH2-C(O)-NHCH3, -CH2NHCH2-C(O)-NH(CH2)2-OCH3, -CH2NHCH2-C(O)-NHCH2-phenyl group, [ka] , -CH2NHCH2-C(O)-NH-phenyl group, [ka] , -CH2NH-C(O)-CH2NH-phenyl group, [ka] or —CH2NH—C(O)—CH2NH—CH2CF3, Y is 1 or 2; L' is a bond, -(CH2) k - or -O(CH2) k -, wherein k is 1 or 2, or L' is -CH=CH-(CH2) n and n is 0 or 1.

[0083] More preferably, in certain embodiments of the present invention, S2 is a specific compound of Example 1 to Example 100 of WO2019201848A1 (the entire text of which is incorporated herein by reference).

[0084] In a specific embodiment of the present invention, in S2a above, w is 1 or 2.

[0085] In a specific embodiment of the present invention, in the above S2a, R1 is hydrogen, a methyl group, -OCH3, -OCH2CH3, -OCH(CH3)2, -O(CH2)2CH(CH3)2 or -O(CH2)3CH3, for example -OCH3.

[0086] In a specific embodiment of the present invention, in S2a above, A1 is [ka] is.

[0087] In a specific embodiment of the present invention, in S2a above, A1 is [ka] is.

[0088] In certain embodiments of the present invention, in the above S2a, R2 is hydrogen, halogen, -NH2, a C1-C6 alkyl group or a -C1-C6 haloalkyl group.

[0089] In certain embodiments of the present invention, in S2a above, L' is a bond.

[0090] In a specific embodiment of the present invention, in the above S2a, A2(R3) Y is hydrogen.

[0091] In a specific embodiment of the present invention, in the above S2a, A2 is [ka] is.

[0092] In certain embodiments of the present invention, in S2a above, R3 is hydrogen, -F, -Cl, -Br, -CH2-NH-(CH2)3CH3, -CH2-NH-CH3, -CH2-N(CH3)2 or -CH2-NH-CH2CH3.

[0093] In certain embodiments of the present invention, in S2a above, R3 is hydrogen, Cl, -CH2NHCH3 or -CH2N(CH3)2.

[0094] In a specific embodiment of the present invention, in S2a above, A1 is [ka] and L' is a bond, and A2(R3) Y is hydrogen.

[0095] In a specific embodiment of the present invention, in S2a above, A1 is [ka] where L' is a bond and A2 is [ka] and R3 is hydrogen, -F, -Cl, -Br, -CH2-NH-(CH2)3CH3, -CH2-NH-CH3, -CH2-N(CH3)2, or -CH2-NH-CH2CH3.

[0096] In certain embodiments of the invention, S is S2a′, [ka] Here, in the above S2a', the definitions of T, V, R1, R2, R3, L', A1, A2, w, x and Y are as described in S2 or S2a.

[0097] In certain embodiments of the invention, S is S2a″, [ka] Here, in the above S2a″, the definitions of T, V, R2, R3, L′, A1, A2, w and Y are as described in S2 or S2a.

[0098] In certain embodiments of the present invention, in the above S2a' and S2a'', R1 is hydrogen, a C1-C6 alkyl group or a C1-C6 alkoxy group, and the above C1-C6 alkyl group and C1-C6 alkoxy group are optionally substituted with a C1-C6 alkoxy group (e.g., a methoxy group).

[0099] In a specific embodiment of the present invention, in the above S2a′ and S2a″, R1 is hydrogen, a methyl group, a methoxy group, or [ka] is.

[0100] In a specific embodiment of the present invention, in the above S2a, S2a', and S2a'', [ka] The fragment is [ka] is.

[0101] In certain embodiments of the invention, S is -X-S2a', where the structure of S2a' is as described above, and X is O, NH or S, preferably O.

[0102] In certain embodiments of the invention, S is -X-S2a'' wherein the structure of S2a'' is as described above and X is O, NH or S, preferably O.

[0103] Preferably, in certain embodiments of the present invention, S is S3, [ka] Here, in the above S3, Q 1 and Q 2 are each independently CH or N; Q 3 , Q 4and Q 7 are each independently C or N, and the Q 3 and Q 4 At least one of the above is C, and 3 , Q 4 and Q 7 is not all N, Q 5 is CH, N, NH, O or S, Q 6 is CH, N, NH, N(C1-C6 alkyl), N(C1-C6 heteroalkyl), N(3- to 7-membered cycloalkyl), N(3- to 7-membered heterocycle), O, or S; The above Q 1 , Q 2 , Q 3 , Q 4 , Q 5 , Q 6 and Q 7 at least one of is N, NH, O or S; R 1 is hydrogen, C1-C6 alkyl group, C1-C6 alkoxy group, halogen, -NHR 1a , -OR 1a , a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, or -CN, wherein the C1-C6 alkyl group, C1-C6 alkoxy group, C3-C6 cycloalkyl group, and C3-C6 cycloalkoxy group are optionally selected from halogen, -NHR 1a -OR 1a and R 1a is hydrogen, a C1-C6 alkyl group, a 3- to 6-membered heterocycle, or a C1-C6 haloalkyl group, L 2 is a bond, -C(O)-, -C(O)O-, -C(O)NH(CH2) o -, -S(O)2-, -S(O)-, -S(=O)(=NH)-, -S(=O)[=N(C1-C6 alkyl)]-, -N(C1-C6 alkyl)-, -C(O)(CH2) p -, -(CH2) p - or O, wherein o is 0, 1 or 2, and p is an integer of 1 to 6; R 2is hydrogen, halogen, -CN, -NO2, C1-C6 alkylmercapto group, C2-C6 alkynyl group, C1-C6 alkyl group, C2-C6 alkenyl group, -NR 2b R 2c , -OR 2a , a 3- to 14-membered cycloalkyl group, a 3- to 14-membered cycloalkenyl group, a 3- to 14-membered heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group, wherein the C1-C6 alkyl group, C2-C6 alkenyl group, 3- to 14-membered cycloalkyl group, 3- to 14-membered cycloalkenyl group, 3- to 14-membered heterocycloalkyl group, 6- to 10-membered aryl group, and 5- to 10-membered heteroaryl group are each independently optionally selected from C1-C6 alkyl groups, C1-C6 haloalkyl groups, -OH, -OR 2a , oxo group, halogen, -C(O)R 2a , -C(O)OR 2a , -C(O)NR 2b R 2c , -CN, -NR 2b R 2c , a 3- to 6-membered cycloalkyl group, a 3- to 7-membered heterocycloalkyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group; 2a is hydrogen, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a 3- to 7-membered heterocycloalkyl group, or -(CH2) r OCH3, wherein r is 1, 2, or 3; Above R 2b is hydrogen or a C1-C6 alkyl group, Above R 2c is hydrogen or a C1-C6 alkyl group, R 2 is -NHC(O)-(C1-C6 alkyl), -NHC(O)-NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group (e.g., the R a and R b are each independently hydrogen or a C1-C6 alkyl group; R 2 is -NH-(CH2) k -NH-C(O)-(C1-C6 alkyl), wherein k is 1 or 2; R 2 is -NH-(CH2) i -R f wherein i is 0, 1 or 2, and R f is a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, or a C1-C6 alkylsulfonyl group, R 3 and R 4 are each independently hydrogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, or a C3-C6 cycloalkoxy group, and the R 3 and R 4 At least one of the above R 3 and R 4 form a 3- to 6-membered cycloalkyl group together with the atoms connected thereto, and the alkyl group, alkoxy group, cycloalkyl group, and cycloalkoxy group are optionally substituted with a cyano group, a hydroxy group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, or a halogen; A is an optionally substituted (e.g., optionally one or more R2 substitutions, where R2 is as defined in S1) 6-membered aryl group or an optionally substituted (e.g., optionally one or more R2 substitutions, where R2 is as defined in S1) 5-6 membered heteroaryl group.

[0104] Preferably, in certain embodiments of the invention, S is S3a, [ka] Here, in S3a above, Q 1 and Q 2 are each independently CH or N; Q 3 and Q 4 are each independently C or N, and the Q 3 and Q4 at least one of is C, Q 6 is CH, N, NH, O or S, Q 5 is CH, N, NH, O or S, The above Q 1 , Q 2 , Q 3 , Q 4 , Q 5 and Q 6 at least one of is N, NH, O or S; R 1 is hydrogen, C1-C6 alkyl group, halogen, -OR 1a , a cyclopropyl group, or —CN, and 1a is hydrogen or a C1-C6 alkyl group, L 2 is a bond, -C(O)-, -C(O)O-, -C(O)NH(CH2) o -, -S(O)2-, -C(O)(CH2) p -, -(CH2) p - or O, wherein o is 0, 1 or 2, and p is an integer of 1 to 6; R 2 is hydrogen, -(CH2) q CH3, a 3- to 14-membered cycloalkyl group, a 3- to 14-membered cycloalkenyl group, a 3- to 14-membered heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group, wherein q is an integer of 1 to 5, and the 3- to 14-membered cycloalkyl group, the 3- to 14-membered cycloalkenyl group, the 3- to 14-membered heterocycloalkyl group, the 6- to 10-membered aryl group, and the 5- to 10-membered heteroaryl group each independently optionally represent a C1-C6 alkyl group, —OH, halogen, —C(O)R 2a , -C(O)NR 2b R 2c and R 2a is a C1-C6 alkyl group or -(CH2) r OCH3, wherein r is 1, 2 or 3, and R 2b is hydrogen or a C1-C6 alkyl group, and the R 2c is hydrogen or a C1-C6 alkyl group, R 3 and R 4 are each independently hydrogen or a C1-C6 alkyl group, and the R 3 and R 4 At least one of the above R 3 and R 4 form a 3- to 6-membered cycloalkyl group together with the atoms to which they are connected; A is an optionally substituted (e.g., optionally one or more R2 substitutions, where R2 is as defined in S1) phenyl group or an optionally substituted (e.g., optionally one or more R2 substitutions, where R2 is as defined in S1) 5-6 membered heteroaryl group.

[0105] More preferably, in certain embodiments of the present invention, S3 is a specific compound of Example 1 to Example 103 of WO2020180768A1 (the entire text of which is incorporated herein by reference).

[0106] Preferably, in certain embodiments of the present invention, S is S4, [ka] Here, in the above S4, Q 1 is CH or N, Q 4 is CH, C or N, Each Q 2 are each independently CR 1 or N, and the above Q 2 One of them is N and the other is Q 2 is CR 1 and Each Q 3 and Q 5 The molecules are independently C(R QC )2, NR QN , C(O), O, S or SO2, and the R QC are each independently hydrogen, F, Cl, Br, or a 6- to 10-membered aryl group, and the RQN are each independently hydrogen, a C1-C6 alkyl group, or a 6- to 10-membered aryl group; The above Q 1 , Q 2 , Q 3 , Q 4 and Q 5 At least one of N, NR QN , O or SO2, m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; and if m is 0, then n is not 0, R 1 represents hydrogen, C1-C6 alkyl groups, halogens, -C(O)NHR 1a , -NHR 1a , -OR 1a , cyclopropyl, azetidine or -CN, wherein the C1-C6 alkyl group and azetidine are optionally selected from halogen, R 1a , -NHR 1a -OR 1a and R 1a is hydrogen, a C1-C6 alkyl group, a cyclopropyl group, a 3- to 6-membered heterocycle, or a C1-C6 haloalkyl group, L 2 is a bond, -C(O)-, -C(O)O-, -C(O)NH(CH2) o -, -S(O)2-, -S(O)-, -S(=O)(=NH)-, -S(=O)[=N(C1-C6 alkyl)]-, -N(C1-C6 alkyl)-, -C(O)(CH2) p -, -(CH2) p - or O, wherein o is 0, 1 or 2, and p is an integer of 1 to 6; R 2 represents hydrogen, C1-C6 alkyl group, -NR 2b R 2c , -OR 2a, a 3- to 14-membered cycloalkyl group, a 3- to 14-membered cycloalkenyl group, a 3- to 14-membered heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group, wherein the C1-C6 alkyl group, the 3- to 14-membered cycloalkyl group, the 3- to 14-membered cycloalkenyl group, the 3- to 14-membered heterocycloalkyl group, the 6- to 10-membered aryl group, and the 5- to 10-membered heteroaryl group are each independently optionally selected from a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C1-C6 hydroxyalkyl group, a C1-C6 methoxyalkyl group, -OH, -OR 2a , oxo group, halogen, =N, -C(O)R 2a , -C(O)OR 2a , -C(O)NR 2b R 2c , -S(O)2R 2a , -CN, -NR 2b R 2c , a 3- to 6-membered cycloalkyl group, a 3- to 7-membered heterocycloalkyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group; 2a is hydrogen, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a 3- to 7-membered heterocycloalkyl group, or -(CH2) r OCH3, wherein r is 1, 2, or 3; Above R 2b is hydrogen or a C1-C6 alkyl group, Above R 2c is hydrogen or a C1-C6 alkyl group, R 3 and R 4 are each independently hydrogen, a C1-C6 alkyl group optionally substituted with halogen or —OH, and 3 and R 4 At least one of the R 3 and R 4 form a 3- to 6-membered cycloalkyl group together with the atoms to which they are connected; A is an optionally substituted (e.g., optionally one or more R2 substitutions, where R2 is as defined in S1) 6-membered aryl group or an optionally substituted (e.g., optionally one or more R2 substitutions, where R2 is as defined in S1) 5-6 membered heteroaryl group; As a condition, [ka] but [ka] If R 1 is not hydrogen.

[0107] Preferably, in certain embodiments of the invention, S is S4a, [ka] Here, in S4a above, Q 1 is CH or N, Q 4 is CH, C or N, Each Q 2 are each independently CR 1 or N, Each Q 3 and Q 5 The molecules are independently C(R QC )2, NR QN , C(O), O, S or SO2, and the R QC are each independently hydrogen, F, Cl, Br, or a 6- to 10-membered aryl group, and the R QN are each independently hydrogen, a C1-C6 alkyl group, or a 6- to 10-membered aryl group; The above Q 1 , Q 2 , Q 3 , Q 4 and Q 5 At least one of N, NR QN , O or SO2, R 1is hydrogen, a C1-C6 alkyl group, a halogen, a cyclopropyl group, a cyano group, or -OR 1a and R 1a is hydrogen or a C1-C6 alkyl group, L 2 is a bond, -C(O)-, -C(O)O-, -C(O)NH(CH2) o -, -S(O)2-, -C(O)(CH2) p -, -(CH2) p - or O, wherein o is 0, 1 or 2, and p is an integer of 1 to 6; R 2 is hydrogen, -(CH2) q CH3, a 3- to 14-membered cycloalkyl group, a 3- to 14-membered cycloalkenyl group, a 3- to 14-membered heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group, wherein q is a multiple of 1 to 5, and the 3- to 14-membered cycloalkyl group, the 3- to 14-membered cycloalkenyl group, the 3- to 14-membered heterocycloalkyl group, the 6- to 10-membered aryl group, and the 5- to 10-membered heteroaryl group each independently optionally represent a C1-C6 alkyl group, a hydroxy group, a halogen, or -C(O)R 2a or -C(O)NR 2b R 2c and R 2a is a C1-C6 alkyl group or -(CH2) r OCH3, wherein r is 1, 2 or 3, and R 2b and R 2c are each independently hydrogen or a C1-C6 alkyl group; R 3 and R 4 are each independently hydrogen or a C1-C6 alkyl group, and the R 3 and R 4 At least one of the R 3 and R 4 form a 3- to 6-membered cycloalkyl group together with the atoms to which they are connected; A is an optionally substituted (e.g., optionally one or more R2 substitutions, where R2 is as defined in S1) 6-membered aryl group or an optionally substituted (e.g., optionally one or more R2 substitutions, where R2 is as defined in S1) 5-6 membered heteroaryl group.

[0108] Preferably, in certain embodiments of the present invention, in S4a above, R 3 and R 4 are each independently hydrogen or a methyl group, and the R 3 and R 4 At least one of is hydrogen.

[0109] More preferably, in certain embodiments of the present invention, S4 is a specific compound of Example 1 to Example 540 of WO2020180770A1 (the entire text of which is incorporated herein by reference).

[0110] Preferably, in certain embodiments of the present invention, S is S5, [ka] Here, in the above S5, Above R 1 is hydrogen or R a1 and R a1 represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C1-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C4-C 10 Cycloalkenyl group, 3-10 membered heterocycloalkyl group, C6-C 10 an aryl group or a 5- to 10-membered heteroaryl group, and the C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C1-C6 alkynyl group, C3-C 10 Cycloalkyl groups, C4-C 10 Cycloalkenyl group, 3-10 membered heterocycloalkyl group, C6-C 10The aryl group and the 5- to 10-membered heteroaryl group may optionally be substituted with one or more identical or different R b1 and / or R c1 is replaced by Each R b1 are independently -OR c1 , -NR c1 R c1 , halogen, -CN, -C(O)R c1 , -C(O)OR c1 , -C(O)NR c1 R c1 , -S(O)2R c1 , -S(O)NR c1 R c1 , -NHC(O)R c1 , -N(C1-C4 alkyl)C(O)R c1 , -NHC(O)OR c1 or -N(C1-C4 alkyl)C(O)OR c1 and Each R c1 are each independently hydrogen, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C4-C 10 Cycloalkenyl group, 3-10 membered heterocycloalkyl group, C6-C 10 an aryl group or a 5- to 10-membered heteroaryl group, and the C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C 10 Cycloalkyl groups, C4-C 10 Cycloalkenyl group, 3-10 membered heterocycloalkyl group, C6-C 10 The aryl group and the 5- to 10-membered heteroaryl group each independently optionally contain one or more identical or different R d1 and / or R e1 is replaced by Each R d1 are independently -OR e1 , -NR e1 R e1 , halogen, -CN, -C(O)R e1 , -C(O)OR e1 , -C(O)NRe1 R e1 , -S(O)2R e1 , -S(O)NR e1 R e1 , -NHC(O)R e1 , -N(C1-C4 alkyl)C(O)R e1 , -NHC(O)OR e1 or -N(C1-C4 alkyl)C(O)OR e1 and Each R e1 are each independently hydrogen, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C4-C 10 Cycloalkenyl group, 3-10 membered heterocycloalkyl group, C6-C 10 an aryl group or a 5- to 10-membered heteroaryl group, R 2 is selected from hydrogen, a C1-C4 alkyl group, a C3-C6 cycloalkyl group, a 3- to 6-membered heterocycloalkyl group, or a halogen; Ring A is C6-C 10 an aryl group, a 5- to 10-membered heteroaryl group, or a 9- to 10-membered bisheterocycloalkyl group; p is 1, 2 or 3; Each R 4 each independently represent a hydrogen atom, a hydroxy group, an oxo group, a halogen atom, a cyano group, a C1-C4 alkyl group, -NH2, a C1-C4 haloalkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 hydroxyalkyl group, a hydroxy-C1-C4 haloalkyl group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, a 3- to 6-membered heterocycloalkyl group, a C3-C6 hydroxycycloalkyl group, a C1-C4 haloalkyl group substituted with a 3- to 6-membered heterocycloalkyl group, a hydroxy group, a halogen atom, -NH2, -S(O)2-(C1-C4 alkyl), or a 3- to 6-membered heterocycloalkyl group substituted with an oxo group, and the oxo group is substituted only on a non-aromatic ring; R 4 is -NR a R b and the above R a and Rb are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R 4 is -C(O)NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R 4 is -C(O)OR g and the above R g is hydrogen or a C1-C6 alkyl group, R 4 -OR h and the above R h is a C1-C6 alkyl group, Or R 4 is -(CH2)NR a R b and the above R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R 3 and R 5 are each independently hydrogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, or a C3-C6 cycloalkoxy group, and the alkyl group, alkoxy group, cycloalkyl group, and cycloalkoxy group are optionally substituted with a cyano group, a hydroxy group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, or a halogen.

[0111] Preferably, in certain embodiments of the present invention, in S5 above, R 5 is a methyl group.

[0112] In some embodiments, in the definition of each group of S5, a and R bappears at any position, each independently is hydrogen or a C1-C6 alkyl group.

[0113] In certain embodiments of the invention, S is S5′, [ka] Here, in the above S5', the above R 2 , R 3 , R 4 , R 5 , ring A and p are as defined and explained in S5.

[0114] In certain embodiments of the invention, S is -X-S5', where the structure of S5' is as described above, and X is O, NH or S, preferably O.

[0115] Preferably, in certain embodiments of the present invention, S is S5a, [ka] Here, the above R 1 , R 2 , R 3 , R 4 , ring A and p are as defined and explained in S5.

[0116] In certain embodiments of the invention, S is S5a′, [ka] Here, in the above S5a', the above R 2 , R 3 , R 4 , R 5 , ring A and p are as defined and explained in S5a.

[0117] In certain embodiments of the invention, S is -X-S5a', the structure of S5a' being as described above, and X is O, NH or S, preferably O.

[0118] More preferably, in certain embodiments of the present invention, S5 is a specific compound I-1 to I-179 of WO2019122129A1 (the entire text of which is incorporated herein by reference).

[0119] Preferably, in certain embodiments of the present invention, S is S6, [ka] Here, in the above S6, R2 is hydrogen, halogen, -OH, -CN, -NO2, a C1-C6 alkylmercapto group, or -NR a R b and R a and R b are each independently hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R2 is a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkoxy group, a C3-C6 heterocycloalkoxy group (e.g. [ka] ), C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C8 cycloalkyl group, C4-C8 cycloalkenyl group, 4- to 7-membered heterocycloalkyl group (e.g. [ka] ), 5-10 membered heterocycloalkenyl group, spiro heterocycloalkyl group, fused heterocycloalkyl group, bridged heterocycloalkyl group, phenyl group, heteroaryl group, C1-C6 haloalkyl group, -COOH, -COOR c and R c is a -C1-C6 alkyl group, a C3-C6 alkenyl group, a C3-C6 alkynyl group, a C3-C8 cycloalkyl group or a -C4-C8 cycloalkenyl group, R2 is -NS(O)(R d )(R e ) and the above Rd and R e each independently represents a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C8 cycloalkyl group, a C4-C8 cycloalkenyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group; R2 is -NHC(O)-(C1-C6 alkyl), -NHC(O)-NR a R b and the above R a and R b are each independently hydrogen, a —C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R2 is -NH-(CH2) k -NH-C(O)-R aa and the above R aa is a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group, and k is 1 or 2; R2 is -NH-(CH2) i -R f wherein i is 0, 1 or 2, and R f is a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, or a C1-C6 alkylsulfonyl group, The C1-C6 alkyl group, C1-C6 alkoxy group, 4- to 7-membered heterocycloalkyl group, and heteroaryl group may optionally be selected from the group consisting of halogen, -OH, oxo, -CN, -NO2, C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C8 cycloalkyl group, 4- to 7-membered heterocycloalkyl group, C1-C6 alkoxy group, C1-C6 haloalkyl group, C1-C6 haloalkoxy group, C1-C6 alkylsulfonyl group, phenyl group, benzyl group, heteroaryl group, -(CH2)-heteroaryl group, -NHC(O)(C1-C6 alkyl), C3-C8 cycloalkoxy group, phenoxy group, heteroaryloxy group, and -NR a R b and R a and R bare each independently selected from hydrogen, a C1-C6 alkyl group, a C3-C8 heterocycloalkyl group, or a C3-C8 cycloalkyl group; R2 is -O-(CH2) z -phenyl group, -O-(CH2) z -(4-7 membered heterocycloalkyl), -O-(CH2) z -heteroaryl group, wherein z is 0, 1 or 2, and the phenyl group, heterocycloalkyl group and heteroaryl group are optionally substituted with a group selected from -OH, heterocycloalkyl group or heterocycloalkenyl group, and can be substituted with a methyl group or an oxo group; or R2 is [ka] and R1 is hydrogen or -OR A and R A is hydrogen, C3-C 10 a cycloalkyl group or a 3- to 10-membered heterocycloalkyl group, 10 The cycloalkyl group and the 3- to 10-membered heterocycloalkyl group may optionally be substituted with one or more identical or different R a1 and / or R c1 is replaced by Each R a1 are each independently a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; and 10 Cycloalkyl groups, C6-C 10 The aryl group, the 3- to 10-membered heterocycloalkyl group, and the 5- to 10-membered heteroaryl group each independently optionally contain one or more identical or different R b1 and / or R c1 is replaced by Each R b1 are independently -ORc1 , -NR c1 R c1 , halogen, -CN, -C(O)R c1 , -C(O)OR c1 , -C(O)NR c1 R c1 , -S(O)2R c1 , -S(O)NR c1 R c1 , -NHC(O)R c1 , -N(C1-C4 alkyl)C(O)R c1 , substituted with oxo groups, and the oxo groups are substituted only on non-aromatic rings; Each R c1 are each independently hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group, Or R1 is C3-C 10 Cycloalkyl groups, C3-C 10 Cycloalkenyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; 10 Cycloalkyl groups, C3-C 10 Cycloalkenyl groups, C6-C 10 The aryl group, 3- to 10-membered heterocycloalkyl group, or 5- to 10-membered heteroaryl group may optionally be one or more R a2 and / or R b2 is replaced by Each R a2 are each independently a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; and 10 Cycloalkyl groups, C6-C 10The aryl group, 3- to 10-membered heterocycloalkyl group, or 5- to 10-membered heteroaryl group may optionally be one or more R c2 and / or R b2 is replaced by Each R b2 are independently -OR c2 , -NR c2 R c2 , halogen, -CN, -C(O)R c2 , -C(O)OR c2 , -C(O)NR c2 R c2 , -OC(O)R c2 , -S(O)2R c2 , -S(O)NR c2 R c2 , -NHC(O)R c2 , -N(C1-C4 alkyl)C(O)R c2 , -NHC(O)OR c2 , an oxo group, and =NH, and the oxo group and =NH are substituted only on non-aromatic rings; Each R c2 are each independently hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; and 10 Cycloalkyl groups, C6-C 10 The aryl group, 3- to 10-membered heterocycloalkyl group, or 5- to 10-membered heteroaryl group may optionally be one or more R d2 and / or R e2 is replaced by Each R d2 are independently -OR e2 , -NR e2 R e2 , halogen, -CN, -C(O)R e2 , -C(O)OR e2 , -C(O)NR e2 R e2 , -S(O)2R e2 , -S(O)NR e2R e2 , -NHC(O)R e2 , -N(C1-C4 alkyl)C(O)R e2 , an oxo group, said oxo group being substituted only on non-aromatic rings; Each R e2 are each independently hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; and 10 Cycloalkyl groups, C6-C 10 The aryl group, 3- to 10-membered heterocycloalkyl group, or 5- to 10-membered heteroaryl group may optionally be one or more R f2 and / or R g2 is replaced by Each R f2 are independently -OR g2 , -NR g2 R g2 , halogen, -CN, -C(O)R g2 , -C(O)OR g2 , -C(O)NR g2 R g2 , -S(O)2R g2 , -S(O)NR g2 R g2 , -NHC(O)R g2 , -N(C1-C4 alkyl)C(O)R g2 and an oxo group, wherein the oxo group is substituted only on non-aromatic rings; Each R g2 are each independently hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; or R1 is selected from a C2-C4 alkyl group, a C2-C4 alkenyl group, and the C2-C4 alkyl group and the C2-C4 alkenyl group are optionally selected from R b3is replaced by R b3 is -C(O)R c3 , -C(O)OR c3 , -C(O)NR c3 R c3 , -C(O)NHOR c3 or -C(O)N(C1-C4 alkyl)OR c3 Selected from Each R c3 are each independently hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; and 10 Cycloalkyl groups, C6-C 10 The aryl group, 3- to 10-membered heterocycloalkyl group, or 5- to 10-membered heteroaryl group may optionally be one or more R d3 and / or R e3 is replaced by Each R d3 are independently -OR e3 , -NR e3 R e3 , halogen, -CN, -C(O)R e3 , -C(O)OR e3 , -C(O)NR e3 R e3 , -S(O)2R e3 , -S(O)NR e3 R e3 , -NHC(O)R e3 , -N(C1-C4 alkyl)C(O)R e3 and an oxo group, wherein the oxo group is substituted only on non-aromatic rings; Each R e3 are each independently hydrogen, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a C3-C 10 Cycloalkyl groups, C6-C 10 an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; R3 is selected from hydrogen, a C1-C4 alkyl group, -O(C1-C4 alkyl), -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2 or halogen; R5 is selected from hydrogen, a hydroxy group, or -NHR'; R' is selected from hydrogen, a C1-C3 alkyl group, and a -C(O)C1-C3 alkyl group; R4 is selected from a C1-C4 alkyl group, a hydroxy group, an oxo group, a cyano group, a C1-C4 alkoxy group, a C1-C4 haloalkyl group, a C1-C4 hydroxyalkyl group, a hydroxy-C1-C4 haloalkyl group, a C2-C6 alkenyl group, a -C2-C6 alkynyl group, a C3-C6 cycloalkoxy group, a C3-C6 cycloalkyl group, a 3- to 6-membered heterocycloalkyl group, a 3- to 6-membered hydroxyheterocycloalkyl group, halogen, or a -SO2-C1-C4 alkyl group; R6 is selected from hydrogen, a C1-C4 alkyl group or a halogen; or R4, R6 together with the carbon atom to which they are connected represent an optionally substituted (e.g., unsubstituted or oxo) C5-C6 cycloalkyl group (e.g., [ka] and a 5- to 6-membered heterocycloalkyl group, wherein the heteroatoms in the 5- to 6-membered heterocycloalkyl group are selected from those containing 1, 2, 3, or 4 heteroatoms or heteroatom groups independently selected from —NH, —O—, —S—, and N; R7 and R8 are each independently a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, or a C3-C6 cycloalkoxy group, and the alkyl group, alkoxy group, cycloalkyl group, and cycloalkoxy group are optionally substituted with a cyano group, a hydroxy group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C3-C6 cycloalkoxy group, or a halogen.

[0120] In some embodiments, in the above S6, when R4 and R6 together with the carbon atoms connected thereto form an optionally substituted C5-C6 cycloalkyl group and a 5- to 6-membered heterocycloalkyl group, the substitution refers to substitution with 1, 2, 3, or 4 =O.

[0121] In some embodiments, in the above S6, when R4 and R6 together with the carbon atoms connected thereto form an optionally substituted 5- to 6-membered heterocycloalkyl group, [ka] The fragment is [ka] ,for example [ka] is.

[0122] In some embodiments, in S6 above, R1 is hydrogen or -OR A and R A is hydrogen.

[0123] In some embodiments, in S6 above, R1 is hydrogen.

[0124] In some embodiments, in S6 above, R2 is hydrogen, a C1-C4 alkyl group, -O(C1-C4 alkyl), -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or halogen, and the C1-C4 alkyl group and -O(C1-C4 alkyl) are each independently optionally substituted with -O(C1-C4 alkyl).

[0125] In some embodiments, in the above S6, R2 is hydrogen, a C1-C4 alkyl group, -O(C1-C4 alkyl), -NH2, -NH(C1-C4 alkyl), -N(C1-C4 alkyl)2, or halogen.

[0126] In some embodiments, in S6 above, R2 is hydrogen, a C1-C4 alkyl group, or -O(C1-C4 alkyl), and the -O(C1-C4 alkyl) is optionally substituted with -O(C1-C4 alkyl).

[0127] In some other embodiments, in S6 above, R2 is [ka] is.

[0128] In some embodiments, in the above S6, R3 is hydrogen.

[0129] In some embodiments, in the above S6, R5 is hydrogen or -NHR'.

[0130] In some embodiments, in the above S6, R4 is a C1-C4 haloalkyl group, and R6 is hydrogen or halogen, or R4 and R6 are [ka] Fragments [ka] They form a ring together with the carbon atoms to which they are attached, such that

[0131] In some embodiments, in the above S6, R7 is a C1-C6 alkyl group.

[0132] In some embodiments, in the above S6, R8 is a C1-C6 alkyl group.

[0133] In some embodiments, in S6 above, R1 is hydrogen or -OR A and R A is hydrogen, R2 is hydrogen, a C1-C4 alkyl group, or -O(C1-C4 alkyl) (e.g., a methoxy group), wherein the -O(C1-C4 alkyl) is optionally substituted with -O(C1-C4 alkyl) (e.g., a methoxy group); R3 is hydrogen; R5 is hydrogen or -NHR'; R' is selected from hydrogen, a C1-C3 alkyl group, and a -C(O)C1-C3 alkyl group; R4 is a C1-C4 haloalkyl group; R6 is hydrogen or halogen; Or R4, R6 are in S6 [ka] Fragments [ka] form a ring together with the carbon atoms to which they are attached, such that R7 is a C1-C6 alkyl group; R8 is a C1-C6 alkyl group.

[0134] In some embodiments, when R2 is a C1-C4 alkyl group in S6 above, the C1-C4 alkyl group may be a methyl group.

[0135] In some embodiments, when R2 is -O(C1-C4 alkyl) in S6 above, the -O(C1-C4 alkyl) may be -OCH3.

[0136] In some embodiments, in the above S6, R2 is hydrogen, a methyl group, -OCH3 or [ka] is.

[0137] In some embodiments, in the above S6, R2 is hydrogen, a methyl group, or -OCH3.

[0138] In some embodiments, in the above S6, R3 is hydrogen.

[0139] In some embodiments, when R' in S6 above is a C1-C3 alkyl group, the C1-C3 alkyl group may be an ethyl group or an isopropyl group.

[0140] In some embodiments, when R' is -C(O)C1-C3 alkyl in S6 above, the -C(O)C1-C3 alkyl may be -C(O)CH3.

[0141] In some embodiments, in the above S6, R5 is hydrogen or -NHR', where R' is hydrogen, an ethyl group, an isopropyl group, or -C(O)CH3.

[0142] In some preferred embodiments, in S6 above, R5 is -NHR', where R' is hydrogen.

[0143] In some embodiments, in the above S6, R4 is a C1-C4 haloalkyl group, R6 is hydrogen or halogen; Or R4, R6 are in S6 [ka] Fragments [ka] They form a ring together with the carbon atoms to which they are attached, such that

[0144] In some embodiments, when R4 in S6 above is a C1-C4 haloalkyl group, the C1-C4 haloalkyl group may be a C1-C4 fluoroalkyl group, such as a trifluoromethyl group.

[0145] In some embodiments, in the above S6, R7 is a C1-C6 alkyl group.

[0146] In some embodiments, when R7 in S6 is a C1-C6 alkyl group, the C1-C6 alkyl group may be a methyl group.

[0147] In some embodiments, in the above S6, R8 is a C1-C6 alkyl group.

[0148] In some embodiments, when R8 in S6 is a C1-C6 alkyl group, the C1-C6 alkyl group may be a methyl group.

[0149] In some embodiments, in S6 above, [ka] The fragment is [ka] may be.

[0150] In some embodiments, in S6 above, [ka] The fragment is preferably [ka] is.

[0151] In some embodiments, in S6 above, [ka] The fragment is preferably [ka] is.

[0152] In some embodiments, in S6 above, [ka] The fragment is [ka] may be, preferably [ka] is.

[0153] In some preferred embodiments, in S6 above, [ka] The fragment is [ka] is.

[0154] In some more preferred embodiments, in S6 above, [ka] The fragment is [ka] is.

[0155] Preferably, in a particular embodiment of the present invention, in the above S6, R8 is a methyl group.

[0156] In certain embodiments of the invention, S is S6′, [ka] Here, in the above S6', R2, R3, R4, R5, R6, and R7 are as defined and explained in S6.

[0157] In a specific embodiment of the present invention, in S6 and S6' above, [ka] The fragment is [ka] is.

[0158] In certain embodiments of the invention, S is -X-S6', where the structure of S6' is as described above, and X is O, NH or S, preferably O.

[0159] Preferably, in certain embodiments of the present invention, S is S6a, [ka] wherein in S6a above, R1, R2, R3, R4, R5, R6, and R7 are as defined and explained in S6.

[0160] Preferably, in certain embodiments of the present invention, in S6 or S6a above, R 1 is hydrogen and R 2 is selected from -O(C1-C4 alkyl), and R 3 is hydrogen and R 4 is a C1-C4 haloalkyl group, and R 5 is selected from -NH2, and R 7 is selected from a C1-C4 alkyl group or a C1-C4 haloalkyl group.

[0161] Preferably, in certain embodiments of the present invention, S is S6b, [ka] wherein in S6b above, R1, R2, R3, R4, R5, R6 and R7 are as defined and explained in S6.

[0162] Preferably, in certain embodiments of the present invention, S is S6c, [ka] wherein in S6c above, R2, R3, R4, R5, R6 and R7 are as defined and explained in S6.

[0163] In certain embodiments of the present invention, S is -X-S6c, the structure and definition of S6c being as described above, where X is O, NH or S, preferably O.

[0164] Preferably, in certain embodiments of the present invention, S is S6d, [ka] wherein in S6d above, X is O, NH or S, preferably O, and R2, R3, R4, R5, R6 and R7 are as defined and explained in S6.

[0165] Preferably, in certain embodiments of the present invention, S6 is a specific compound I-1 to I-383 of WO2018115380A1 (the entire text of which is incorporated herein by reference). Preferably, in certain embodiments of the present invention, S is S6e, [ka] wherein in S6e above, R2, R3 and R7 are as defined and explained in any aspect of S6.

[0166] Preferably, in certain embodiments of the present invention, S is -X-S6e, the structure and definition of S6e being as described above, where X is O, NH or S, preferably O.

[0167] Preferably, in certain embodiments of the present invention, in S6e above, R2 is -O(C1-C4 alkyl), R3 is hydrogen, and R7 is a C1-C6 alkyl group.

[0168] Preferably, in certain embodiments of the present invention, in the above S6e, R2 is -OCH3, R3 is hydrogen, and R7 is a methyl group.

[0169] In certain embodiments of the invention, S6, S6′, S6a, or S6c has any one of the following structures: [ka]

[0170] Preferably, in certain embodiments of the present invention, S6, S6', S6a or S6c above [ka] is.

[0171] Preferably, in certain embodiments of the present invention, S6, S6', S6a, S6c or S6e above [ka] is.

[0172] In certain embodiments of the present invention, S is [ka] is.

[0173] In certain embodiments of the invention, S is S6″: [ka] wherein in the above S6″, R1, R3, R4, R5, R6, R7 and R8 are as defined and explained in S6.

[0174] In certain embodiments of the invention, S is S''': [ka] wherein in S6''' above, R3, R4, R5, R6, R7 and R8 are as defined and explained in S6.

[0175] In a specific embodiment of the present invention, in the above S6" and S6'", [ka] The fragment is [ka] is.

[0176] In certain embodiments of the invention, S is -X-S6''', the structure of S6''' is as described above, where X is O, NH or S, preferably O.

[0177] Preferably, in certain embodiments of the present invention, S6″ is [ka] is.

[0178] Preferably, in certain embodiments of the present invention, S is S6a″: [ka] Here, in the above S6a'', R1, R3, R4, R5, R6, and R7 are as defined and explained in S6.

[0179] Preferably, in certain embodiments of the present invention, S is S6b″: [ka] wherein in S6b″ above, R1, R3, R4, R5, R6 and R7 are as defined and explained in S6.

[0180] Preferably, in certain embodiments of the present invention, S is S6c″: [ka] wherein in S6c'' above, R3, R4, R5, R6 and R7 are as defined and explained in S6.

[0181] Preferably, in certain embodiments of the present invention, S is -X-S6c"; the structure and definition of S6c" are as described above, where X is O, NH or S, preferably O.

[0182] Preferably, in certain embodiments of the present invention, S is S6d″: [ka] wherein in the above S6d″, X is O, NH or S, preferably O, and R3, R4, R5, R6 and R7 are as defined and explained in S6.

[0183] Preferably, in certain embodiments of the present invention, S is S6e″: [ka] wherein in S6e″ above, R3 and R7 are as defined and explained in S6.

[0184] Preferably, in certain embodiments of the present invention, S is -X-S6e"; the structure and definition of S6e" are as described above, where X is O, NH or S, preferably O.

[0185] Preferably, in certain embodiments of the present invention, in the above S6e'', R3 is hydrogen and R7 is a C1-C6 alkyl group.

[0186] Preferably, in a particular embodiment of the present invention, in the above S6e'', R3 is hydrogen and R7 is a methyl group.

[0187] Preferably, in certain embodiments of the present invention, the above S6'', S6''', S6a'', S6c'' or S6e'' [ka] is.

[0188] Preferably, in certain embodiments of the present invention, S is [ka] is.

[0189] More preferably, in certain embodiments of the present invention, S is [ka] is.

[0190] More preferably, in certain embodiments of the present invention, S is [ka] is.

[0191] In certain embodiments of the invention, L is a bond.

[0192] In certain embodiments of the invention, L is —(CH) j -, and the above -(CH2) j One or more methylene groups of - are optionally -NR 3’ -, -O-, -S-, -S(O)-, -S(O)NR 3’ -, -NR 3’ S(O)-, -S(O)2-, -S(O)2NR 3’ -, -NR 3’ S(O)2-, -NR 4’ S(O)NR 3’ -, -CR 1’ R 2’ -, -C(O)-, -C(O)O-, -OC(O)-, -NR 3’ C(O)O-, -OC(O)NR 3’ -, -C(O)NR 3’ -, -NR 3’ C(O)-, -NR4’ C(O)NR 3’ -, -P(O)-, -P(O)O-, -OP(O)-, -OP(O)O-, a vinylidene group, an ethynylene group, a 3- to 12-membered cycloalkylene group, a 3- to 12-membered heterocycloalkylene group containing one or more heteroatoms selected from N, O, and S, a 6- to 10-membered arylene group, or a 5- to 10-membered heteroarylene group, and the vinylidene group, the cycloalkylene group, the heterocycloalkylene group, the arylene group, and the heteroarylene group are each independently optionally substituted with a halogen, -OR 3’ , -NR 3’ R 4’ , oxo, nitro group, cyano group, C1-C6 alkyl group, -S(C1-C6 alkyl), C3-C 10 Cycloalkyl groups, C3-C 10 Heterocycloalkyl groups, C6-C 10 Aryl group, 5- to 10-membered heteroaryl group, -C(O)R 1’ , -C(O)OR 3’ , -OC(O)R 1’ , -C(O)NR 3’ , -NR 3’ C(O)R 1’ , -S(O)R 1’ , -S(O)NR 3’ , -S(O)2R 1’ , -S(O)NR 3’ , -NR 3’ S(O)2R 1’ , -NR 4’ S(O)NR 3’ , -OC(O)NR 3’ , -NR 4’ C(O)NR 3’ and wherein the alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group, and heteroaryl group are each independently optionally substituted with halogen, —OH, —NR 3’ R 4’ , oxo, nitro group, cyano group, C1-C6 alkyl group, C3-C 10 Cycloalkyl groups, C3-C 10substituted with one or more substituents selected from a heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; R 1’ , R 2’ are each independently a halogen, -OH, or -NR 3’ R 4’ , C1-C6 alkyl group, chloro C1-C6 alkyl group, hydroxy C1-C6 alkyl group, -O(C1-C6 alkyl), -NH(C1-C6 alkyl), -NH(C1-C6 alkyl)2, C3-C 10 Cycloalkyl groups, -O(C3-C 10 cycloalkyl), -NH(C3-C 10 Cycloalkyl), C3-C 10 Heterocycloalkyl groups, -O(C3-C 10 heterocycloalkyl), -NH(C3-C 10 heterocycloalkyl), a 6- to 10-membered aryl group, —O(6- to 10-membered aryl), —NH(6- to 10-membered aryl), a 5- to 10-membered heteroaryl group, —O(5- to 10-membered heteroaryl), —NH(5- to 10-membered heteroaryl), and R 3’ , R 4’ are each independently hydrogen, deuterium, a C1-C6 alkyl group, a C3-C 10 Cycloalkyl groups, C3-C 10 a heterocycloalkyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group, wherein j is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25.

[0193] Preferably, in certain embodiments of the present invention, L is -(CH2) j -, and the above -(CH2) j One or more methylene groups of - are optionally -NR 3’ -, -O-, -CR 1’ R 2’ -, -C(O)-, -S(O)-, -S(O)2-, -C(O)O-, -OC(O)-, -C(O)NR 3’ -, -NR 3’ C(O)-, -S(O)NR 3’-, -NR 3’ S(O)2-, vinylidene group, ethynylene group, phenyl group, 8-10 membered bicyclic arylene group, 3-7 membered saturated or partially unsaturated cycloalkylene group, 5-11 membered saturated or partially unsaturated spirocycloalkylene group, 5-11 membered saturated or partially unsaturated fused cycloalkylene group, 8-10 membered bicyclic saturated or partially unsaturated cycloalkylene group, 4-7 membered saturated or partially unsaturated heterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, 5-11 membered saturated or partially unsaturated spiroheterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, 5-11 membered saturated or partially unsaturated fused heterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur. a 8- to 10-membered bicyclic saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5- to 6-membered heteroarylene group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and the vinylidene group, ethynylene group, cycloalkylene group, heterocycloalkylene group, phenyl group, spiroheterocycloalkylene group, fused heterocycloalkylene group, spirocycloalkylene group, fused cycloalkylene group, and heteroarylene group are each independently optionally substituted with halogen, oxo, -NR 3’ R 4’ , -OR 3’ , nitro group, -CN, C1-C6 alkyl group, C3-C 10 Cycloalkyl groups, C3-C 10 and heterocycloalkyl groups, wherein the alkyl, cycloalkyl, and heterocycloalkyl groups are optionally substituted with one or more substituents selected from halogen, —OH, —NH, —CN, C1-C4 alkyl groups, and C3-C6 cycloalkyl groups; and R 1’ , R 2’are each independently halogen, —OH, —NH, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C1-C4 hydroxyalkyl group, —O(C1-C4 alkyl), —NH(C1-C4 alkyl), —NH(C1-C4 alkyl), a C3-C6 cycloalkyl group, —O(C3-C6 cycloalkyl), —NH(C3-C6 cycloalkyl), a C3-C6 heterocycloalkyl group, —O(C3-C6 heterocycloalkyl), or —NH(C3-C6 cycloalkyl); R 3’ , R 4’ are each independently hydrogen, deuterium, a C1-C4 alkyl group, a C3-C6 cycloalkyl group, or a C3-C6 heterocycloalkyl group; and j is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0194] Preferably, in certain embodiments of the present invention, L is -(CH2) j -, and the above -(CH2) j One or more methylene groups of - are optionally -NR 3’ -, -O-, -CR 1’ R 2’ -, -C(O)-, -S(O)-, -S(O)2-, -C(O)O-, -OC(O)-, -C(O)NR 3’ -, -NR 3’ C(O)-, -S(O)NR 3’ -, -NR 3’S(O)2-, vinylidene group, ethynylene group, phenyl group, 8-10 membered bicyclic arylene group, 3-7 membered saturated or partially unsaturated monocyclic cycloalkylene group, 5-11 membered saturated or partially unsaturated spirocycloalkylene group, 5-11 membered saturated or partially unsaturated fused cycloalkylene group, 8-10 membered bicyclic saturated or partially unsaturated cycloalkylene group, 5-7 membered saturated or partially unsaturated heterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen or oxygen, 5-11 membered saturated or partially unsaturated spiroheterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen or oxygen, 5-11 membered saturated or partially unsaturated spiroheterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen or oxygen, 5-11 membered saturated or partially unsaturated a fused heterocycloalkylene group, an 8- to 10-membered bicyclic saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen or oxygen, a 5- to 6-membered heteroarylene group having 1 to 4 heteroatoms independently selected from nitrogen or oxygen, or an 8- to 10-membered bicyclic heteroaryl group having 1 to 5 heteroatoms independently selected from nitrogen or oxygen, wherein the vinylidene group, ethynylene group, cycloalkylene group, heterocycloalkylene group, phenyl group, spiroheterocycloalkylene group, fused heterocycloalkylene group, fused cycloalkylene group, spirocycloalkylene group, and heteroarylene group are each independently optionally substituted with halogen, oxo, -NR 3’ R 4’ , -OR 3’ , a nitro group, -CN, a C1-C6 alkyl group, a C3-C6 cycloalkyl group, and a C3-C6 heterocycloalkyl group, wherein the alkyl group, cycloalkyl group, and heterocycloalkyl group are optionally substituted with one or more substituents selected from halogen, -OH, -NH2, -CN, a C1-C4 alkyl group, and a C3-C6 cycloalkyl group; R 1’ , R 2’are each independently halogen, —OH, —NH, a C1-C4 alkyl group, a C1-C4 haloalkyl group, a C1-C4 hydroxyalkyl group, —O(C1-C4 alkyl), —NH(C1-C4 alkyl), —NH(C1-C4 alkyl), a C3-C6 cycloalkyl group, —O(C3-C6 cycloalkyl), —NH(C3-C6 cycloalkyl), a C3-C6 heterocycloalkyl group, —O(C3-C6 heterocycloalkyl), or —NH(C3-C6 cycloalkyl); R 3’ , R 4’ are each independently hydrogen, deuterium, a C1-C4 alkyl group, a C3-C6 cycloalkyl group, or a C3-C6 heterocycloalkyl group; and j is 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0195] Preferably, in certain embodiments of the present invention, L is -(CH2) j -, and the above -(CH2) j One, two, three, four or five methylene groups among - are optionally selected from -NH-, -NCH3-, -O-, -C(CH3)2-, -CHF-, -CHCF3-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH3-, -NHC(O)-, -NCH3C(O)-, vinylidene group, ethynylene group, cyclopropylidene group, cyclobutylidene group, cyclopentylidene group, cyclohexylidene group, oxacyclopropylidene group, oxacyclobutylidene group, oxacyclo a thiazolylidene group, an oxacyclohexylidene group, an azacyclopropylidene group, an azacyclobutylidene group, an azacyclopentylidene group, a piperidylidene group, a piperazilidine group, a morpholinoline group, a hypomorpholino group, a phenylene group, a pyrrolidine group, a thienylene group, a furylene group, an imidazolidene group, a pyrazolylene, a triazolylene, a tetrazolylene, an oxazolylene, an isoxazolylene, a thiazolylene, an isothiazolylene, a pyridylene group, a pyrimidinylidene group, a pyridazilidene group, a pyrazinylene group, [ka] and the substituents are optionally selected from halogen, oxo, -NR3’ R 4’ , -OR 3’ , C1-C4 alkyl groups, the alkyl groups being optionally substituted with one or more substituents selected from halogen, —OH, —NH2; R 3’ , R 4’ are each independently hydrogen, deuterium, or a C1-C4 alkyl group; and j is 2, 3, 4, 5, 6, 7, 8, 9, or 10.

[0196] Preferably, in certain embodiments of the present invention, L is -(CH2) j -, and the above -(CH2) j One, two, three, four or five methylene groups among - are optionally selected from -NH-, -NCH3-, -O-, -C(CH3)2-, -CHF-, -CHCF3-, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH3-, -NHC(O)-, -NCH3C(O)-, a cyclopropylidene group, a cyclobutylidene group, a cyclopentylidene group, a cyclohexylidene group, an oxacyclopropylidene group, an oxacyclobutylidene group, an oxacyclopentylidene group, an oxacyclohexylidene group, an azacyclopropylidene group, an azacyclobutylidene group, an azacyclopentylidene group, a piperidylidene group, a piperazilidene group, a morpholinoline group, a hypomorpholino group, [ka] and the substituents are optionally substituted with a group selected from F, Cl, oxo, -NR 3’ R 4’ , -OR 3’ , C1-C4 alkyl groups, the alkyl groups being optionally substituted with one or more substituents selected from halogen, —OH, —NH2; R 3’ , R 4’ are each independently hydrogen, deuterium, a methyl group, an ethyl group, or a propyl group; and j is 3, 4, 5, 6, 7, 8, 9, or 10.

[0197] Preferably, in certain embodiments of the present invention, L is -(CH2) j -, and the above -(CH2) j One, two, three, four or five methylene groups among - are optionally selected from -O-, -NH-, -NCH3-, -C(O)-, -C(O)NH-, -NHC(O)-, -NCH3C(O)-, -C(O)NCH3-, a cyclohexylidene group, an azacyclopropylidene group, an azacyclobutylidene group, an azacyclopentylidene group, a piperidylidene group, a piperazilidine group, [ka] and j is 4, 5, 6, 7, 8, 9 or 10.

[0198] Preferably, in certain embodiments of the present invention, L is -(CH2) j-1 -C(O)-, and the above -(CH2) j-1 The methylene group in —C(O)— is as defined for L above and is optionally substituted with one or more groups, and j is as defined for L above.

[0199] Preferably, in certain embodiments of the present invention, L is [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

change

[0200] In certain embodiments of the invention, L is any one of the following structures: [ka] [ka]

[0201] Preferably, in certain embodiments of the invention, L is LA, [ka] Here, in the above LA, Ring A is a bond, C3-C 12 Cycloalkylene groups (e.g. [ka] wherein the a end is linked to S and the b end is linked to X''') or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, or S (e.g., [ka] wherein the a end is connected to S and the b end is connected to X''', and the cycloalkylene and heterocycloalkylene groups are optionally substituted with a substituent selected from halogen, oxo, cyano, amino, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or -O-(C1-C6 alkyl); Ring B is a bond, C3-C 12 Cycloalkylene groups (e.g., [ka] wherein the c-terminus is linked to X''' and the d-terminus is linked to L3), or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, or S (e.g., [ka] wherein the c-terminus is linked to X''' and the d-terminus is linked to L3), and the cycloalkylene and heterocycloalkylene groups are optionally substituted with a substituent selected from halogen, oxo, cyano, amino, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or -O-(C1-C6 alkyl); Ring C is C3-C 12 Cycloalkylene groups (e.g. [ka] wherein the e end is connected to L3 and the f end is connected to X″), or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, or S (e.g., [ka] wherein the e end is connected to L3 and the f end is connected to X″), and the cycloalkylene group and heterocycloalkylene group are optionally substituted with a substituent selected from halogen, oxo, cyano, amino, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or —O—(C1-C6 alkyl); X'' is a bond, -NH-, -NCH3-, -O-, -C(CH3)2-, -S-, -C=C-, -C≡C-, -CHF-, -CHCF3-, -C(O)-, -S(O)-, -S(O)2-, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH3-, -NHC(O)-, -NCH3C(O)- or -C(O)CHO-; L3 is -(CH2) k wherein one or two methylene groups in L3 are optionally substituted with a group selected from -O-, -NH-, -C≡C-, -N(C-C alkyl)-, -N(C-C haloalkyl)-, -C(O)-, -N(C-C hydroxyalkyl)-, or -N(C-C cycloalkyl)-; and k is 0, 1, 2, 3, 4, 5, 6, or 7; X''' is a bond, -NH-, -NCH3-, -O-, -C(CH3)2-, -S-, -C=C-, -C≡C-, -CHF-, -CHCF3-, -C(O)-, -S(O)-, -S(O)2-, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH3-, -CH2NCH3-, -NHC(O)- or -NCH3C(O)-.

[0202] In some embodiments, in the above L A , Ring A is a bond, C3-C 12a cycloalkylene group or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, and S, wherein the cycloalkylene group and heterocycloalkylene group are optionally substituted with a substituent selected from halogen, oxo, cyano, amino, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or -O-(C1-C6 alkyl); Ring B is a bond, C3-C 12 a cycloalkylene group or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, and S, wherein the cycloalkylene group and heterocycloalkylene group are optionally substituted with a substituent selected from halogen, oxo, cyano, amino, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or -O-(C1-C6 alkyl); Ring C is C3-C 12 a cycloalkylene group or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, and S, wherein the cycloalkylene group and heterocycloalkylene group are optionally substituted with a substituent selected from halogen, oxo, cyano, amino, hydroxy, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, or -O-(C1-C6 alkyl); X'' is a bond, -NH-, -NCH3-, -O-, -C(CH3)2-, -S-, -C=C-, -C≡C-, -CHF-, -CHCF3-, -C(O)-, -S(O)-, -S(O)2-, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH3-, -NHC(O)- or -NCH3C(O)-; L3 is -(CH2) k wherein one or two methylene groups in L3 are optionally substituted with a group selected from -O-, -NH-, -N(C1-C6 alkyl)-, -N(C1-C6 haloalkyl)-, -N(C1-C6 hydroxyalkyl)-, or -N(C3-C8 cycloalkyl)-; and k is 0, 1, 2, 3, or 4; X''' is a bond, -NH-, -NCH3-, -O-, -C(CH3)2-, -S-, -C=C-, -C≡C-, -CHF-, -CHCF3-, -C(O)-, -S(O)-, -S(O)2-, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH3-, -NHC(O)- or -NCH3C(O)-.

[0203] In certain embodiments of the present invention, in the above L A , L is —(CH) k wherein one or two methylene groups in L3 are optionally substituted with a group selected from -O-, -NH-, -C≡C-, -N(C-C alkyl)-, -N(C-C haloalkyl)-, -N(C-C hydroxyalkyl)-, or -N(C-C cycloalkyl)-; and k is 0, 1, 2, 3, 4, 5, 6, or 7.

[0204] Preferably, in certain embodiments of the present invention, in the above LA, ring A is a bond.

[0205] Preferably, in a specific embodiment of the present invention, in the above L A, ring A is a 3- to 7-membered saturated or partially unsaturated cycloalkylene group, a 4- to 11-membered saturated or partially unsaturated spirocycloalkylene group, a 4- to 11-membered saturated or partially unsaturated fused cycloalkylene group, an 8- to 10-membered bicyclic saturated or partially unsaturated cycloalkylene group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4- to 11-membered saturated or partially unsaturated spiroheterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4- to 11-membered saturated or partially unsaturated fused heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8- to 10-membered bicyclic saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0206] Preferably, in a specific embodiment of the present invention, in the above L A, ring A is a 3- to 6-membered saturated cycloalkylene group or a 4- to 7-membered saturated monocyclic heterocycloalkylene group having 1 or 2 heteroatoms independently selected from nitrogen.

[0207] Preferably, in certain embodiments of the present invention, in the above LA, ring A is a cyclohexylidene group (e.g., cyclohexane-1,4-diyl, e.g., trans cyclohexane-1,4-diyl), a piperidylidene group (e.g., piperidine-1,4-diyl), or a piperazilidene group (e.g., piperazine-1,4-diyl).

[0208] In certain embodiments of the present invention, in the above L A , ring A is [ka] where the a-terminus is linked to S and the b-terminus is linked to X'''.

[0209] In certain embodiments of the present invention, in the above L A , ring A is [ka] where the a-terminus is linked to S and the b-terminus is linked to X'''.

[0210] In certain embodiments of the present invention, in the above L A , ring A is [ka] where the a-terminus is linked to S and the b-terminus is linked to X'''.

[0211] Preferably, in certain embodiments of the present invention, in the above LA, ring B is a bond.

[0212] Preferably, in a specific embodiment of the present invention, in the above L A, ring B is a 3- to 7-membered saturated or partially unsaturated cycloalkylene group, a 4- to 11-membered saturated or partially unsaturated spirocycloalkylene group, a 4- to 11-membered saturated or partially unsaturated fused cycloalkylene group, an 8- to 10-membered bicyclic saturated or partially unsaturated cycloalkylene group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4- to 11-membered saturated or partially unsaturated spiroheterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4- to 11-membered saturated or partially unsaturated fused heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8- to 10-membered bicyclic saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0213] Preferably, in a specific embodiment of the present invention, in the above L A, ring B is a 4- to 7-membered saturated monocyclic heterocycloalkylene group containing one or two nitrogen heteroatoms, a 7- to 11-membered spiroheterocycloalkylene group containing one or two nitrogen heteroatoms, or a fused heterocycloalkylene group.

[0214] Preferably, in certain embodiments of the present invention, in the above LA, ring B is a piperidylidene group (eg, piperidine-1,4-diyl) or a piperazilidene group (eg, piperazine-1,4-diyl).

[0215] In certain embodiments of the present invention, in the above L A, ring B is [ka] where the c-terminus is linked to X''' and the d-terminus is linked to L3.

[0216] Preferably, in certain embodiments of the present invention, ring B is [ka] where the c-terminus is linked to X''' and the d-terminus is linked to L3.

[0217] Preferably, in a specific embodiment of the present invention, in the above L A, ring C is a 3- to 7-membered saturated or partially unsaturated cycloalkylene group, a 4- to 11-membered saturated or partially unsaturated spirocycloalkylene group, a 4- to 11-membered saturated or partially unsaturated fused cycloalkylene group, an 8- to 10-membered bicyclic saturated or partially unsaturated cycloalkylene group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4- to 11-membered saturated or partially unsaturated spiroheterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4- to 11-membered saturated or partially unsaturated fused heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8- to 10-membered bicyclic saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0218] Preferably, in a specific embodiment of the present invention, in the above L A, ring C is a 4- to 7-membered saturated monocyclic heterocycloalkylene group containing one or two nitrogen heteroatoms, a 7- to 11-membered spiroheterocycloalkylene group containing one or two nitrogen heteroatoms, or a fused heterocycloalkylene group.

[0219] Preferably, in a specific embodiment of the present invention, in the above LA, ring C is a piperidylidene group (e.g., piperidine-1,4-diyl), a piperazilidene group (e.g., piperazine-1,4-diyl), [ka] )

[0220] In certain embodiments of the present invention, in the above L A, ring C is [ka] where the e end is linked to L3 and the f end is linked to X″.

[0221] In certain embodiments of the present invention, in the above L A, ring C is [ka] where the e end is linked to L3 and the f end is linked to X″.

[0222] Preferably, in a specific embodiment of the present invention, in the above L A, ring A is a 3- to 6-membered saturated cycloalkylene group, ring B is a 4- to 7-membered saturated monocyclic heterocycloalkylene group containing one or two nitrogen heteroatoms, ring C is a 4- to 7-membered saturated monocyclic heterocycloalkylene group containing one or two nitrogen heteroatoms, a 7- to 11-membered spiroheterocycloalkylene group or a fused heterocycloalkylene group containing one or two nitrogen heteroatoms, X″ is a bond or —C(O)—, and L3 is —(CH2) k and k is 1, 2, 3, 4, or 5 (e.g., k is 1, 2, 3, or 4).

[0223] Preferably, in certain embodiments of the present invention, in the above L A , X″ is a bond or —C(O)—.

[0224] Preferably, in certain embodiments of the present invention, in the above LA, X'' is a bond.

[0225] Preferably, in a particular embodiment of the present invention, in the above L A , X″ is —C(O)—.

[0226] Preferably, in a particular embodiment of the present invention, in the above L A , X″ is —C(O)CH 2 O—.

[0227] Preferably, in certain embodiments of the present invention, in the above L A , X′″ is a bond or —C(O)—.

[0228] Preferably, in certain embodiments of the present invention, in the above LA, X''' is a bond.

[0229] Preferably, in a specific embodiment of the present invention, in the above L A , X′″ is —C(O)—.

[0230] Preferably, in certain embodiments of the present invention, k is 1, 2, 3, 4 or 5 in the above LA.

[0231] Preferably, in a specific embodiment of the present invention, in the above L A, L is -(CH) k and k is 1, 2, 3, 4 or 5.

[0232] Preferably, in a specific embodiment of the present invention, in the above L A, L is -(CH) k wherein one or two methylene groups in L3 are optionally replaced with -O-, -NH-, -C≡C-, or -N(C1-C6 alkyl)- (e.g., -N(CH3)-), and k is 1, 2, 3, 4, or 5.

[0233] Preferably, in certain embodiments of the present invention, in the above L A, k is 1, 2, 3 or 4. Preferably, in certain embodiments of the present invention, in the above L A, L is -(CH) k -, wherein one or two CH2 contained in L3 are each independently optionally substituted with -O-, -NH- or -N(C1-C6 alkyl)- (e.g., -N(CH3)-), or one -CH2CH2- contained in L3 is optionally substituted with -C≡C-, and k is 1, 2, 3 or 4.

[0234] Preferably, in a specific embodiment of the present invention, in the above L A, L is -(CH) k wherein one methylene group in L3 is optionally substituted with an -O-, -NH-, or -N(C1-C6 alkyl)- (e.g., -N(CH3)-) group; and k is 1, 2, 3, or 4.

[0235] Preferably, in certain embodiments of the invention, the LA is LA-1, [ka] Here, the ring A, ring B, ring C, L3, and X'' are as defined and explained in LA.

[0236] In certain embodiments of the invention, the LA is LA-2, [ka] Here, ring A is [ka] wherein the a-terminus is linked to S, the b-terminus is linked to X''', and 1, 2, 3 or 4 hydrogen atoms in the ring A are optionally substituted with F; X''' is -C(O)-; Ring B is [ka] wherein the c-terminus is linked to X''', the d-terminus is linked to L3, and 1, 2, 3 or 4 hydrogen atoms in ring B are optionally substituted with F; L3 is -(CH2) k -, wherein one or two CH2 contained in L3 are each independently optionally substituted with -O-, -NH- or -N(C1-C6 alkyl)- (e.g., -N(CH3)-), or one -CH2CH2- contained in L3 is optionally substituted with -C≡C-, and k is 1, 2, 3 or 4; Ring C is [ka] wherein the e end is linked to L3, the f end is linked to X″, and 1, 2, 3 or 4 hydrogen atoms in the ring C are optionally substituted with F; X'' is -C(O)-.

[0237] Preferably, in certain embodiments of the present invention, in the above LA, LA-1 and LA-2, ring A is [ka] where the a-terminus is linked to S and the b-terminus is linked to X'''.

[0238] Preferably, in certain embodiments of the present invention, ring B is [ka] where the c-terminus is linked to X''' and the d-terminus is linked to L3.

[0239] In a specific embodiment of the present invention, in the above LA, LA-1 and LA-2, L3 is -(CH2) k wherein one or two CH2 contained in L3 are each independently optionally replaced with -O-, -NH- or -N(CH3)-; and k is 1, 2, 3 or 4.

[0240] In a specific embodiment of the present invention, in the above LA, LA-1 and LA-2, L3 is -(CH2) k wherein one or two CH2 contained in L3 are each independently optionally substituted with -O-; and k is 1, 2, 3, or 4.

[0241] Preferably, in certain embodiments of the present invention, k is 3 or 4, preferably 4, in the above LA, LA-1 and LA-2.

[0242] Preferably, in certain embodiments of the present invention, in the above LA, LA-1 and LA-2, L3 is -(CH2) k wherein one CH2 contained in L3 is optionally substituted with -O-; and k is 4.

[0243] In a specific embodiment of the present invention, in the above LA, LA-1 and LA-2, L3 is -CH2-, -(CH2)2-, -(CH2)3-, -(CH2)4-, [ka] wherein the k″ end is connected to ring B and the k′ end is connected to ring C.

[0244] Preferably, in a specific embodiment of the present invention, in the above LA, LA-1 and LA-2, L3 is -(CH2)4-, [ka] may be.

[0245] Preferably, in certain embodiments of the present invention, in the above LA, LA-1 and LA-2, ring C is [ka] where the e end is linked to L3 and the f end is linked to X″.

[0246] In certain embodiments of the invention, LA-2 has any one of the following structures: [ka] [ka]

[0247] Preferably, in certain embodiments of the invention, LA-2 has any one of the following structures: [ka]

[0248] In a particular embodiment of the invention, the LA is LA-3: [ka] Here, ring A is [ka] wherein the a-terminus is linked to S, the b-terminus is linked to X''', and 1, 2, 3 or 4 hydrogen atoms in the ring A are optionally substituted with F; X''' is -C(O)-; Ring B is [ka] wherein the c-terminus is linked to X''', the d-terminus is linked to L3, and 1, 2, 3 or 4 hydrogen atoms in ring B are optionally substituted with F; L3 is -(CH2) k -, wherein one CH2 contained in L3 is optionally substituted with -O-, -NH-, or -N(C1-C6 alkyl)- (e.g., -N(CH3)-), and k is 1 or 2; Ring C is [ka] wherein the e end is linked to L3, the f end is linked to X″, and 1, 2, 3 or 4 hydrogen atoms in the ring C are optionally substituted with F; X'' is -C(O)-.

[0249] Preferably, in certain embodiments of the present invention, in the above LA, LA-1 and LA-3, ring A is [ka] and preferably [ka] where the a-terminus is linked to S and the b-terminus is linked to X'''.

[0250] Preferably, in certain embodiments of the present invention, in the above LA, LA-1 and LA-3, ring B is [ka] where the c-terminus is linked to X''' and the d-terminus is linked to L3.

[0251] Preferably, in certain embodiments of the present invention, in the above LA, LA-1 and LA-3, L3 is -(CH2) k - and k is 1 or 2.

[0252] Preferably, in certain embodiments of the present invention, in the above LA, LA-1 and LA-3, ring C is [ka] where the c-terminus is linked to X''' and the d-terminus is linked to L3.

[0253] In certain embodiments of the invention, LA-3 has any one of the following structures: [ka]

[0254] Preferably, in certain embodiments of the invention, the LA-3 has any one of the following structures: [ka]

[0255] In a particular embodiment of the invention, the LA is LA-4: [ka] Here, ring A is [ka] wherein the a-terminus is linked to S, the b-terminus is linked to X''', and 1, 2, 3 or 4 hydrogen atoms in the ring A are optionally substituted with F; X''' is a bond, -C(O)NH- or -C(O)NCH3-; Ring B is a bond, L3 is -(CH2) k wherein one or two methylene groups in L3 are optionally substituted with -O-, -NH-, -C(O)-, -C≡C- or -N(C1-C6 alkyl)-, and k is 0, 1, 2, 3, 4, 5, 6 or 7; Ring C is [ka] wherein the e end is linked to L3, the f end is linked to X″, and 1, 2, 3 or 4 hydrogen atoms in the ring C are optionally substituted with F; X'' is -C(O)-.

[0256] In a specific embodiment of the present invention, in the above LA-4, ring A is [ka] where the a-terminus is linked to S and the b-terminus is linked to X'''.

[0257] In a specific embodiment of the present invention, in the above LA-4, L3 is -CH2-, [ka] where the k″ end is linked to ring B and the k′ end is linked to ring C.

[0258] In a specific embodiment of the present invention, in the above LA-4, ring C is [ka] where the e end is linked to L3 and the f end is linked to X″.

[0259] In certain embodiments of the invention, the LA-4 has any one of the following structures: [ka]

[0260] Preferably, in certain embodiments of the invention, the LA-4 has any one of the following structures: [ka]

[0261] In a particular embodiment of the invention, the LA is LA-5: [ka] wherein ring A, X''', ring B, L3 and ring C are as defined in LA-2 or LA-3; X″ is —C(O)CH2O—, and —C(O)— in X″ is linked to the ring C.

[0262] In a specific embodiment of the present invention, in the above LA-5, ring A is [ka] where the a-terminus is linked to S and the b-terminus is linked to X'''.

[0263] In a specific embodiment of the present invention, in the above LA-5, ring B is [ka] where the c-terminus is linked to X''' and the d-terminus is linked to L3.

[0264] In a specific embodiment of the present invention, in the above LA-5, L3 is -(CH2) k and k is 1 or 2, preferably 1.

[0265] In a specific embodiment of the present invention, in the above LA-5, ring C is [ka] where the e end is linked to L3 and the f end is linked to X″.

[0266] Preferably, in certain embodiments of the present invention, the LA-5 is [ka] is.

[0267] Preferably, in certain embodiments of the present invention, the LA is [ka] [ka] [ka] [ka] is.

[0268] Preferably, in certain embodiments of the invention, E is a CRBN, VHL, XAIP or MDM2 E3 ubiquitin ligase small molecule ligand.

[0269] Preferably, in certain embodiments of the present invention, E is E1, E1a, E1b or E1c [ka] and Wherein, E1, E1a, E1b or E1c above: Each R 1 are each independently a halogen, an optionally substituted acyl group, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aryl group, an optionally substituted heteroaryl group, —CN or —O(CH) X R 1A and and at least one R 1 is -O(CH2) x R 1A and R 6 is an unsubstituted isopropyl group, —(CH)C(O)OMe or —(CH)OH, R 6A is the alkyl group to be substituted, R 7 is hydrogen, an optionally substituted acyl group, an optionally substituted alkyl group or a nitrogen protecting group; R 1A is hydrogen, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted carbocycle, an optionally substituted heterocycle, an optionally substituted aryl group, an optionally substituted heteroaryl group, -OR A , -N(R B )2, or -SR A and Each R A are each independently hydrogen, an optionally substituted acyl group, or an optionally substituted alkyl group, and are an oxygen protecting group when connected to O, or a sulfur protecting group when connected to S; Each R B are each independently hydrogen, an optionally substituted acyl group, an optionally substituted alkyl group, or a nitrogen protecting group; n is 1, 2, 3 or 4, and x is 0, 1, 2, 3, 4, 5 or 6, and R 6 is an isopropyl group, R 6A is a methyl group, R 7 is hydrogen, and when n is 1, R 1 is not a methyl group or a hydroxymethyl group.

[0270] Preferably, in certain embodiments of the invention, E is E2, [ka] Here, in the above E2, X 101 is a bond, -CH2-, -CHCF3-, -S(O)2-, -S(O)-, -P(O)R 100 -, -P(O)OR 100 -, -P(O)N(R 100 )2, -C(O)-, -C(S)-, or [ka] and X 201 is C or Si, X 301 -CH2-, -O-, -S-, -C(R 100 )2- or -Si(R 100 )2- and R 101 is hydrogen, deuterium, halogen, -CN, -OR 100 , -SR 100 , -S(O)R 100 , -S(O)2R 100 , -N(R 100 )2, -P(O)(OR 100 )2, -P(O)[N(R 100 )2](OR 100 ), -P(O)[N(R 100 )2]2, -Si(OH)2(R 100 )-, -Si(OH)(R 100 )2-, -Si(R 100 )3-, or an optionally substituted C1-C4 alkyl group; R 201 is hydrogen, -R 601 , halogen, -CN, -NO2, -OR 100 , -SR 100 , -S(O)R 100 , -S(O)2R 100 , -N(R 100 )2, -S(O)2N(R 100 )2, -C(O)R 100 , -C(O)OR 100 , -C(O)N(R 100 )2, -OC(O)R 100 , -OC(O)N(R 100 )2, -NR 100C(O)OR 100 , -NR 100 C(O)R 100 , -NR 100 C(O)N(R 100 )2, -OP(O)(R 100 )2, -OP(O)(OR 100 )2, -OP(O)(OR 100 )[N(R 100 )2], -OP(O)[N(R 100 )2], -NP(O)(R 100 )2, -NR 100 P(O)(OR 100 )2, -N(R 100 )P(O)(OR 100 )[N(R 100 )2], -N(R 100 )P(O)[N(R 100 )2]2, or -NR 100 S(O)2R 100 Selected from L 101 is a bond or a C1-C4 alkylene group, and one or two methylene groups of the C1-C4 alkylene group are optionally selected from -O-, -C(O)-, -C(S)-, -C(R 100 )2-, -CH(R 100 )-, -C(F)2-, -N(R 100 )-, -S-, -S(O)2- or -CH=CH, Ring A is a bicyclic or tricyclic ring; [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] Selected from where: Ring B is a 6-membered heteroaryl group containing 1 to 2 N atoms, a phenyl group, a 5- to 7-membered saturated or partially unsaturated cycloalkyl group, a 5- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O and S, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms selected from N, O and S; R 301 is hydrogen, halogen, -OR 100 , -SR 100 or -N(R 100 )2 are selected, R 401 is hydrogen, -R 601 , -halogen, -CN, nitro group, -OR 100 , -SR 100 , -N(R 100 )2, -S(O)R 100 , -S(O)2R 100 , -N(R 100 )2, -S(O)2N(R 100 )2, -C(O)R 100 , -C(O)OR 100 , -C(O)N(R 100 )2, -OC(O)R 100 , -OC(O)N(R 100 )2, -NR 100 C(O)OR 100 , -NR 100 C(O)R 100 , -NR 100 C(O)N(R 100 )2 or -NR 100 S(O)2R 100 and R 501 is hydrogen, —CN, or a C1-C4 alkyl group, R 601is an optionally substituted C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, or a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S; R 100 is selected from hydrogen, an optionally substituted C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S, or two R 100 form, together with the N atom linked thereto, a saturated or partially unsaturated 4- to 7-membered heteroaryl group further containing 0 to 3 heteroatoms selected from N, O and S linked to the N atom; m'' is 0, 1, 2, 3 or 4.

[0271] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E3, [ka] Here, in E3 above, X 101 is a bond, -CH2-, -CHCF3-, -S(O)2-, -S(O)-, -P(O)R 100 -, -P(O)OR 100 -, -P(O)N(R 100 )2, -C(O)-, -C(S)-, or [ka] and X 201 is C, N or Si, X 301 -CH2-, -O-, -S-, -C(R 100 )2- or -Si(R 100 )2- and R 101is hydrogen, deuterium, halogen, -CN, -OR 100 , -SR 100 , -S(O)R 100 , -S(O)2R 100 , -N(R 100 )2, -P(O)(OR 100 )2, -P(O)[N(R 100 )2](OR 100 ), -P(O)[N(R 100 )2]2, -Si(OH)2(R 100 )-, -Si(OH)(R 100 )2-, -Si(R 100 )3-, or an optionally substituted C1-C4 alkyl group; L 101 is a bond or a C1-C4 alkylene group, and one or two methylene groups of the C1-C4 alkylene group are optionally selected from -O-, -C(O)-, -C(S)-, -C(R 100 )2-, -CH(R 100 )-, -C(F)2-, -N(R 100 )-, -S-, -S(O)2- or -CH=CH, Ring A is absent, a monocyclic ring or a bicyclic ring; [ka] [ka] [ka] [ka] [ka] Selected from R 201 is hydrogen, -R 601 , halogen, -CN, -NO2, -OR 100 , -SR 100 , -S(O)R 100 , -S(O)2R 100 , -N(R 100)2, -S(O)2NR 100 , -C(O)R 100 , -C(O)OR 100 , -C(O)N(R 100 )2, -OC(O)R 100 , -OC(O)N(R 100 )2, -NR 100 C(O)OR 100 , -NR 100 C(O)R 100 , -NR 100 C(O)N(R 100 )2, -OP(O)(R 100 )2, -OP(O)(OR 100 )2, -OP(O)(OR 100 )[N(R 100 )2], -OP(O)[N(R 100 )2], -NP(O)(R 100 )2, -NR 100 P(O)(OR 100 )2, -N(R 100 )P(O)(OR 100 )[N(R 100 )2], -N(R 100 )P(O)[N(R 100 )2]2, or -NR 100 S(O)2R 100 Selected from Ring B is a 6-membered heteroaryl group containing 1 to 2 N atoms, a phenyl group, a 5- to 7-membered saturated or partially unsaturated cycloalkyl group, a 5- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O and S, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms selected from N, O and S; R 301 and R 401 are each independently hydrogen, -R 601 , halogen, -CN, -NO2, -OR 100 , -SR 100 , -S(O)R 100 , -S(O)2R 100 , -N(R 100 )2, -S(O)2NR 100 , -C(O)R 100 , -C(O)OR 100 , -C(O)N(R 100)2, -OC(O)R 100 , -OC(O)N(R 100 )2, -NR 100 C(O)OR 100 , -NR 100 C(O)R 100 , -NR 100 C(O)N(R 100 )2 or -NR 100 S(O)2R 100 and R 501 is hydrogen, —CN, or a C1-C4 alkyl group, R 601 is an optionally substituted C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, or a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S; R 100 is selected from hydrogen, an optionally substituted C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, or S, or two R 100 together with the N atom linked thereto, form a saturated or partially unsaturated 4- to 7-membered heteroaryl group further containing 0 to 3 heteroatoms selected from N, O, or S linked to the N atom; P″ is 0 or 1; m″ is 0, 1 or 2; n'' is 0, 1, 2, 3 or 4.

[0272] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E4, [ka] Here, in E4 above, X 101is a bond, -CH2-, -CHCF3-, -S(O)2-, -S(O)-, -P(O)R 100 -, -P(O)OR 100 -, -P(O)N(R 100 )2, -C(O)-, -C(S)-, or [ka] and X 201 is C, N or Si, X 301 -CH2-, -O-, -S-, -C(R 100 )2- or -Si(R 100 )2- and R 101 is hydrogen, deuterium, halogen, -CN, -OR 100 , -SR 100 , -S(O)R 100 , -S(O)2R 100 , -N(R 100 )2, -P(O)(OR 100 )2, -P(O)[N(R 100 )2](OR 100 ), -P(O)[N(R 100 )2]2, -Si(OH)2(R 100 )-, -Si(OH)(R 100 )2-, -Si(R 100 )3-, or an optionally substituted C1-C4 alkyl group; L 101 is a bond or a C1-C4 alkylene group, and one or two methylene groups of the C1-C4 alkylene group are optionally selected from -O-, -C(O)-, -C(S)-, -C(R 100 )2-, -CH(R 100 )-, -C(F)2-, -N(R 100 )-, -S-, -S(O)2- or -CH=CH, R 201 is hydrogen, -R 601 , halogen, -CN, -NO2, -OR 100 , -SR 100 , -S(O)R 100 , -S(O)2R 100 , -N(R100 )2, -S(O)2NR 100 , -C(O)R 100 , -C(O)OR 100 , -C(O)N(R 100 )2, -OC(O)R 100 , -OC(O)N(R 100 )2, -NR 100 C(O)OR 100 , -NR 100 C(O)R 100 , -NR 100 C(O)N(R 100 )2, -OP(O)(R 100 )2, -OP(O)(OR 100 )2, -OP(O)(OR 100 )[N(R 100 )2], -OP(O)[N(R 100 )2], -NP(O)(R 100 )2, -NR 100 P(O)(OR 100 )2, -N(R 100 )P(O)(OR 100 )[N(R 100 )2], -N(R 100 )P(O)[N(R 100 )2]2, or -NR 100 S(O)2R 100 Selected from R 601 is an optionally substituted C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, or a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S; R 100 is selected from hydrogen, an optionally substituted C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, or S, or two R 100 together with the N atom linked thereto, form a saturated or partially unsaturated 4- to 7-membered heteroaryl group further containing 0 to 3 heteroatoms selected from N, O, or S linked to the N atom; ring E, ring F, and ring G each independently represent a 6-membered heteroaryl group containing 1 to 2 N atoms, a phenyl group, a 5- to 7-membered saturated or partially unsaturated cycloalkyl group, a 5- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, and S, or a 5-membered heteroaryl group containing 1 to 3 heteroatoms selected from N, O, and S; m'' is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16.

[0273] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E5, [ka] Here, in the above E5, the ring M is [ka] Selected from each X 101 , X 601 and X 701 each independently represents a bond, -CH2-, -CHCF3-, -S(O)2-, -S(O)-, or -P(O)R 100 -, -P(O)OR 100 -, -P(O)N(R 100 )2, -C(O)-, -C(S)-, or [ka] and each X 301 and X 501 are each independently a bond, -C(R 100 )2-, -NR 100 -, -O-, -S-, or -Si(R 100 )2- and X 401 teeth, [ka] Selected from Each R 100 are each independently selected from hydrogen, an optionally substituted C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S, or two R 100 form, together with the N atom linked thereto, a group further containing 0 to 3 heteroatoms selected from N, O and S linked to the N atom, Each R 301a are independently hydrogen, deuterium, and -R 601 , halogen, -CN, -NO2, -OR 100 , -SR 100 , -N(R 100 )2, -Si(R 100 )3, -S(O)R 100 , -S(O)2R 100 , -S(O)2N(R 100 )2, -C(O)R 100 , -C(O)OR 100 , -C(O)N(R 100 )2, -C(O)N(R 100 ) OR 100 , -C(R 100 )2N(R 100 )C(O)R 100 , -C(R 100 )2N(R 100 )C(O)N(R 100 )2, -OC(O)R 100 , -OC(O)N(R 100 )2, -NR 100 C(O)OR 100 , -NR 100 C(O)R 100 , -NR 100 C(O)N(R 100 )2, -OP(O)(R 100 )2, -OP(O)(OR 100 )2, -OP(O)(OR 100 )[N(R 100 )2], -OP(O)[N(R 100 )2], -NP(O)(R 100 )2, -NR100 P(O)(OR 100 )2, -N(R 100 )P(O)(OR 100 )[N(R 100 )2], -N(R 100 )P(O)[N(R 100 )2]2, or -NR 100 S(O)2R 100 and Each R 601 each independently represents an optionally substituted C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, or a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S; Each R 701 are independently hydrogen, deuterium, halogen, -CN, -OR 100 , -SR 100 , -S(O)R 100 , -S(O)2R 100 , -N(R 100 )2, -P(O)(OR 100 )2, -P(O)[N(R 100 )2](OR 100 ), -P(O)[N(R 100 )2]2, -Si(OH)2(R 100 )-, -Si(OH)(R 100 )2-, -Si(R 100 )3-, or an optionally substituted C1-C4 alkyl group; or R 701 and X 101 or X 301 form, together with the atoms connecting thereto, a 5- to 7-membered saturated or partially unsaturated carbocyclic ring or a heterocyclic ring containing 1 to 3 heteroatoms selected from boron, N, O, Si, or S; or two R on the same carbon 701 form, together with the atoms linked thereto, a 3- to 6-membered ring or a 4- to 7-membered heterocycle containing 1 to 2 heteroatoms selected from boron, N, O, Si, and S; or two R on adjacent carbons 701form, together with the atoms linked thereto, a 3- to 7-membered saturated or partially unsaturated carbocycle or a heterocycle containing 1 to 3 heteroatoms selected from boron, N, O, Si, or S, or form a saturated or partially unsaturated 7- to 13-membered bridged heterocycle or spiro heterocycle containing 1 to 3 heteroatoms selected from boron, N, O, Si, or S; ring D is each independently a 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S, a phenyl group, a 5- to 7-membered saturated or partially unsaturated cycloalkyl group, a 5- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 3 heteroatoms selected from N, O and S, or a 5-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S; L 101 is a bond or a C1-C4 alkylene group, and one or two methylene groups of the C1-C4 alkylene group are optionally selected from -O-, -C(O)-, -C(S)-, -C(R 100 )2-, -CH(R 100 )-, -C(F)2-, -N(R 100 )-, -S-, -S(O)2- or -CH=CH-; n'' is 0, 1, 2, 3 or 4; q'' is 0, 1, 2, 3 or 4.

[0274] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E6, E6a, E6b, E6c, E6d, E6e, E6f, E6g, E6h or E6i, [ka] Here, in the above E6, E6a, E6b, E6c, E6d, E6e, E6f, E6g, E6h or E6i, [ka] teeth, [ka] and Y is a bond, Y1, O, NH, NR2, C(O)O, C(O)NR2', Y1-O, Y1-NH, Y1-NR2, Y1-C(O), Y1-C(O)O, Y1-OC(O), Y1-C(O)NR2' or Y1-NR2'C(O), where Y1 is a C1-C6 alkylene group, a C2-C6 alkenyl group or a C2-C6 alkynyl group; X is C(O) or C(R3)2; X1-X2 is C(R3)=N or C(R3)2-C(R3)2, each R1 is independently a halogen, a nitro group, NH2, OH, C(O)OH, a C1-C6 alkyl group, or a C1-C6 alkoxy group; R2 is a C1-C6 alkyl group, a C2-C6 alkenyl group, a C3-C8 cycloalkyl group, a 3- to 8-membered heterocycloalkyl group, or a C(O)-3- to 8-membered heterocycloalkyl group, and R2 optionally contains one or more halogens, N(R a )2, NHC(O)R a , NHC(O)OR a , OR b , C3-C8 cycloalkyl group, 3-8 membered heterocycloalkyl group, C6-C 10 aryl group, or 5- to 10-membered heteroaryl group, where C3-C8 cycloalkyl group, 3- to 8-membered heterocycloalkyl group, C6-C 10 the aryl group or 5- to 10-membered heteroaryl group is optionally substituted with one or more halogen, NH, CN, nitro, OH, C(O)OH, C-C alkyl, C-C haloalkyl, C-C alkoxy or C-C haloalkoxy groups; R2' is H, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C3-C8 cycloalkyl group, or a 3- to 8-membered heterocycloalkyl group, and when R2' is not H, optionally one or more halogens, N(R a )2, NHC(O)R a , NHC(O)OR a , OR b, C3-C8 cycloalkyl group, 3-8 membered heterocycloalkyl group, C6-C 10 aryl group or 5-10 membered heteroaryl group, wherein C3-C8 cycloalkyl group, 3-8 membered heterocycloalkyl group, C6-C 10 The aryl group or 5- to 10-membered heteroaryl group may optionally be substituted with one or more other halogens, NH, CN, nitro, OH, C(O)OH, C-C alkyl groups, C-C haloalkyl groups, C-C alkoxy groups, or C-C haloalkoxy groups; Each R3 is independently H or a C1-C3 alkyl group, wherein the C1-C3 alkyl group is optionally a C6-C 10 substituted with an aryl group or a 5- to 10-membered heteroaryl group; each R3' is independently a C1-C3 alkyl group; each R4 is independently H or a C1-C3 alkyl group, or two R4 together with the carbon atoms connecting them form a C(O), a C3-C6 cycloalkyl group, or a 4-, 5-, or 6-membered heterocycloalkyl group containing one or two heteroatoms selected from N and O; R5 is H, a C1-C3 alkyl group, F, or Cl; Each R a are independently H or a C1-C6 alkyl group; R b is H or a tosyl group, t is 0 or 1, m is 0, 1, 2 or 3; n is 0, 1 or 2.

[0275] Ring A, X, X1, X2, Y 100 , R1, R3, R 3′ , R4, R5, t, m, and n are as defined in WO2017 / 007612 and US2018 / 0134684, the entire contents of which are incorporated herein by reference.

[0276] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E7, E7b, E7c, E7d or E7e, [ka] Here, in the above E7, E7b, E7c, E7d and E7e, W is CH2, CR a R b , C(S), C(O) or SO2; X is H, CH, O or S; Y is NH, an N-alkyl group, an N-aryl group, an N-heteroaryl group, an N-cycloalkyl group, an N-heterocycloalkyl group, O, or S; Z is H2, CH2, O or S, and in E7c, Z cannot simultaneously be H2; G and G' are each independently selected from hydrogen, a C1-C6 alkyl group, OH, a -CH2-heterocycloalkyl group optionally substituted with R', and a -CH2-phenyl group optionally substituted with R'; Q1, Q2, Q3, and Q4 are each independently carbon, nitrogen, or a nitrogen oxide; A is hydrogen, a C1-C6 alkyl group, a cycloalkyl group, or halogen; R, R a and R b are each independently hydrogen, a hydroxy group, a halogen atom, -NH2, or -N(C1-C6 alkyl). 1-2, C1-C6 alkyl group, C1-C6 alkoxy group, C1-C6 haloalkyl group, -CONR'R'', -OR', -NR'R'', -SR', -S02R', -S02NR'R'', -CR'R'', -CR'NR'R'', aryl group, heteroaryl group, C3-C8 cycloalkyl group, 3-8 membered heterocycloalkyl group, -P(O)(OR')R'', -P(O)R'R'', -OP(O)(OR')R'', -Cl, -F, -Br, -I, -CF3, -CN , -NR'SO2NR'R'', -NR'C(O)NR'R'', -C(O)NR'C(O)R'', -NR'C(=N-CN)NR'R'', -C(=N-CN)NR'R'', -NR'C(=N-CN)R'', -NR'C(=C-NO2)NR'R'', -SO2NR'COR'', -NO2, -COR', -C(C=N-OR')R'', -CR'=CR'R'', -CCR', -S(C=O)(C=N-R')R'', -SF5 or -OCF3, R' and R'' are each independently selected from a bond, hydrogen, a C1-C6 alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, or a heterocycloalkyl group; n'' is an integer from 1 to 4, ----- is a bond and may be the R stereoisomer, the S stereoisomer or no stereoisomer.

[0277] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] is.

[0278] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E8, E8a, E8b, E8c, E8d, E8e, E8f, E8g, E8h, E8i, E8j, E8k, E8l, E8m, E8n, E8o, E8p, E8q, E8s, E8t, E8u, E8v, E8w, E8x, E8y, E8z, E8aa, E8bb or E8cc, [ka] [ka] [ka] [ka] [ka] Here, in the above E8, E8a, E8b, E8c, E8d, E8e, E8f, E8g, E8h, E8i, E8j, E8k, E8l, E8m, E8n, E8o, E8p, E8q, E8s, E8t, E8u, E8v, E8w, E8x, E8y, E8z, E8aa, E8bb, or E8cc, each W is independently selected from CH, CHR, C(O), or SO; Q1, Q2, Q3, Q4, and Q5 are each independently carbon, N, or N substituted with R', or nitrogen oxide; R 1 is absent or is hydrogen, a hydroxy group, a cyano group, a C1-C3 alkyl group, or C(O), R 2 is absent or is hydrogen, a hydroxy group, a cyano group, a C1-C3 alkyl group, CHF2, CF3, CHO, or C(O)NH2, R 3 is selected from hydrogen, an alkyl group (e.g., a C1-C6 alkyl group or a C1-C3 alkyl group), an optionally substituted alkyl group (e.g., a C1-C6 alkyl group or a C1-C3 alkyl group), an alkoxy group (e.g., a C1-C6 alkoxy group or a C1-C3 alkoxy group), and an optionally substituted alkoxy group (e.g., a C1-C6 alkoxy group or a C1-C3 alkoxy group); R 4 is selected from hydrogen, an alkyl group, or an optionally substituted alkyl group; R 5 or R 6 are each independently selected from hydrogen, halogen, C(O)R', a cyano group, a hydroxy group, and CF3; X is carbon, nitrogen or C(O); X1 is carbon, nitrogen or C(O); R' is hydrogen, halogen, amine, alkyl group (e.g., C1-C3 alkyl group), optionally substituted alkyl group (e.g., C1-C3 alkyl group), alkoxy group (e.g., C1-C3 alkoxy group), optionally substituted alkoxy group (e.g., C1-C3 alkoxy group), NR 2 R 3 , C(O)OR 2 , an optionally substituted phenyl group; R is H, OH, a lower alkyl group, a lower alkoxy group, a cyano group, a halo lower alkoxy group, or a halo lower alkyl group; n is 0, 1, 2, 3 or 4; [ka] is a single bond or a double bond.

[0279] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E9a, E9b, E9c, E9d, E9e, E9f, E9g, E9h, E9i, E9j, E9k, E9l, E9m, E9n, E9o, E9p, E9q, E9r or E9s, [ka] [ka] Here, in the above E9a, E9b, E9c, E9d, E9e, E9f, E9g, E9h, E9i, E9j, E9k, E9l, E9m, E9n, E9o, E9p, E9q, E9r or E9s, W is independently selected from CH, CHR, C=O, SO, NH, and an N-alkyl group; R 1 is selected from H, CN, and C1-C3 alkyl groups; R 2 is H or a C1-C3 alkyl group, R 4 is a methyl group or an ethyl group, R 5 is H or a halogen, R 6 is H or a halogen, R is H, R' is H, Q1 and Q2 are each independently H or C or N substituted with a group independently selected from C1-C3 alkyl groups; [ka] It is a single bond or a double bond.

[0280] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E10, E10a or E10b, [ka] Here, in the above E10, E10a or E10b, the above X A is C(O) or C(R 3A )2, Z is NR 3A or CR 3A and Each R 1A are each independently a halogen, a hydroxy group, a —C1-C6 alkyl group, or a C1-C6 alkoxy group, Each R 3A are each independently hydrogen or a C1-C3 alkyl group; R 3’ are each independently a C1-C3 alkyl group, Each R 4A are each independently hydrogen or a C1-C3 alkyl group, or two R 4A together with the carbon atoms to which they are attached form a C(O), a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6-membered heterocycloalkyl group containing one or two heteroatoms selected from N or O; R 5A is selected from hydrogen, a C1-C3 alkyl group, or a halogen; Each R 6A are each independently hydrogen or a C1-C3 alkyl group, or two R 6A together with the carbon atoms to which they are attached form a C(O), a C3-C6 cycloalkyl group, or a 3-, 4-, 5- or 6-membered heterocycloalkyl group containing one or two heteroatoms selected from N or O; m is 0, 1, 2 or 3; n is 0, 1 or 2; a1 is 0 or 1.

[0281] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E11, [ka] Here, in the above E11, -X1-X2- is -C(R 3A )=N- or -C(R 3A )2-C(R 3A )2- and Each R 1A are each independently a halogen, a hydroxy group, a C1-C6 alkyl group, or a C1-C6 alkoxy group, R 3A is hydrogen or a C1-C3 alkyl group, R 3’ are each independently a C1-C3 alkyl group, R 4A is hydrogen or a C1-C3 alkyl group, or two R 4A together with the carbon atoms to which they are attached form a C(O), a C3-C6 cycloalkyl group, or a 4-, 5- or 6-membered heterocycloalkyl group containing one or two heteroatoms selected from N or O; m is 0, 1, 2 or 3; n is 0, 1 or 2; a1 is 0 or 1.

[0282] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E12, [ka] Here, in the above E12, Each R 2’ are each independently a halogen, a hydroxy group, a C1-C6 alkyl group, or a C1-C6 alkoxy group, Each R 4’are each independently a halogen, a hydroxy group, a C1-C6 alkyl group, or a C1-C6 alkoxy group, Each R 5’ are each independently a halogen, a hydroxy group, a C1-C6 alkyl group, or a C1-C6 alkoxy group, n1 is 0, 1, 2, 3, 4, 5 or 6; n2 is 0, 1, 2, 3 or 4; n3 is 0, 1 or 2.

[0283] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E13, [ka] Here, in the above E13, R 3A is hydrogen or a C1-C3 alkyl group, Each R 3’ is a C1-C3 alkyl group, Each R 6’ are each independently a halogen, a hydroxy group, a C1-C6 alkyl group, or a C1-C6 alkoxy group, n1 is 0, 1, 2, 3, 4 or 5; m1 is 0, 1, 2, 3, 4 or 5.

[0284] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E14, E14a, E14b, E14c, E14d or E14e, [ka] Here, in the above E14, E14a, E14b, E14c, E14d and E14e, Ar is an aryl group, a cycloalkyl group, a heterocycloalkyl group, or a heteroaryl group; L is absent or -SO2, -SO2R', -SO2R'R'', -SO2NR'R'', -SO2NR'R''C(=O), -NR'S02R'', -R'SO2NR'R''', -C(=O), -C(=O)R', -OC(=O)R', -C(=O)NR'R'', -NR'C(=O)R'', -NR'C(=O), R''C(=O), -OR', -NR'R'', -SR', -N3-C(=O)OR', -O(CR'R'') r C(=O)R', -O(CR'R'') r NR''C(=O)R', -O(CR'R'') r NR″S02R′, —OC(═O)NR′R′, —NR′C(═O)OR″ or an optionally substituted C1-C6 alkyl group; R', R'', and R''' are each independently selected from H, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted ether group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted arylalkyl group, a substituted or unsubstituted heteroalkyl group, a substituted or unsubstituted alkylated acylaryl group, or a substituted or unsubstituted amine; r is an integer from 1 to 6; R 1 , R 2 , R 3are each independently selected from H, a halogen, a hydroxy group, an azide group, an alkoxy group, a mercapto group, an imino group, an amino group, a phosphonate, a phosphate, a carbonyl group, a carboxy group, a cyano group, a silyl group, an ether, an alkylthio group, a sulfonyl group, a sulfonylamino group, a ketone, an aldehyde, a substituted or unsubstituted amine, a substituted or unsubstituted amide, a nitro group, an ester, a morpholinyl group, a dioxolane, a substituted or unsubstituted alkyl group, a substituted or unsubstituted haloalkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted arylalkyl group, a substituted or unsubstituted heteroarylalkyl group, a substituted or unsubstituted alkylheteroaryl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocycloalkyl group, or a combination thereof; or R 1 , R 2 are bonded to form a 5- to 7-membered heterocycle, and R 1 , R 2 are bonded to form a 5- to 7-membered heterocycle, Ar and the 5- to 7-membered heterocycle do not form a bonded ring but form a substituent of the 5- to 7-membered heterocycle, R 4 , R 5 is a hydrogen, a halogen, a hydroxy group, an azide, an ether, an alkoxy group, a mercapto group, an alkylthio group, a sulfonyl group, a sulfonamide, a ketone, an aldehyde, an ester, a substituted or unsubstituted alkyl group, a substituted or unsubstituted haloalkyl group, a substituted or unsubstituted arylalkyl group, a substituted or unsubstituted enone group, an unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a heterocyclyl group, or a combination thereof; R 8is hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted haloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a heterocyclyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted alkylaryl group, or a combination thereof; [ka] is a single or double bond, x is 0, 1 or 2; y is an integer of 1 to 6;

[0285] In some embodiments, in the above E14, E14a, E14b, E14c, E14d, and E14e, Ar, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , A, L, x, y and [ka] is as defined and explained in WO2017 / 161119, the entire text of which is incorporated herein by reference.

[0286] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E15, E15a, E15b, E15c, E15d, E15e, E15f, E15g or E15h, [ka] Here, in the above E15, E15a, E15b, E15c, E15d, E15e, E15f, E15g and E15h, Ring B is an aryl group, a heteroaryl group, a cycloalkyl group, or a heterocycloalkyl group; L 101 is a bond or a C1-C6 alkyl group, A is C, S, a substituted or unsubstituted C1-C8 alkyl group or a combination thereof; G 100 is C, S, N, a substituted or unsubstituted C1-C8 alkyl group or a combination thereof; R 101 , R 201 and R 301 are each selected from hydrogen, halogen, hydroxy, azide, alkoxy, mercapto, imino, amido, phosphonate, phosphinate, carbonyl, carboxy, cyano, silyl, ether, alkylthio, sulfonyl, sulfonylamino, ketone, aldehyde, substituted or unsubstituted amine, substituted or unsubstituted amide, nitro, ester, morpholino, dioxolane, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkylheteroaryl, and combinations thereof; or wherein R 101 and R 201 are joined to form a 5- to 7-membered heterocycloalkyl group, where R 101 and R 201 are bonded to form a 5- to 7-membered heterocycle, ring B is optionally not fused with the 5- to 7-membered heterocycle but is a substituent of the 5- to 7-membered heterocycle, R 401 and R 501are each selected from hydrogen, halogen, a hydroxy group, an azide, an ether, an alkoxy group, a mercapto group, an alkylthio group, a sulfonyl group, a sulfonylamino group, a ketone, an aldehyde, an ester, a substituted or unsubstituted alkyl group, a substituted or unsubstituted haloalkyl group, a substituted or unsubstituted arylalkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a heterocycloalkyl group, and combinations thereof; R 601 and R 701 are each independently oxo, hydrogen, a C1-C8 alkyl group, or R 601 and R 701 combines to form oxo, R 801 is selected from hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted arylalkyl groups, substituted or unsubstituted alkenyl groups, substituted or unsubstituted alkynyl groups, substituted or unsubstituted cycloalkyl groups, heterocycloalkyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted alkylaryl groups, and combinations thereof; x″ and y″ are each independently 0, 1, or 2; [ka] is a single or double bond, In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E16, E16a or E16b, [ka] Here, in E16, E16a and E16b above, W 101 is CR 601 R 701, C(O), C(S), C=CH2, SO2, S(O), P(O)O alkyl group, P(O)NH alkyl group, P(O)N(alkyl)2, P(O) alkyl group, P(O)OH, P(O)NH2; W 201 is CR 801 R 901 , C(O), C(S), C=CH2, SO2, S(O), P(O)O alkyl group, P(O)NH alkyl group, P(O)N(alkyl)2, P(O) alkyl group, P(O)OH, P(O)NH2; X 100 are independently NH, NR 301 , CH2, CHR 301 , C(R 301 ) 2, O or S; n'' is 0, 1, 2 or 3; [ka] is a single or double bond, where [ka] is a single bond, n'' is 0, 1, 2 or 3; [ka] is a double bond, n'' is 0, 1 or 2; R 101 teeth, [ka] [ka] [ka] or R 101* Selected from R 201 is an alkyl group, hydrogen, a heteroalkyl group, an aryl group, a heteroaryl group, or a heterocycloalkyl group, Or R 101 and R 201are joined to form a 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycloalkyl or heteroaryl group, said heterocycloalkyl or heteroaryl group optionally being selected from the group consisting of R 501 , R 120 and is substituted with one or more substituents selected from R 101* is chosen from: [ka] R 301 is selected from alkyl groups, -C(O)H, C(O)OH, -C(O)alkyl groups, -C(O)Oalkyl groups, alkenyl groups, alkynyl groups, aryl groups, heteroaryl groups or heteroalkyl groups, R 401 is selected from alkyl groups, alkenyl groups, alkynyl groups, halogens, hydroxy groups, alkoxy groups, azido groups, amino groups, cyano groups, -NH(alkyl), -N(alkyl)2, -NHS(O)2(alkyl), -N(alkyl)SO2alkyl groups, -NHSO2(aryl, heteroaryl or heterocycloalkyl), -N(alkyl)SO2(aryl, heteroaryl or heterocycloalkyl), -NHSO2(alkenyl), -N(alkyl)SO2(alkenyl), -NHSO2(alkynyl), -N(alkyl)SO2(alkynyl) or haloalkyl groups, aryl groups, heteroaryl groups, heteroalkyl groups and cycloalkyl groups; Or two R's 401 form a 3-, 4-, 5- or 6-membered ring together with the carbon atoms to which they are attached, R 501 and R 140are each independently selected from hydrogen, alkyl groups, alkenyl groups, alkynyl groups, halogen, hydroxy groups, alkoxy groups, azido groups, amino groups, cyano groups, -NH(alkyl), -N(alkyl), -NHS(O)(alkyl), -N(alkyl)SO(alkyl), -NHSO(aryl, heteroaryl or heterocycloalkyl), -N(alkyl)SO(aryl, heteroaryl or heterocycloalkyl), -NHSO(alkenyl), -N(alkyl)SO(alkenyl), -NHSO(alkynyl), -N(alkyl)SO(alkynyl) or haloalkyl groups, aryl groups, heteroaryl groups, heteroalkyl groups and cycloalkyl groups; Or R 501 are independently C(O)R 401 , a cyano group, an aryl group, an aryloxy group, a heterocycloalkyl group, a heteroaryl group, an arylalkyl group, an alkoxy group, a hydroxy group, an O-arylalkyl group or a cycloalkyl group; R 601 , R 701 , R 801 , R 901 , R 1001 , or R 110 are independently selected from hydrogen, alkyl groups, heteroalkyl groups, hydroxy groups, alkoxy groups, amines, -NH(alkyl) and -N(alkyl)2; Or R 601 and R 701 form a 3-, 4-, 5-, or 6-membered spirocarbocyclic ring together with the carbon atoms to which they are attached, or form a 4-, 5-, or 6-membered spiroheterocyclic ring containing one or two heteroatoms selected from N and O; Or R 801 and R 901 form a 3-, 4-, 5-, or 6-membered spirocarbocyclic ring together with the carbon atoms to which they are attached, or form a 4-, 5-, or 6-membered spiroheterocyclic ring containing one or two heteroatoms selected from N and O; Or R 1001 and R 110form a 3-, 4-, 5-, or 6-membered spirocarbocyclic ring together with the carbon atoms to which they are attached, or form a 4-, 5-, or 6-membered spiroheterocyclic ring containing one or two heteroatoms selected from N and O; Or R 601 and R 801 together form one or two bridged carbocyclic rings, Or R 601 and R 1001 together form one or two bridged carbocyclic rings, Or R 801 and R 1001 together form one or two bridged carbocyclic rings, Or R 601 and R 140 together form 3, 4, 5 or 6 fused carbocyclic rings, Or R 140 and R 1001 together form 3, 4, 5 or 6 fused carbocyclic rings, Or R 801 and R 140 together form one or two bridged carbocyclic rings, Or R 401 and R 140 together form 3, 4, 5 or 6 fused carbocyclic rings, wherein the R 501 is R 140 located at the α-carbon or together form 1, 2, 3 or 4 bridged carbocyclic rings, wherein R 501 is R 140 Not located at the α carbon, R 120 is L 100 and R 170 teeth, [ka] Selected from Y 100 is N, CH or CR 101 where 0, 1, 2 or 3 Y 100 is N, R 101are independently selected from hydrogen, alkyl groups, alkenyl groups, alkynyl groups, haloalkyl groups, alkoxy groups, hydroxy groups, aryl groups, heteroaryl groups, heterocycloalkyl groups, arylalkyl groups, heteroarylalkyl groups, heterocycloalkyl groups, aryloxy groups, heteroaryloxy groups, CN, —C(O)Oalkyl groups, —C(O)OH, NO, F, Cl, Br, I, CF, NH, NH(alkyl), N(alkyl), or heteroalkyl groups.

[0287] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E17, E17a, E17b or E17c, [ka] Here, in E17, E17a, E17b and E17c above, W1 is CR6R7, C=O, C=S, C=CH2, SO2, S(O), P(O)Oalkyl group, P(O)NHalkyl group, P(O)N(alkyl)2, P(O)alkyl group, P(O)OH or P(O)H2; W2 is CR8R9, C=O, C=S, C=CH2, SO2, S(O), P(O)Oalkyl group, P(O)NHalkyl group, P(O)N(alkyl)2, P(O)alkyl group, P(O)OH or P(O)H2; X and X1 each independently represent NH or NR 3 , CH2, CHR 3 , C(R 3 ) 2, O or S; n'' is 0, 1, 2 or 3; [ka] is a single or double bond, and [ka] is a single bond, n'' is 0, 1, 2 or 3; [ka] is a double bond, n'' is 0, 1 or 2; R1 is [ka] or R 1* wherein X is O or N, and when X is O oxygen, R2 is absent; Ring A is a phenyl group, a 5- to 6-membered heteroaryl group, a 3- to 6-membered cycloalkyl group, or a 4- to 6-membered heterocycloalkyl group, and the phenyl group, the 5- to 6-membered heteroaryl group, the 3- to 6-membered cycloalkyl group, or the 4- to 6-membered heterocycloalkyl group may optionally be R 12 is replaced by Ring B is absent, a phenyl group, or a 5- to 6-membered heteroaryl group, and the phenyl group or the 5- to 6-membered heteroaryl group is optionally R5 or R 12 is replaced by R2 is an alkyl group, H, an aliphatic group, a heteroaliphatic group, an aryl group, a heteroaryl group, or a heterocycloalkyl group; R 1* is an optionally substituted aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkylamino, alkoxy, ester, sulfonyl, or amide group; R3 is an alkyl group, —C(O)H, —C(O)OH, —C(O)alkyl group, —C(O)Oalkyl group, alkenyl group, or alkynyl group; R4 is an alkyl group, an alkenyl group, an alkynyl group, a halogen atom, a hydroxy group, an alkoxy group, an azido group, an amino group, an -NH alkyl group, an -N(alkyl)2, an -NHSO2 alkyl group, an -N(alkyl)SO2 alkyl group, an -NHSO2 aryl group, an -N(alkyl)SO2 aryl group, an -NHSO2 alkenyl group, an -N(alkyl)SO2 alkenyl group, an -NHSO2 alkynyl group, an -N(alkyl)SO2 alkynyl group, or a haloalkane; or two R4 together with the C atom to which they are attached form a 3-, 4-, 5- or 6-membered ring, R6, R7, R8, R9, R 10 and R 11 are independently selected from hydrogen, alkyl groups, aliphatic groups, heteroaliphatic groups, hydroxy groups, alkoxy groups, amines, -NH(aliphatic groups containing alkyl groups), and -N(aliphatic groups containing alkyl groups); or R6 and R7 together with the carbon atoms to which they are attached form a 3-, 4-, 5- or 6-membered spirocarbocyclic ring or a 4-, 5- or 6-membered spiroheterocyclic ring, wherein the heteroatom is one or two N or O; or R8 and R9 together with the carbon atoms to which they are attached form a 3-, 4-, 5- or 6-membered spirocarbocyclic ring or a 4-, 5- or 6-membered spiroheterocyclic ring, wherein the heteroatom is one or two N or O; Or R 10 , R 11 together with the carbon atoms to which they are attached form a 3-, 4-, 5- or 6-membered spirocarbocyclic ring or a 4-, 5- or 6-membered spiroheterocyclic ring, said heteroatoms being 1 or 2 N or O; or R6 and R8 form one or two bridged carbocyclic rings; Or R6, R 10 forms one or two bridged carbocyclic rings, Or R8, R 10 forms one or two bridged carbocyclic rings, Or R 14 , R6 forms 3, 4, 5 or 6 fused carbocyclic rings; Or R 14 , R 10 forms 3, 4, 5 or 6 fused carbocyclic rings, Or R 14 , R8 forms one or two bridged carbocyclic rings; Or R 14 , R4 forms 3, 4, 5 or 6 fused carbocyclic rings, and R4 is R 14 or form 1, 2, 3 or 4 bridged carbocyclic rings, and R4 is 14 is not located at the carbon α connected to R 12is the chain that connects to the target ligand, R5, R 14 are each selected from hydrogen, an alkyl group, an alkene, an alkyne, a halogen, a hydroxy group, an alkoxy group, an azide group, an amino group, a cyano group, -NH(aliphatic containing an alkyl group), -N(aliphatic containing an alkyl group)2, -NHSO2(aliphatic containing an alkyl group), -N(aliphatic containing an alkyl group)SO2alkyl group, -NHSO2(aryl group, heteroaryl group or heterocycle), C(O)R4, -N(alkyl)SO2(aryl group, heteroaryl group or heterocycle), -NHSO2alkenyl group, -N(alkyl)SO2alkenyl group, -NHSO2alkynyl group, -N(alkyl)SO2alkynyl group, haloalkyl group, aliphatic, heteroaliphatic, aryl group, heteroaryl group, heteroalkyl group and carbocycle; wherein each R5 is optionally substituted with one or more groups selected from alkyl groups, alkenes, alkynes, halogens, hydroxy groups, alkoxy groups, azido groups, amino groups, -NH alkyl groups, -N(alkyl)2, aryl groups, heterocycloalkyl groups, heteroaryl groups, haloalkyl groups, and cycloalkyl groups; R 16 teeth, [ka] is.

[0288] In some embodiments, in E17, E17a, E17b, and E17c, R, R, R 10 , R 11 , R 14 , R 16 ,W1,W2,X, [ka] and n'' are as defined in WO2018 / 237026, the entire contents of which are incorporated herein by reference.

[0289] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E18, E18a, E18b, E18c, E18d, E18e, E18f, E18g, E18h, E18i, E18j, E18k, E18l or E18m, [ka] [ka] [ka] Here, in the above E18, E18a, E18b, E18c, E18d, E18e, E18f, E18g, E18h, E18i, E18j, E18k, E18l and E18m, X 1 -C(R)2, -O-, -NR-, -CF2-, [ka] , —C(O)—, —C(S)— or [ka] and X 2 and X 3 are each independently -CH2-, -C(O)-, -C(S)-, -C(R)2C(O)- or [ka] and Z 1 and Z 2 are each independently a carbon atom or a nitrogen atom, Ring A x is selected from a phenyl group, a 4- to 6-membered saturated or partially unsaturated cycloalkyl group or a heterocycloalkyl group containing 1 to 3 heteroatoms selected from N, O, and S, and a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S; L x represents a bond or a C1-C3 alkylene group, in which 1 to 2 methylene groups are optionally substituted by a group selected from -O-, -S-, -C(O)-, -C(S)-, -C(R)2-, -CRF, -CF2-, -NR-, -S(O)2-, -CH=CH- or an alkynylene group; R x is hydrogen, deuterium, -R z , halogen, -CN, -NO2, -OR, -SR, -N(R)2, -S(O)R, -S(O)2R, -S(O)2N(R)2, -CF(R)2-, -CF2R-, -CF3-, -C(R)2(OR)-, -C(R)2[ N(R)2]-, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)N(R)OR, -OC(O)R, -OC(O)N(R)2, -C(S)NR2, -NRC(O)OR, -NRC(O)R, -NRC( -O)N(R)2, -NRS(O)2R, -C(R)2N(R)C(O)R, -C(R)2N(R)C(O)N(R)2, -OP(O)(R)2, -OP(O)(OR)2, -OP(O)(OR)[N(R)2], -OP(O)[N(R)2], -NP(O)(R)2, -NRP(O)(OR)2, -N(R)P(O)(OR)[N(R)2], -N(R)P(O)[N(R)2]2, -Si(OR)R2 or -SiR3; The Two R's x together with the atoms to which they are connected form an optionally substituted 5-8 membered partially unsaturated or aryl-fused heterocycloalkyl group containing 0-2 heteroatoms selected from N, O, or S; each R is independently hydrogen, an optionally substituted C1-C6 alkyl group, a phenyl group, a 4-7 membered saturated or partially unsaturated heterocycloalkyl group containing 1-2 heteroatoms selected from N, O, or S, or a 5-6 membered heteroaryl ring containing 1-4 heteroatoms selected from N, O, or S; two Rs on the same carbon atom or the same nitrogen atom together with the atom connecting them form an optionally substituted 4- to 7-membered saturated or partially unsaturated cycloalkyl or heterocycloalkyl group, or a heteroaryl group containing 1 to 4 heteroatoms selected from N, O and S; R y is hydrogen or [ka] Selected from Ring B x is selected from a phenyl group, a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic cycloalkyl group, a heterocycloalkyl group containing 1 to 3 heteroatoms selected from N, O, and S, or a 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, and S, and the ring B x is further optionally substituted with 1 to 2 oxo groups; Each R w are independently hydrogen, deuterium, and R z , halogen, -CN, -NO2, -OR, -SR, -N(R)2, -S(O)R, -S(O)2R, -S(O)2N(R)2, -CF(R)2-, -CF2R-, -CF3-, -C(R)2(OR)-, -C(R)2 [N(R)2]-, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)N(R)OR, -OC(O)R, -OC(O)N(R)2, -C(S)NR2, -NRC(O)OR, -NRC(O)R, -NR C(O)N(R)2, -NRS(O)2R, -C(R)2N(R)C(O)R, -C(R)2N(R)C(O)N(R)2, -OP(O)(R)2, -OP(O)(OR)2, -OP(O)(OR)[N(R)2], - selected from OP(O)[N(R)2], -NP(O)(R)2, -NRP(O)(OR)2, -N(R)P(O)(OR)[N(R)2], -N(R)P(O)[N(R)2]2, -Si(OR)R2 or -SiR3, Each R zare each independently a C1-C6 alkyl group, a phenyl group, a 4- to 7-membered saturated or partially unsaturated heterocycloalkyl group containing 1 to 2 heteroatoms selected from N, O, or S, or a 5- to 6-membered heteroaryl ring containing 1 to 4 heteroatoms selected from N, O, and S; x is 0, 1, 2, 3 or 4; y is 0, 1 or 2; w is 0, 1, 2, 3 or 4.

[0290] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E19, E19a, E19b, E19c, E19d, E19e, E19f, E19g, E19h or E19i, [ka] Here, in the above E19, E19a, E19b, E19c, E19d, E19e, E19f, E19g, E19h and E19i, A 1 is -C(R 16a )= or -N=, A 2 is -C(R 16b )= or -N=, A 3 is -C(R 16c )= or -N=, G is -C(R 16d )= or -N=, Z is —CH or —C(═O)—; R 5 is H, a methyl group or F, R 16a , R 16b , R 16c and R 16d are each independently selected from H, halogen, or a C1-C4 alkyl group.

[0291] In some embodiments, in E19, E19a, E19b, E19c, E19d, E19e, E19f, E19g, E19h, and E19i, A 1 , A 2 , A 3 , Z, G and R 5 is as defined and explained in WO2017 / 176958, the entire text of which is incorporated herein by reference.

[0292] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E20, E20a, E20b, E20c, E20d, E20e or E20f, [ka] Here, in the above E20, E20a, E20b, E20c, E20d, E20e and E20f, L 1 is a bond, [ka] Selected from X 1 , X 2 , X 3 and X 4 are each independently nitrogen or CR 4 Selected from and X 1 , X 2 , X 3 and X 4 In which at most two are simultaneously selected from nitrogen, Z 2 and Z 3 is selected from —CH— or —C(O)—, and Z 1 and Z 2 wherein at least one is selected from —C(O)—; o is selected from 0, 1, 2, 3 or 4; Each R 4are each independently selected from hydrogen, halogen, a hydroxy group, a C1-C6 alkyl group, a C1-C6 alkoxy group, or a C1-C6 haloalkyl group; Each R 5 are each independently selected from hydrogen, a C1-C6 alkyl group, or a -C(O)-alkyl group; Each R 8 are each independently selected from hydrogen, a C1-C6 alkyl group, or a C1-C6 haloalkyl group, or two R 8 together with the atom to which they are attached form a cyclopropyl group.

[0293] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E21, [ka] Here, in the above E21, X'' is C or N; Y″ is C, N, O or S; Q1, Q2, Q3, Q4, and Q5 are each independently CR3″ or N; R3'' is independently hydrogen, deuterium, a hydroxy group, an amino group, a cyano group, a halogen, a C1-C6 alkyl group, a C3-C8 cycloalkyl group, a 3- to 8-membered heterocycloalkyl group (e.g., a morpholinyl group, e.g., [ka] ), 6- to 10-membered aryl group, 5- to 10-membered heteroaryl group, -O(C1-C6 alkyl), -O-(C3-C8 cycloalkyl), -O-(3- to 8-membered heterocycloalkyl), N(C1-C6 alkyl)1-2, NH(C3-C8 cycloalkyl), NH(3- to 8-membered heterocycloalkyl), -O-(C6-C 10-O-(aryl), -O-(5- to 10-membered heteroaryl), wherein the alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group, and heteroaryl group are optionally and independently substituted with 1 to 3 groups selected from a hydroxy group, a halogen atom, a cyano group, and an amino group; m'' is 1, 2 or 3; R1" each independently represents hydrogen, deuterium, a hydroxy group, an amino group, a cyano group, a halogen atom, a C1-C6 alkyl group, a C3-C8 cycloalkyl group, a 3- to 8-membered heterocycloalkyl group, a 6- to 10-membered aryl group, a 5- to 10-membered heteroaryl group, or -O(C1-C6 alkyl), and the alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group, and heteroaryl group are optionally and independently substituted with 1 to 3 groups selected from a hydroxy group, a halogen atom, a cyano group, and an amino group; R2'' is hydrogen, deuterium, a C1-C6 alkyl group, or a C3-C6 cycloalkyl group, and the C1-C6 alkyl group and the C3-C6 cycloalkyl group are optionally and independently substituted with 1 to 3 groups selected from a hydroxy group, a halogen, a cyano group, and an amino group.

[0294] In a specific embodiment of the present invention, one or two of Q1, Q2, Q3, Q4, and Q5 in the above E21 are N, and the remaining are each independently CR3''.

[0295] In a specific embodiment of the present invention, Q1, Q2, Q3, Q4, and Q5 in the above E21 are each independently CR3''.

[0296] In a particular embodiment of the present invention, X'' in E21 above is N.

[0297] In a particular embodiment of the present invention, X'' in E21 above is C.

[0298] In a particular embodiment of the present invention, Y'' in E21 above is N.

[0299] In certain embodiments of the present invention, R1" in E21 above is independently hydrogen, deuterium, -F, -Cl, or a C1-C6 alkyl group, wherein the alkyl group is optionally substituted with 1 to 3 halogens, and preferably R1" is hydrogen.

[0300] In certain embodiments of the present invention, R2'' in the above E21 is hydrogen or a C1-C6 alkyl group, the alkyl group being optionally substituted with 1 to 3 halogens, preferably R2'' is hydrogen.

[0301] In certain embodiments of the present invention, R3" in E21 above is independently hydrogen, deuterium, halogen, -O(C1-C6 alkyl), or a C1-C6 alkyl group, wherein the alkyl group is optionally substituted with 1 to 3 halogens; preferably, R3" is independently hydrogen, deuterium, F, Cl, a methyl group, a methoxy group, an ethoxy group, a trifluoromethoxy group, a 2-hydroxypropan-2yl group, or a trifluoromethyl group.

[0302] In a particular embodiment of the present invention, m in E21 above is 2.

[0303] In certain embodiments of the invention, E21 has the structure: [ka] Here, Q1, Q2, Q3, Q4, Q5, R1'', R2'', and m'' are as defined in E21 above.

[0304] In certain embodiments of the invention, E21 has the structure: [ka] Here, R1'', R2'', R3'', and m'' are as defined in E21 above.

[0305] In certain embodiments of the invention, E21 has the structure: [ka] wherein R1", R2", and R3" are as defined in E21. In certain embodiments of the present invention, E21 has the structure of the following formula: [ka] wherein R3" is as defined in E21. In certain embodiments of the invention, E21 has the structure: [ka] Here, Q1, Q2, Q3, Q5, R1'', R2'', and m'' are as defined in E21 above.

[0306] In certain embodiments of the invention, E21 has the structure: [ka] Here, R1'', R2'', R3'', and m'' are as defined in E21 above.

[0307] In certain embodiments of the invention, E21 has the structure: [ka] Here, R1'', R2'', and R3'' are as defined in E21-1 above.

[0308] In certain embodiments of the invention, E21 has the structure: [ka] wherein R3'' is as defined in E21 above.

[0309] In certain embodiments of the invention, E21 has the structure: [ka] wherein R3'' is as defined in E21 above.

[0310] In certain embodiments of the invention, E21 has the structure: [ka] wherein R3'' is as defined in E21 above.

[0311] In certain embodiments of the present invention, in the above E21 and E21-1a to 1j, R3" is hydrogen, halogen (e.g., F or Cl), a C1-C6 alkyl group or -O(C1-C6 alkyl) (e.g., -OCH3), and the above C1-C6 alkyl group and -O(C1-C6 alkyl) are optionally substituted with 1 to 3 halogens (e.g., F).

[0312] In certain embodiments of the present invention, in the above E21 and E21-1a to 1j, R3'' is hydrogen, F, Cl, CF3, -OCF3, or -OCH3.

[0313] In certain preferred embodiments of the invention, E21-1h above, R3'' is halogen (eg, F or Cl) or -O(C1-C6 alkyl) (eg, -OCH3).

[0314] In certain embodiments of the invention, E21-1h has any one of the following structures: [ka]

[0315] In certain preferred embodiments of the invention, E21-1h has any one of the following structures: [ka]

[0316] In certain embodiments of the present invention, E21-1i has the following structure: [ka]

[0317] In certain embodiments of the invention, E21-1j has any one of the following structures: [ka]

[0318] In certain embodiments of the invention, E21 is [ka] Selected from.

[0319] In certain embodiments of the invention, E21 is [ka] Selected from.

[0320] In certain preferred embodiments of the present invention, E21 has the structure of the following formula: [ka]

[0321] In certain preferred embodiments of the present invention, E21 has the structure of the following formula: [ka]

[0322] In certain preferred embodiments of the present invention, E21 has the structure of the following formula: [ka]

[0323] In certain preferred embodiments of the present invention, E21 has the structure of the following formula: [ka]

[0324] In certain preferred embodiments of the present invention, E21 has the structure of the following formula: [ka]

[0325] In certain embodiments of the invention, E21 has the structure: [ka] Here, Q1, Q2, Q3, Q4, Q5, R1'', R2'', and m'' are as defined in E21 above.

[0326] In certain embodiments of the invention, E21 has the structure: [ka] Here, R1'', R2'', R3'', and m'' are as defined in E21 above.

[0327] In certain embodiments of the invention, E21 has the structure: [ka] Here, R1'', R2'', and R3'' are as defined in E21 above.

[0328] In certain embodiments of the invention, E21 has the structure: [ka] wherein R3'' is as defined in E21 above.

[0329] In certain embodiments of the invention, E21 has the structure: [ka] Here, Q1, Q2, Q3, Q5, R1'', R2'', and m'' are as defined in E21 above.

[0330] In certain embodiments of the invention, E21 has the structure: [ka] Here, R1'', R2'', R3'', and m'' are as defined in E21-1 above.

[0331] In certain embodiments of the invention, E21 has the structure: [ka] Here, R1'', R2'', and R3'' are as defined in E21 above.

[0332] In certain embodiments of the invention, E21 has the structure: [ka] wherein R3'' is as defined in E21 above.

[0333] In certain embodiments of the invention, E21 is [ka] Selected from.

[0334] In certain embodiments of the invention, E21 is [ka] Selected from.

[0335] Preferably, in certain embodiments of the invention, E21 has any one of the following structures: [ka]

[0336] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E22, [ka] or a pharmaceutically acceptable salt thereof, wherein in the above E22: R 1′ is an optionally substituted C1-C6 alkyl group, optionally substituted -(CH2) n OH, optionally substituted -(CH) n SH, optionally substituted -(CH) n -O-(C1-C6 alkyl), optionally substituted -(CH2) n -WC(O)CW-(C0-C6 alkyl), where each W is independently hydrogen or a C1-C3 alkyl group, optionally substituted -(CH2) n C(O)OH, optionally substituted —(CH) n C(O)—(C1-C6 alkyl), optionally substituted —(CH2) n NHC(O)-R1, optionally substituted -(CH2) n C(O)—NR1R2, optionally substituted —(CH2) n OC(O)-NR1R2, -(CHO) n H, optionally substituted -(CH) n OC(O)—(C1-C6 alkyl), optionally substituted —(CHO) nC(O)OH, optionally substituted -(OCH2) n O—(C1-C6 alkyl), optionally substituted —(CHO) n C(O)—(C1-C6 alkyl), optionally substituted —(CHO) n C(O)-NR1R2, -(CH2CH2O) n H, optionally substituted -(CH2CH2O) n COOH, optionally substituted -(OCH2CH2) n O—(C1-C6 alkyl), optionally substituted —(OCH2CH2) n C(O)-NR1R2, optionally substituted -S(O)2R s , optionally substituted S(O)R s , a nitro group, a cyano group, or a halogen (F, Cl, Br, or I, preferably F or Cl), R1 and R2 are each independently hydrogen or a C1-C6 alkyl group, the alkyl group optionally substituted with one or two hydroxy groups or one, two or three halogens (preferably F); R S is a C1-C6 alkyl group, an optionally substituted aryl group, a heteroaryl group, or a heterocycloalkyl group, or -(CH2) m NR1R2, X and X' are each independently C(O), C(S), S(O), or S(O) (preferably, X and X' are both C(O)); R 2’ is an optionally substituted —(CH) n -C(O) u (NR1) v (SO2) w alkyl group, optionally substituted -(CH2) n -C(O) u (NR1) v (SO2) w NR 1N R 2N , optionally substituted -(CH2) n -C(O) u (NR1) v (SO2)w -aryl group, optionally substituted -(CH) n -C(O) u (NR1) v (SO2) w -heteroaryl group, optionally substituted -(CH) n -C(O) u (NR1) v (SO2) w -heterocycloalkyl group, optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w -alkyl group, optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w NR 1N R 2N , optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w NR1C(O)R 1N , optionally substituted -NR 1 -(CH2)nC(O) u (NR1) v (SO2) w -aryl group, optionally substituted -NR 1 -(CH2) n -aryl-heteroaryl group, optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w -heteroaryl group, optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w -heterocycloalkyl group, optionally substituted -X R2’ -alkyl group, optionally substituted -XR2’ -aryl group, optionally substituted -X R2’ -heteroaryl group, optionally substituted -X R2’ -heterocycloalkyl, R 3’ is an optionally substituted alkyl group, optionally substituted -(CH2) n (O) u (NR1)v(SO2) w -alkyl group, optionally substituted -(CH2) n C(O) u (NR1)v(SO2) w -NR 1N R 2N , optionally substituted -(CH2) n C(O) u (NR1) v (SO2) w -C(O)NR1R2, optionally substituted -(CH2) n C(O) u (NR1) v (SO2) w -aryl group, optionally substituted -(CH) n C(O) u (NR1) v (SO2) w -heteroaryl group, optionally substituted -(CH) n C(O) u (NR1) v (SO2) w -heterocycloaryl group, optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w -alkyl group, optionally substituted -NR 1 -(CH2)nC(O) u (NR1) v (SO2) w -NR 1N R 2N , optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v(SO2) w -NR1C(O)R 1N , optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w -aryl group, optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w -heteroaryl group, optionally substituted -NR 1 -(CH2) n -C(O) u (NR1) v (SO2) w -heterocycloalkyl group, optionally substituted -O-(CH) n -C(O) u (NR1) v (SO2) w -alkyl group, optionally substituted -O-(CH) n -C(O) u (NR1) v (SO2) w -NR 1N R 2N , optionally substituted —O—(CH) n -C(O) u (NR1) v (SO2) w -NR1C(O)R 1N , optionally substituted —O—(CH) n -C(O) u (NR1) v (SO2) w -aryl group, optionally substituted -O-(CH) n -C(O) u (NR1) v (SO2) w -heteroaryl group, optionally substituted -O-(CH) n -C(O) u (NR1) v (SO2) w -heterocycloalkyl group, -(CH2)n -(V) n’ -(CH2) n -(V) n’ -alkyl group, optionally substituted -(CH2) n -(V) n’ -(CH2) n -(V) n’ -aryl group, optionally substituted -(CH) n -(V) n’ -(CH2) n -(V) n’ -heteroaryl group, optionally substituted -(CH) n -(V) n’ -(CH2) n -(V) n’ -heterocycloalkyl group, optionally substituted -(CH) n -N(R 1’ )[C(O)] m’ -(V) n’ -alkyl group, optionally substituted -(CH2) n -N(R 1’ )[C(O)] m’ -(V) n’ -aryl group, optionally substituted -(CH) n -N(R 1’ )[C(O)] m’ -(V) n’ -heteroaryl group, optionally substituted -(CH) n -N(R 1’ )[C(O)] m’ -(V) n’ -heterocycloalkyl group, optionally substituted -X R3’ -alkyl group, optionally substituted -X R3’ -aryl group, optionally substituted -X R3’ -heteroaryl group, optionally substituted -X R3’ -heterocycloalkyl group, R 1N and R 2N are each independently hydrogen, optionally substituted —(CH) n -aryl group, optionally substituted -(CH) n-heteroaryl group, optionally substituted -(CH) n heterocycloalkyl groups, C1-C6 alkyl groups, which C1-C6 alkyl groups are optionally substituted with one or two hydroxy groups or optionally substituted with one, two or three halogens; V is O, S or NR1; R 1 and R 1’ are each independently hydrogen or a C1-C3 alkyl group; X R2’ or X R3’ are each independently optionally substituted —(CH) n -, -(CH2) n -CH(X v )=CH(X v )-(cis or trans), -(CH2) n -C≡CH-, -(CH2CH2O)- or a C3-C6 cycloalkyl group, and v is hydrogen, halogen or an optionally substituted C1-C3 alkyl group; m is independently 0, 1, 2, 3, 4, 5, or 6; m' is independently 1 or 2; n is independently 0, 1, 2, 3, 4, 5, or 6; n' is independently 0 or 1; Each u is independently 0 or 1; v is independently 1 or 2; Each w is independently 0 or 1.

[0337] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E23, E23a, E23b, E23c, E23d or E23e, [ka] Here, in the above E23, E23a, E23b, E23c, E23d and E23e, R 1’ , R 2’ , R 3’ , where X is defined as in E22; R5 and R6 are independently selected from OH, SH, or an optionally substituted alkyl group, or R5 and R6 together with the carbon atom to which they are attached form C=O; R7 is H or an optionally substituted alkyl group; E is a bond, C=O or C=S; G is a bond, an optionally substituted alkyl group, —COOH, or C═J; J is O or N-R8; R8 is H, CN, an optionally substituted alkyl group or an optionally substituted alkoxy group; M is an aryl group, a heteroaryl group, a heterocyclyl group, or [ka] wherein the aryl, heteroaryl, and heterocyclyl groups are optionally substituted; R9, R 10 are independently selected from H, an alkyl group, a cycloalkyl group, a hydroxyalkyl group, a thioalkyl group, a disulfide bond linked to ULM, a heteroaryl group, or a haloalkyl group, and the alkyl group, cycloalkyl group, hydroxyalkyl group, thioalkyl group, a disulfide bond linked to ULM, a heteroaryl group, or a haloalkyl group may be optionally substituted, or R, R 10 together with the carbon atoms to which they are attached form an optionally substituted cycloalkyl group; R 11 is a heterocycloalkyl group, an alkoxy group, a heteroaryl group, an aryl group, or [ka] wherein the heterocycloalkyl group, alkoxy group, heteroaryl group, and aryl group may be optionally substituted; R 12 is H or an optionally substituted alkyl group, R 13 is H, an alkyl group, an alkyl-C=O, a (cycloalkyl)alkyl-C=O, an arylalkyl-C=O, an aryl-C=O, a (heterocycloalkyl)-C=O, an arylalkyl group or an alkoxy-C=O, wherein said alkyl group, alkyl-C=O, a (cycloalkyl)alkyl-C=O, an arylalkyl-C=O, an aryl-C=O, a (heterocycloalkyl)-C=O, an arylalkyl group or an alkoxy-C=O may be optionally substituted; R 14 is H, a haloalkyl group, a cycloalkyl group, an alkyl group, or a heterocycloalkyl group, which cycloalkyl group, alkyl group, or heterocycloalkyl group may be optionally substituted; R 15 is H, a heteroaryl group, a haloalkyl group, an aryl group, an alkoxy group, or a heterocycloalkyl group, which heteroaryl group, haloalkyl group, aryl group, alkoxy group, or heterocycloalkyl group may be optionally substituted; R 16 is a halogen, an alkyl group, a haloalkyl group, CN, or a haloalkoxy group, wherein the alkyl group, haloalkyl group, or haloalkoxy group may be optionally substituted; R 17 is H, halogen, a cycloalkyl group, an alkyl group, an alkenyl group, or a haloalkyl group, wherein the cycloalkyl group, the alkyl group, or the alkenyl group may be optionally substituted; R 23 is H or OH, R 25 is H or a substituted alkyl group, or two R 25 forms a ═O or substituted cycloalkyl group, Z1, Z2, Z3 and Z4 are each independently selected from C or N; X is O or S; Y is H, a methyl group, or an ethyl group; o is 0, 1, 2, 3 or 4.

[0338] In some embodiments, in E23, E23a, E23b, E23c, E23d, and E23e, R 1’ , R 2’ , R 3’ , R5, R6, R7, R9, R 10 , R 11 , R 14 , R 15 , R 16 , R 17 , R 23 , R 25 , E, M, o, X, Y, Z1, Z2, Z3 and Z4 are as defined and explained in US 2016 / 0272639, the entire contents of which are incorporated herein by reference.

[0339] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E23a, [ka] Here, in E23a above, R 1’ is a hydroxy group, R 2’ is -NH-CH-aryl-HET, R 3’ is an optionally substituted alkyl group, —(CH)R CR3’ -NH-C(O)-R 3p1 or -(CH)R CR3’ -R 3p2 Selected from R CR3’ is an optionally substituted C1-C4 alkyl group, R 3p1 is an optionally substituted C1-C6 alkyl group, an optionally substituted oxetane group, -(CH2) nOCH3, a phenyl group optionally substituted with -O(CH2CH3), or a morpholinyl group linked to a carbonyl group at the 2- or 3-position, wherein n is 1 or 2; R 3p2 teeth, [ka] or an optionally substituted phenyl group; HET is selected from optionally substituted thiazole, oxazole, isoxazole, or isothiazole; R HET is selected from hydrogen, halogen, cyano, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, and optionally substituted aryl.

[0340] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E23c, [ka] or a pharmaceutically acceptable salt thereof, wherein in the above E23c: each R5 and R6 is independently -OH, -SH, or an optionally substituted alkyl group, or R5, R6 together with the carbon atom to which they are attached form a carbonyl group; R7 is H or an optionally substituted alkyl group; E is a bond, C=O or C=S; G is a bond, an optionally substituted alkyl group, —COOH, or C═J; J is O or N-R8; R8 is H, CN, an optionally substituted alkyl group or an optionally substituted alkoxy group; M is an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted heterocycloalkyl group, or [ka] and Each R9 and R 10 are independently H, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted hydroxyalkyl group, an optionally substituted thioalkyl group, a ULM linked by a disulfide bond, an optionally substituted heteroaryl group or a haloalkyl group, or R, R 10 form an optionally substituted cycloalkyl group together with the carbon atom to which they are attached; R 11 is an optionally substituted heterocycloalkyl group, an optionally substituted alkoxy group, an optionally substituted heteroaryl group, an optionally substituted aryl group, or [ka] and R 12 is H or an optionally substituted alkyl group, R 13 is H, an optionally substituted alkyl group, an optionally substituted alkylcarbonyl group, an optionally substituted (cycloalkyl)alkylcarbonyl group, an optionally substituted arylalkylcarbonyl group, an optionally substituted arylcarbonyl group, an optionally substituted (heterocycloalkyl)carbonyl group or an optionally substituted arylalkyl group, an optionally substituted (oxoalkyl)carbamate; Each R 14 are independently H, a haloalkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkyl group, or an optionally substituted heterocycloalkyl group; Each R 15 H, an optionally substituted heteroaryl group, a haloalkyl group, an optionally substituted aryl group, an optionally substituted alkoxy group, or an optionally substituted heterocycloalkyl group; Each R16 are independently halogen, an optionally substituted alkyl group, an optionally substituted haloalkyl group, CN, or an optionally substituted haloalkoxy group; Each R 25 are independently H or an optionally substituted alkyl group, or two R 25 the groups can together form an oxo or an optionally substituted cycloalkyl group, R 23 is H or OH, Z1, Z2, Z3 and Z4 are independently C or N, and o is 0, 1, 2, 3 or 4.

[0341] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E23d, [ka] Here, in the above E23d, X is O or S; Y is H, a methyl group, or an ethyl group; R 17 is H, a methyl group, an ethyl group, a hydroxymethyl group, or a cyclopropyl group, M is an optionally substituted heteroaryl group, an optionally substituted aryl group.

[0342] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E23d-1, [ka] Here, in the above E23d-1, Y is H, a methyl group, or an ethyl group; R9 is H, R 10 is an isopropyl group, a tert-butyl group, a sec-butyl group, a cyclopentyl group, or a cyclohexyl group, R 11 is an optionally substituted amide, an optionally substituted isodihydroindolinone, an optionally substituted isoxazole, an optionally substituted heterocycle; R 17 is H, a methyl group, an ethyl group, a hydroxymethyl group, or a cyclopropyl group.

[0343] In a preferred embodiment of the compound of Formula I of the present invention, and / or its stereoisomer, enantiomer, diastereomer, deuterated form, hydrate, solvate, prodrug and / or pharmaceutically acceptable salt thereof, E is a specific compound of Examples 1 to 208 in CN108601764 (the entire text of which is incorporated herein by reference).

[0344] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E24, [ka] or a pharmaceutically acceptable salt thereof, wherein in E24 above, X 1 , X 2 are each independently a bond, O, or NR Y3 , C.R. Y3 R Y4 , C=O, C=S, SO or SO2; R Y3 , R Y4 are each independently hydrogen, a C1-C6 alkyl group optionally substituted with one or more halogens, and optionally 0 to 3 R p is a C1-C6 alkoxy group substituted with R pis 0, 1, 2 or 3 groups selected from hydrogen, halogen, hydroxyl group, C1-C3 alkyl group or C(=O), W 3 is an optionally substituted T, an optionally substituted -TN(R 1a R 1b )X 3 , optionally substituted -TN(R 1a R 1b ), an optionally substituted -T-aryl group, an optionally substituted -T-heteroaryl group, an optionally substituted -T-bicyclic heteroaryl group, an optionally substituted -T-heterocycloalkyl group, an optionally substituted -T-bicyclic heterocycloalkyl group, an optionally substituted -NR 1 -T-aryl group, optionally substituted -NR 1 -T-heteroaryl group or optionally substituted -NR 1 -T-heterocycloalkyl groups, X 3 is C(O), R 1 , R 1a or R 1b and Each R 1 , R 1a or R 1b are each independently hydrogen, a C1-C6 alkyl group optionally substituted with one or more halogen or hydroxy groups, R Y3 C(O), R Y3 C(S), R Y3 S(O), R Y3 S(O)2, N(R Y3 R Y4) C(O), N(R Y3 R Y4) C(S), N(R Y3 R Y4) S(O) or N(R Y3 R Y4) Selected from S(O)2, T is an optionally substituted alkyl group, -(CH2) n-, wherein each methylene group is optionally selected from a halogen, a hydroxy group, an optionally substituted amino acid side chain, a methyl group, an optionally substituted alkoxy group, a C1-C6 alkyl group optionally substituted with one or more halogens, -C(O)NR 1 R 1a or NR 1 R 1a is substituted with a substituent selected from Or R 1 and R 1a can optionally form an optionally substituted heterocycloalkyl group, n is 0, 1, 2, 3, 4, 5, or 6; W 4 teeth, [ka] and R 14a and R 14b are each independently hydrogen, a haloalkyl group, or an optionally substituted alkyl group; W 5 is an optionally substituted phenyl group or an optionally substituted heteroaryl group; R 15 is an optionally substituted hydrogen, cyano group, halogen, hydroxy group, nitro group, NR 14a R 14b , OR 14a ,CONR 14a R 14b , N.R. 14a CONR 14b、 SO2NR 14a R 14b , N.R. 14a SO2R 14b , optionally substituted alkyl groups, optionally substituted haloalkyl groups, optionally substituted haloalkoxy groups, optionally substituted aryl groups, optionally substituted heteroaryl groups, optionally substituted cycloalkyl groups, and optionally substituted heterocycloalkyl groups.

[0345] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E25 or E25a, [ka] Here, in the above E25 and E25a, The above W 3 is an optionally substituted aryl group, an optionally substituted heteroaryl group, or [ka] and R9 and R 10 are each independently hydrogen, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted hydroxyalkyl group, an optionally substituted heteroaryl group, a haloalkyl group, or R and R 10 together with the carbon atoms to which they are attached form an optionally substituted cycloalkyl group; R 11 is an optionally substituted heterocycloalkyl group, an optionally substituted alkoxy group, an optionally substituted heteroaryl group, an optionally substituted aryl group, [ka] Selected from R 12 are each independently hydrogen or an optionally substituted alkyl group; R 13 are each independently hydrogen, an optionally substituted alkyl group, an optionally substituted alkylcarbonyl group, an optionally substituted (cycloalkyl)alkylcarbonyl group, an optionally substituted arylalkylcarbonyl group, an optionally substituted arylcarbonyl group, an optionally substituted (heterocycloalkyl)carbonyl group, or an optionally substituted arylalkyl group; R 14a , R 14b are each independently hydrogen, a haloalkyl group, or an optionally substituted alkyl group; W 5 is selected from an optionally substituted phenyl group or an optionally substituted 5- to 10-membered heteroaryl group; R 15 is an optionally substituted hydrogen, cyano group, halogen, hydroxy group, nitro group, NR 14a R 14b , OR 14a ,CONR 14a R 14b , N.R. 14a CONR 14b , SO2NR 14a R 14b , N.R. 14a SO2R 14b , an optionally substituted alkyl group, an optionally substituted haloalkyl group, an optionally substituted haloalkoxy group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted cycloalkyl group, an optionally substituted heterocycloalkyl group; Each R 16 are each independently a halogen, a cyano group, an optionally substituted alkyl group, an optionally substituted alkoxy group, a hydroxy group, or an optionally substituted haloalkyl group; o is 0, 1, 2, 3 or 4; R 18 are each independently selected from a halogen, an optionally substituted alkoxy group, a cyano group, an optionally substituted alkyl group, a haloalkyl group, and a haloalkoxy group; p is 0, 1, 2, 3 or 4.

[0346] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E26, E26a or E26b, [ka] or a pharmaceutically acceptable salt thereof, wherein in E26, E26a and E26b above: R1 is hydrogen, methyl, ethyl, isopropyl, tert-butyl, sec-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, optionally substituted alkyl, optionally substituted hydroxyalkyl, optionally substituted heteroaryl or haloalkyl; R 14a is hydrogen, a haloalkyl group, an optionally substituted alkyl group, a methyl group, a fluoromethyl group, a hydroxymethyl group, an ethyl group, an isopropyl group, or a cyclopropyl group; X is CH2 or C(O), R 15 is selected from hydrogen, halogen, CN, a hydroxy group, a nitro group, an optionally substituted heteroaryl group, an optionally substituted aryl group, an optionally substituted alkyl group, an optionally substituted haloalkyl group, an optionally substituted haloalkoxy group, an optionally substituted cycloalkyl group, or an optionally substituted heterocycloalkyl group; R3 is absent or an optionally substituted 5-6 membered heteroaryl group.

[0347] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E27, E27a, E27b, E27c, E27d, E27e, E27f and E27g, [ka] In the above E27, E27a, E27b, E27c, E27d, E27e, E27f and E27g, X is carbon, oxygen, sulfur, sulfoxide, sulfone and NR a Selected from R aare independently H or an alkyl group having 1 to 6 carbon atoms, Y and Z are independently carbon or nitrogen; A, A' and A'' are independently selected from C, N, O or S and may be one or two atoms forming a fused bicyclic ring, or a 6,5 ​​and 5,5-fused aromatic bicyclic group; R1 and R2 are independently selected from an aryl group or a heteroaryl group, and a heteroaryl group having 1 or 2 heteroatoms independently selected from sulfur or nitrogen, wherein the aryl group or heteroaryl group may be monocyclic or bicyclic, or unsubstituted or substituted with 1 to 3 substituents, and the substituents are independently selected from halogen, -CN, a C1-C6 alkyl group, a C3-C6 cycloalkyl group, -OH, an alkoxy group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms substituted with fluorine, a sulfoxide having 1 to 6 carbon atoms, a sulfone having 1 to 6 carbon atoms, a ketone having 2 to 6 carbon atoms, an amide having 2 to 6 carbon atoms, and a dialkylamine having 2 to 6 carbon atoms; R3 and R4 are independently selected from H, a methyl group, and a C1-C6 alkyl group; R5 is selected from an aryl group or a heteroaryl group, or a heteroaryl group having 1 or 2 heteroatoms independently selected from sulfur or nitrogen, wherein the aryl group or heteroaryl group may be monocyclic or bicyclic, or unsubstituted or substituted with 1 to 3 substituents, and the substituents are independently selected from halogen, -CN, a C1-C6 alkyl group, a C3-C6 cycloalkyl group, -OH, an alkoxy group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms substituted with fluorine, a sulfoxide having 1 to 6 carbon atoms, a sulfone having 1 to 6 carbon atoms, a ketone having 2 to 6 carbon atoms, an amide having 2 to 6 carbon atoms, a dialkylamine having 2 to 6 carbon atoms, an alkyl ether (C2-C6), an alkyl ketone (C3-C6), a morpholinyl group, an alkyl ester (C3-C6), and an alkylcyano (C3-C6); R6 is H or -C(=O)R b where R bis an alkyl group, a cycloalkyl group, a mono-, di- or tri-substituted aryl or heteroaryl group, a 4-morpholinyl group, a 1-(3-oxopiperazinyl), a 1-piperidinyl group, a 4-NR c -morpholinyl, 4-R c -1-piperidinyl and 3-R c -1-piperidinyl, wherein R c is an alkyl group, an alkyl group substituted with fluorine, a cyanoalkyl group, an alkyl group substituted with a hydroxy group, a cycloalkyl group, an alkoxyalkyl group, an amidoalkyl group, an alkylsulfone, an alkylsulfoxide, an alkylamide, an aryl group, a heteroaryl group, a mono-, di- or tri-substituted aryl or heteroaryl group, CH2CH2R d and CH2CH2CH2R d Selected from, here R d is selected from an alkoxy group, an alkyl sulfone, an alkyl sulfoxide, an N-substituted formamide, an -NHC(O)-alkyl group, an -NH-SO2-alkyl group, an aryl group, a substituted aryl group, a heteroaryl group, and a substituted heteroaryl group; R7 is selected from H, a C1-C6 alkyl group, a cycloalkyl group, an alkyl group substituted with a fluorine group, an alkyl group substituted with a cyano group, a 5- or 6-membered heteroaryl group or aryl group, and a substituted 5- or 6-membered heteroaryl group or aryl group; R8 is -R e -C(O)-R f , -R e -alkoxy, -R e -aryl group, -R e -heteroaryl and -R e -C(O)-R f -C(O)-R g where: R e is an alkylene group having 1 to 6 carbons or a bond; R f is a substituted 4- to 7-membered heterocycle, R gis selected from an aryl group, a heteroaryl group, a substituted aryl group or heteroaryl group, and a 4- to 7-membered heterocycle; R9 is selected from mono-, di-, or tri-substituted groups on a fused bicyclic aromatic ring, wherein said substituents are independently selected from halogen, alkene, alkyne, alkyl group, unsubstituted or substituted with Cl or F; R 10 is selected from an aryl group or a heteroaryl group, wherein the heteroaryl group may contain one or two heteroatoms such as sulfur or nitrogen, the aryl group or the heteroaryl group may be monocyclic or bicyclic, and the aryl group or the heteroaryl group may be unsubstituted or substituted with 1 to 3 substituents including halogen, F, Cl, -CN, alkene, alkyne, C1-C6 alkyl group, C1-C6 cycloalkyl group, -OH, an alkoxy group having 1 to 6 carbons, an alkoxy group having 1 to 6 carbons substituted with fluorine, a sulfoxide having 1 to 6 carbons, a sulfone having 1 to 6 carbons, or a ketone having 2 to 6 carbons; R 11 is -C(O)-N(R h )(R i ), where R h and R i is selected from H, C1-C6 alkyl groups, alkoxy-substituted alkyl groups, sulfone-substituted alkyl groups, aryl groups, heteroaryl groups, mono-, di-, or tri-substituted aryl or heteroaryl groups, alkylcarboxylic acids, heteroarylcarboxylic acids, fluorine-substituted alkylcarboxylic acids, aryl-substituted cycloalkyl groups, and heteroaryl-substituted cycloalkyl groups, wherein R h and R i are independently selected from H, a ring formed by linking, 4-hydroxycyclohexane, alkyl groups (C3-C6) substituted with monohydroxy and dihydroxy groups, 3-hydroxycyclobutane, phenyl-4-carboxylic acid, and substituted phenyl-4-carboxylic acids; R 12 and R 13are independently selected from H, lower alkyl (C1-C6), lower alkenyl (C2-C6), lower alkynyl (C2-C6), cycloalkyl (4-, 5-, and 6-membered), substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, 5- and 6-membered aryl, and heteroaryl; R 12 and R 13 can be linked to form 5- and 6-membered rings with or without ring substitution; R 14 is selected from alkyl groups, substituted alkyl groups, alkenyl groups, substituted alkenyl groups, aryl groups, substituted aryl groups, heteroaryl groups, substituted heteroaryl groups, heterocycles, substituted heterocycles, cycloalkyl groups, substituted cycloalkyl groups, cycloalkenyl groups and substituted cycloalkenyl groups; R 15 is CN, R 16means a C1-C6 alkyl group, a C1-C6 cycloalkyl group, a C2-C6 alkenyl group, a C1-C6 alkyl group or a C3-C6 cycloalkyl group in which one or more hydrogen atoms are substituted with fluorine; an alkyl group or cycloalkyl group in which one CH2 is substituted with S(=O), -S or -S(=O)2; an alkyl group or cycloalkyl group in which the terminal CH3 is substituted with S(=O)2N(alkyl)(alkyl), -C(=O)N(alkyl)(alkyl), -N(alkyl)S(=O)2(alkyl), -C(=O)2(alkyl), -O(alkyl); a C1-C6 alkyl group or alkyl-cycloalkyl group in which a hydrogen atom is substituted with a hydroxy group. an alkyl group, a 3- to 7-membered cycloalkyl or heterocycloalkyl group, a group optionally containing -(C=O)-, or a 5- or 6-membered aryl or heteroaryl group, wherein the heterocycloalkyl or heteroaryl group may contain 1 to 3 heteroatoms independently selected from O, N or S, and the cycloalkyl, heterocycloalkyl, aryl or heteroaryl group may be unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, C1-C6 alkyl group, hydroxylated C1-C6 alkyl group, C1-C6 alkyl group including thioether, ether, sulfone, sulfoxide, fluorine-substituted ether or cyano group; R 17 is (CH2) n C(O)NR k R l where R k and R lare independently selected from H, a C1-C6 alkyl group, a hydroxylated C1-C6 alkyl group, a C1-C6 alkoxyalkyl group, a C1-C6 alkyl group in which one or more hydrogens are substituted with fluorine, a C1-C6 alkyl group in which one carbon is substituted with S(O) or S(O)(O), a C1-C6 alkoxyalkyl group in which one or more hydrogens are substituted with fluorine, a C1-C6 alkyl group in which one or more hydrogens are substituted with a cyano group, a 5- and 6-membered aryl or heteroaryl group, an alkylaryl group in which the alkyl group contains 1 to 6 carbons, and an alkylheteroaryl group in which the alkyl group contains 1 to 6 carbons, wherein the aryl or heteroaryl group may be further substituted, and n is an integer of 0 to 6, R 18 is selected from substituted aryl, heteroaryl, alkyl, and cycloalkyl groups, and the substitution is preferably -N(C1-C4 alkyl)(cycloalkyl), -N(C1-C4 alkyl)alkyl-cycloalkyl, and -N(C1-C4 alkyl)[(alkyl)-(heterocyclic substituted)-cycloalkyl; R 19 is selected from an aryl group, a heteroaryl group, and a bicyclic heteroaryl group, and these aryl groups or heteroaryl groups may be substituted with halogen, a C1-C6 alkyl group, a C1-C6 cycloalkyl group, CF3, F, CN, an alkyne, or an alkylsulfone, and the halogen substitution may be mono- or tri-substituted; R 20 and R 21 are independently selected from a C1-C6 alkyl group, a C1-C6 cycloalkyl group, a C1-C6 alkoxy group, a hydroxylated C1-C6 alkoxy group, and a fluorine-substituted C1-C6 alkoxy group, wherein R 20 and R 21 may be linked to form a 5-, 6-, or 7-membered ring or heterocycle, which may be further substituted; R 22is selected from H, a C1-C6 alkyl group, a C1-C6 cycloalkyl group, a carboxylic acid, a carboxylate, an amide, a reverse amide, a sulfonamide, a reverse sulfonamide, an N-acylurea, and a nitrogen-containing 5-membered heterocycle, and the 5-membered heterocycle may be further substituted with a C1-C6 alkyl group, an alkoxy group, an alkyl group substituted with fluorine, CN, or an alkylsulfone; R 23 is selected from an aryl group, a heteroaryl group, an -O-aryl group, an -O-heteroaryl group, an -O-alkyl group, an -O-alkyl-cycloalkyl group, an -NH-alkyl group, an -NH-alkyl-cycloalkyl group, an -N(H)-aryl group, an -N(H)-heteroaryl group, an -N(alkyl)-aryl group, and an -N(alkyl)-heteroaryl group, wherein the aryl group or the heteroaryl group is optionally substituted with a halogen, a C1-C6 alkyl group, a hydroxylated C1-C6 alkyl group, a cycloalkyl group, a C1-C6 alkyl group substituted with fluorine, CN, an alkoxy group, an alkylsulfone, an amide, and a sulfonamide; R 24 is selected from -CH2-(C1-C6 alkyl), -CH2-cycloalkyl, -CH2-aryl, and CH2-heteroaryl, wherein the alkyl, cycloalkyl, aryl, and heteroaryl groups are optionally substituted with halogen, alkoxy, hydroxylated alkyl, cyano-substituted alkyl, cycloalkyl, and substituted cycloalkyl groups; R 25 is selected from a C1-C6 alkyl group, a C1-C6 alkyl-cycloalkyl group, an alkyl group substituted with an alkoxy group, a hydroxylated alkyl group, an aryl group, a heteroaryl group, a substituted aryl or heteroaryl group, a 5-, 6- and 7-membered nitrogen-containing saturated heterocycle, a 5,6-fused and a 6,6-fused nitrogen-containing saturated heterocycle, and these saturated heterocycles may be substituted with a C1-C6 alkyl group, a C1-C6 alkyl group substituted with a fluorine group, an alkoxy group, an aryl group and a heteroaryl group; R 26is selected from a C1-C6 alkyl group and a C3-C6 cycloalkyl group, wherein the alkyl group or cycloalkyl group may be substituted with -OH, an alkoxy group, a fluorine-substituted alkoxy group, a fluorine-substituted alkyl group, -NH2, an -NH-alkyl group, an NH-C(O)alkyl group, an -NH-S(O)2-alkyl group and an -S(O)2-alkyl group; R 27 is selected from an aryl group, a heteroaryl group, and a bicyclic heteroaryl group, wherein the aryl group or heteroaryl group is optionally substituted with a C1-C6 alkyl group, an alkoxy group, NH2, an NH-alkyl group, a halogen, or -CN, and the substitutions may be independently mono-, di-, or tri-substituted; R 28 is selected from aryl groups, 5- and 6-membered heteroaryl groups, bicyclic heteroaryl groups, cycloalkyl groups, saturated heterocycles such as piperidine, piperidone, tetrahydropyran, N-acyl-piperidine, etc., wherein the cycloalkyl groups, saturated heterocycles, aryl groups, or heteroaryl groups may be further substituted with alkyl groups which may be mono-, di-, or tri-substituted with substituents including -OH, alkoxy groups, halogen, -CN, alkylsulfone, and fluorine; and R 1” is selected from an alkyl group, an alkyl group substituted with an aryl group, an alkyl group substituted with an alkoxy group, a cycloalkyl group, a cycloalkyl group substituted with an aryl group, and a cycloalkyl group substituted with an alkoxy group.

[0348] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E28, E28a, E28b, E28c, E28d, E28e, E28f, E28g, E28h or E28i (MDM2), [ka] [ka] Here, in the above E28, E28a, E28b, E28c, E28d, E28e, E28f, E28g, E28h and E28i, R 1’ and R 2’ are each independently F, Cl, Br, I, an ethynyl group, a cyano group, a nitro group, or CF3; R 3’ is selected from -OCH3, -OCH2CH3, -OCH2CH2F, -OCH2CH2OCH3 or -OCH(CH3)2, R 4’ is selected from hydrogen, halogen, methyl, -CF3, -OCH3, -C(CH3)3, -CH(CH3)2, -cyclopropyl, cyano, -C(CH3)2OH, -C(CH3)2OCH2CH3, -C(CH3)2OCH2OH, -C(CH3)2CH2OCH2CH3, -C(CH3)2CH2OCH2CH2OH, -C(CH3)2CN, -C(CH3)2C(O)CH3, -C(CH3)2C(O)NHCH3, -C(CH3)2C(O)N(CH3)2, -SCH3, -SCH2CH3, -S(O)2CH3, -S(O)2CH2CH3, -NHC(CH3)3, -NC(CH3)2, pyrrolidinyl or morpholinyl; R 5’ is selected from halogen, a cyclopropyl group, —S(O)2CH3, —S(O)2CH2CH3, a pyrrolidinyl group, —NH2, —N(CH3)2 or —NHC(CH3)3, R 6’ is hydrogen, [ka] where R 6’ In the formula, the x is a connection point connecting to L, or R 4’ may be linked to L, R 7’ is one or more halogens, R 8’is one or more selected from hydrogen, F, Cl, Br, I, cyano group, nitro group, ethynyl group, cyclopropyl group, methyl group, ethyl group, isopropyl group, vinyl group, methoxy group, ethoxy group, isopropoxy group, hydroxy group, other C1-C6 alkyl group, other C1-C6 alkenyl group, and other C1-C6 alkynyl group; R 9’ is an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted cycloalkyl group; Z is hydrogen, —OCH3, —OCH2CH3 or halogen; R 10’ and R 11’ are each independently hydrogen, (CH2) n -R', (CH2) n -NR'R'', (CH2) n -NR'C(O)R'', (CH2) n -NR'S(O)2R'', (CH2) n -C(O)OH, (CH2) n -C(O)OR', (CH2) n -C(O)NR'R'', (CH2) n -OR', (CH2) n -SR', (CH2) n -SOR', (CH2) n -CH(OH)-R', (CH2) n -C(O)R', (CH2) n -S(O)R', (CH) n -S(O)NR'R'', (CH2) n -S(O)NR'R'', (CHCHO) m -(CH2) n -R', (CH2CH2O) m -(CH2) n -OH, (CH2CH2O) m -(CH2) n -OR', (CH2CH2O) m -(CH2) n-NR’R’’、(CH2CH2O) m -(CH2) n -NR’C(O)R’’、(CH2CH2O) m -(CH2) n -S(O)2NR’R’’、(CH2CH2O) m -(CH2) n -C(O)OH、(CH2CH2O) m -(CH2) n -C(O)OR’、(CH2CH2O) m -(CH2) n -C(O)NR’R’’、(CH2CH2O) m -(CH2) n -S(O)OR’、(CH2CH2O) m -(CH2) n -C(O)R’、(CH2CH2O) m -(CH2) n -S(O)NR’R’’、(CH2CH2O) m -(CH2) n -S(O)2NR’R’’、-(CH2) p -(CH2CH2O) m -(CH2) n R’、-(CH2) p -(CH2CH2O) m -(CH2) n -OH、-(CH2) p -(CH2CH2O) m -(CH2) n -OR’、-(CH2) p -(CH2CH2O) m -(CH2) n -NR’R’’、-(CH2) p -(CH2CH2O) m -(CH2) n -NR’C(O)R’’、-(CH2) p -(CH2CH2O) m -(CH2) n -NR’S(O)2R’’、-(CH2) p -(CH2CH2O) m -(CH2) n -C(O)OH、-(CH2) p -(CH2CH2O) m -(CH2)n -C(O)OR', -(CH2) p -(CH2CH2O) m -(CH2) n -C(O)NR'R'', -(CH2) p -(CH2CH2O) m -(CH2) n -S(O)R', -(CH) p -(CH2CH2O) m -(CH2) n -C(O)R', -(CH2) p -(CH2CH2O) m -(CH2) n -S(O)NR'R'', -(CH2) p -(CH2CH2O) m -(CH2) n -S(O)2NR'R'', aryl-(CH2) n -C(O)OH or heteroaryl-alkyl-C(O)-alkyl-NR'R'' wherein the alkyl group is optionally substituted with OR', or R 10’ and R 11’ are each independently heteroaryl-(CH2) n -heterocycloalkyl, wherein the heterocycloalkyl group is optionally substituted with alkyl, hydroxy, C(O)OR', or C(O)R', wherein R' and R'' are each independently hydrogen, halogen, hydroxy, NH, NH(alkyl), NH(alkyl) 1-2 , oxo, carboxy, cycloalkyl or heteroaryl; m, n, and p are each independently 0, 1, 2, 3, 4, 5, or 6; R 12’ are each independently an -O-alkyl group, an -O-alkyl-alkoxy group, a -C(O)-alkyl group, a -C(OH)-alkyl-alkoxy group, a -C(O)-NH-alkyl group, a -C(O)-N-(alkyl) 1-2 , -S(O)-alkyl group, S(O)2-alkyl group, -C(O)-cycloamine, -O-aryl-alkyl group, -O-aryl-alkoxy; R 1’’is selected from hydrogen, an alkyl group optionally substituted with an aryl group or an alkoxy group, and a cycloalkyl group optionally substituted with an aryl group or an alkoxy group.

[0349] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E29, [ka] R1 is independently H, a C1-C4-alkyl group, a C1-C4-alkenyl group, a C1-C4-alkynyl group or a C3-C 10 -cycloalkyl groups, which may be unsubstituted or substituted, R2 is independently H, a C1-C4-alkyl group, a C1-C4-alkenyl group, a C1-C4-alkynyl group or a C3-C 10 -cycloalkyl groups, which may be unsubstituted or substituted, R3 is independently selected from H, -CF3, -C2H5, C1-C4-alkyl groups, C1-C4-alkenyl groups, C1-C4-alkynyl groups, -CH2-Z, or optionally R2 and R3 together form a heterocycle; each Z is independently selected from H, —OH, F, Cl, —CH, —CF, —CHCl, —CHF, or —CHOH; R4 is independently C1-C 16 Straight or branched chain alkyl groups, C1-C 16 -Alkenyl group, C1-C 16 -Alkynyl group, C3-C 10 -cycloalkyl group, -(CH2) 0-6 -Z1, -(CH2) 0-6 -aryl groups and -(CH2) 0-6 -het, wherein the alkyl, cycloalkyl and phenyl groups are unsubstituted or substituted; R5 is independently H, C 1-10 -Alkyl group, aryl group, phenyl group, C 3-7 -cycloalkyl group, -(CH2)1-6 -C 3-7 -cycloalkyl group, -C 1-10 -Alkyl-aryl group, -(CH2) 0-6 -C 3-7 -Cycloalkyl-(CH2) 0-6 -phenyl group, -(CH2) 0-4 -CH[(CH2) 1-4 -phenyl]2, indanyl group, -C(O)-C 1-10 -Alkyl group, -C(O)-(CH2) 1-6 -C 3-7 -cycloalkyl group, -C(O)-(CH2) 0-6 -phenyl group, -(CH2) 0-6 -C(O)-phenyl group, -(CH2) 0-6 -het, -C(O)-(CH2) 1-6 -het, or R5 is selected from the residue of an amino acid, wherein the alkyl, cycloalkyl, phenyl and aryl group substituents are unsubstituted or substituted; Z1 independently represents -N(R 10 )-C(O)-C 1-10 -alkyl group, -N(R 10 )-C(O)-(CH2) 0-6 -C 3-7 -cycloalkyl group, -N(R 10 )-C(O)-(CH2) 0-6 -phenyl group, -N(R 10 )-C(O)(CH2) 1-6 -het, -C(O)-N(R 11 )(R 12 ), -C(O)-OC 1-10 -Alkyl group, -C(O)-O-(CH2) 1-6 -C 3-7 -cycloalkyl group, -C(O)-O-(CH2) 0-6 -phenyl group, -C(O)-O-(CH2) 1-6 -het, -OC(O)-C 1-10 -Alkyl group, -OC(O)-(CH2) 1-6 -C 3-7 -cycloalkyl group, -OC(O)-(CH2) 0-6 -phenyl group, -OC(O)-(CH2) 1-6-het, wherein the alkyl, cycloalkyl and phenyl groups are unsubstituted or substituted; het is independently selected from a 5- to 7-membered heterocycle or an 8- to 12-membered fused ring system containing 1 to 4 heteroatoms selected from N, O, and S, including at least one 5- to 7-membered heterocycle containing 1, 2, or 3 heteroatoms selected from N, O, and S, said heterocycle or fused ring system being unsubstituted or substituted at carbon or nitrogen atoms; R 10 is selected from H, —CH3, —CF3, —CH2OH or —CH2Cl, R 11 and R 12 are independently H, C 1-4 -Alkyl group, C 3-7 -cycloalkyl group, -(CH2) 1-6 -C 3-7 -cycloalkyl group, (CH2) 0-6 -phenyl groups, wherein the alkyl, cycloalkyl and phenyl groups are unsubstituted or substituted, or R 11 and R 12 forms het with nitrogen, and U is independently: [ka] where: each n is independently selected from 0 to 5; X is selected from —CH and N; R a and R b are independently an O, S or N atom or C 0-8 -alkyl groups, wherein one or more carbon atoms in the alkyl group chain are optionally replaced with a heteroatom selected from O, S or N, and wherein each alkyl group is independently unsubstituted or substituted; R d is Re-Q-(R f ) p (R g ) q and Ar1-D-Ar2, R cis selected from H, or any R c and R d together form a cycloalkyl group or het, where R c and R d forms a cycloalkyl group or het, R5 is linked to the ring formed at the C or N atom, p and q are independently selected from 0 or 1; R e is C 1-8 - selected from alkyl groups and alkylene groups, and each R e is unsubstituted or substituted, Q is selected from N, O, S, S(O) and S(O)2; Ar1 and Ar2 are independently selected from substituted or unsubstituted aryl groups and het; R f and R g are independently H, -C 1-10 -Alkyl group, C 1-10 -Alkylaryl groups, -OH, -OC 1-10 -Alkyl group, -(CH2) 0-6 -C 3-7 -cycloalkyl group, -O-(CH2) 0-6 -aryl group, phenyl group, aryl group, phenyl-phenyl group, -(CH2) 1-6 -het, -O-(CH2) 1-6 -het, -OR 13 , -C(0)-R 13 , -C(O)-N(R 13 )(R 14 ), -N(R 13 )(R 14 ), -SR 13 , -S(O)-R 13 , -S(O)2-R 13 , -S(O)2-NR 13 R 14 , -NR 13 -S(O)2-R 14 , -SC t-10 -Alkyl group, aryl-C 1-4 -Alkyl or het-C 1-4-alkyl, where the alkyl, cycloalkyl, het and aryl groups are unsubstituted or substituted; -SO2-C 1-2 -Alkyl group, -SO2-C 1-2 -Alkylphenyl group, -OC 1-4 - an alkyl group or any R g and R f together form a ring selected from het or an aryl group, D is -CO-, -C(O)-C 1-7 -Alkylene or arylene, -CF2-, -O-, -S(O) r , 1,3-dioxacyclopentane or C 1-7 -alkyl-OH, where r is 0 to 2, and the alkyl group, alkylene group or arylene group is unsubstituted or substituted with one or more halogens, OH, -OC 1-6 -Alkyl group, -SC 1-6 -alkyl group or -CF3, or each D is independently N(R h ) are selected from R h is H, unsubstituted or substituted C 1-7 -alkyl group, aryl group, unsubstituted or substituted -O-(C 1-7 -cycloalkyl), -C(O)-C 1-10 -Alkyl group, -C(O)-C 0-10 -Alkyl-aryl group, -COC 1-10 -Alkyl group, -COC 0-10 -Alkyl-aryl group, -SO2-C 1-10 -Alkyl or -SO2-(C 0-10 -alkylaryl), R6, R7, R8 and R9 are independently H, -C 1-10 -alkyl group, -C 1-10 -alkoxy group, aryl-C 1-10 -aryl groups, -OH, -OC 1-10 -Alkyl group, -(CH2) 0-6 -C 3-7 -cycloalkyl group, -O-(CH2) 0-6 -aryl group, phenyl group, -(CH2) 1-6 -het, -O-(CH2)1-6 -het, -OR 13 , -C(O)-R 13 , -C(O)-N(R 13 )(R 14 ), -N(R 13 )(R 14 ), -SR 13 , -S(O)-R 13 , -S(O)2-R 13 , -S(O)2-NR 13 R 14 or -NR 13 -S(O)2-R 14 wherein each of the alkyl, cycloalkyl and aryl groups is unsubstituted or substituted, and any of R, R, R and R optionally together form a ring system; R 13 and R 14 are independently H, C 1-10 -Alkyl group, -(CH2) 0-6 -C 3-7 -cycloalkyl group, -(CH2) 0-6 -(CH) 0-1 -(aryl) 1-2 , -C(O)-C 1-10 -Alkyl group, -C(O)-(CH2) 1-6 -C 3-7 -cycloalkyl group, -C(O)-O-(CH2) 0-6 -aryl group, -C(O)-(CH2) 0-6 -O-fluorenyl group, -C(O)-NH-(CH2) 0-6 -aryl group, -C(O)-(CH2) 0-6 -aryl group, -C(O)-(CH2) 0-6 -het, -C(S)-C 1-10 -Alkyl group, -C(S)-(CH2) 1-6 -C 3-7 -cycloalkyl group, -C(S)-O-(CH2) 0-6 -aryl group, -C(S)-(CH2) 0-6 -O-fluorenyl group, -C(S)-NH-(CH2) 0-6 -aryl group, -C(S)-(CH2) 0-6 -aryl group or -C(S)-(CH) 1-6-het, where each alkyl group, cycloalkyl group and aryl group is unsubstituted or substituted, or optionally R 13 and R 14 forms het with the nitrogen atom, R 13 and R 14 The substituents of the alkyl group of the formula (I) are unsubstituted or substituted, and when substituted, are substituted with one or more substituents, and the substituents are selected from the group consisting of C 1-10 -Alkyl group, halogen, OH, -OC 1-6 -Alkyl group, -SC 1-6 -alkyl and -CF3, and R 13 and R 14 The substituted phenyl or aryl group is substituted with one or more substituents, and the substituents are selected from the group consisting of halogen, hydroxyl, C 1-4 -Alkyl group, C 1-4 -Alkoxy group, nitro group, -CN, -OC(O)-C 1-4 -Alkyl and -C(O)-OC 1-4 -aryl group, or a pharmaceutically acceptable salt or hydrate thereof.

[0350] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E30, E30a, E30b, E30c or E30d, [ka] Here, in E30, E30a, E30b, E30c and E30d, R 1 is selected from hydrogen or an alkyl group, R 2 is selected from hydrogen or an alkyl group, R 3 is selected from hydrogen, an alkyl group, a cycloalkyl group, or a heterocycloalkyl group; R 5 and R 6are each independently selected from hydrogen, an alkyl group, a cycloalkyl group, or a heterocycloalkyl group, or R 5 , R 6 form, together with the atoms connected thereto, a pyrrolidinyl group or a piperidine ring, and are optionally fused with one to two cycloalkyl groups, heterocycloalkyl groups, aryl groups, or heteroaryl rings, and each of the rings is further optionally fused to another cycloalkyl group, heterocycloalkyl group, aryl group, or heteroaryl ring; or R 5 and R 3 form a 5- to 8-membered ring together with the atoms connected thereto, and are optionally fused with one or two cycloalkyl groups, heterocycloalkyl groups, aryl groups, or heteroaryl rings; R 4 is selected from alkyl groups, cycloalkyl groups, heterocycloalkyl groups, cycloalkylalkyl groups, heterocycloalkylalkyl groups, aryl groups or bicyclic aryl groups, arylalkyl groups, heteroaryl groups or bicyclic heteroaryl groups, or heteroarylalkyl groups, and is further optionally substituted by 1 to 3 alkyl groups, cycloalkyl groups, heterocycloalkylalkyl groups, cycloalkylalkyl groups, heterocycloalkylalkyl groups, aryl groups or bicyclic aryl groups, arylalkyl groups, heteroaryl groups or bicyclic heteroaryl groups, or heteroarylalkyl groups.

[0351] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E31, [ka] wherein, in the above E31, A1 and A2 are each independently selected from an optionally substituted monocyclic ring, a fused ring, an aryl group, and a heteroaryl group; R is selected from H or Me.

[0352] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E32, [ka] Here, in the above E32, R 1 is selected from alkyl, cycloalkyl and heterocycloalkyl groups, and most preferably isopropyl, tert-butyl, cyclohexyl and tetrahydropyranyl groups; R 2 is selected from -OPh or H.

[0353] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E33, [ka] Here, in the above E33, R 1 is selected from H, -CH2OH, -CH2CH2OH, -CH2NH2, -CH2CH2NH2, X is selected from S or CH2; n is 1, 2 or 3; R 2 teeth, [ka] Selected from R 3 and R 4 is independently selected from H or Me.

[0354] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E34, [ka] Here, in the above E34, R 1 is selected from H or Me; R 2 is H or [ka] Selected from.

[0355] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E35, [ka] Here, in the above E35, R 1 teeth, [ka] Selected from R 2 teeth, [ka] Selected from.

[0356] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E36, [ka] Here, in the above E36, n is 0, 1 or 2, preferably 2; Z is absent or O; R 1 teeth, [ka] Selected from [ka] R in 10 is selected from hydrogen, an alkyl group, or an aryl group; X is selected from CH2 and O, and [ka] is a nitrogen-containing heteroaryl group.

[0357] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E37, [ka] Here, in the above E37, Z is absent or O; R 3 and R 4 are independently selected from H or Me; R 1 teeth, [ka] Selected from [ka] R in 10 is selected from H, an alkyl group, or an aryl group; [ka] wherein X is selected from CH2 and O, and [ka] in [ka] is a nitrogen-containing heteroaryl group.

[0358] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E38, [ka] Here, in the above E38, Z is absent or O; R 1 teeth, [ka] Selected from [ka] R in 10 is selected from H, an alkyl group, or an aryl group; [ka] wherein X is selected from CH2 and O, and [ka] in [ka] is a nitrogen-containing heteroaryl group, and R 2 is selected from H, an alkyl group, or an acyl group.

[0359] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E39, [ka] Here, in the above E39, R 2 is selected from alkyl groups, cycloalkyl groups and heterocycloalkyl groups, more preferably isopropyl groups, tert-butyl groups, cyclohexa groups and tetrahydropyranyl groups, and most preferably is cyclohexa groups; [ka] is a 5- or 6-membered nitrogen-containing heteroaryl group, more preferably a 5-membered nitrogen-containing heteroaryl group, and most preferably thiazole; and Ar is an aryl or heteroaryl group.

[0360] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E40, [ka] Here, in the above E40, R 1 is a halogen (e.g., fluorine), a cyano group, [ka] Selected from X is selected from O or CH2; In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E41, [ka] Here, in the above E41, R is selected from alkyl groups, aryl groups, heteroaryl groups, arylalkyl groups, heteroarylalkyl groups, or halogen (variable substitution positions).

[0361] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E42, [ka] Here, in the above E42, [ka] is a 6-membered nitrogen-containing heteroaryl group.

[0362] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E43, [ka] wherein, in the above E43, X is selected from CH2, O, NH or S.

[0363] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E44, E44a or E44b, [ka] Here, in the above E44, E44a and E44b, n is 1 or 2, R 2 , R 3 and R 4 are independently selected from H or a methyl group; X is independently selected from O or S; and R 1 teeth, [ka] Selected from.

[0364] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E45, [ka] Here, in the above E45, R 3 and R 4 are each independently selected from hydrogen or a methyl group; [ka] teeth, [ka] is a five-membered heterocycle selected from

[0365] In one preferred embodiment of the compound of formula I of the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is E46 or E46a, [ka] where: R 1 teeth, [ka] Selected from R 2 is selected from H or a methyl group, n is selected from 0, 1 or 2.

[0366] In one preferred embodiment of the compounds of formula I of the present invention, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharmaceutically acceptable salts thereof, E is CRBN: [ka] [ka] VHL: [ka] [ka] MDMA: [ka] IAP: [ka] [ka] [ka] [ka] [ka] [ka] is.

[0367] Preferably, in certain embodiments of the present invention, the compound of formula I above is as follows: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0368] Preferably, in certain embodiments of the present invention, the compound of formula I above is as follows: [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0369] In certain embodiments, the deuterated product is a compound structure (e.g., L, e.g., ring A, ring B, L3, ring C in LA, LA-1, LA-2, LA-3, LA-4, LA-5) in which 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 H atoms are replaced with deuterium. In certain embodiments, the deuterated LA structure is [ka] is.

[0370] In certain embodiments, the deuterated compound has any one of the following structures: [ka]

[0371] The present invention provides methods for preparing compounds of Formula I, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof.

[0372] The present invention provides pharmaceutical compositions comprising a therapeutically effective amount of a compound of Formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

[0373] The present invention provides a method for degrading SOS1 protein, the method comprising contacting SOS1 protein with a compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof.

[0374] The present invention provides compounds of formula I above, and / or their stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or their use as medicaments for treating or preventing SOS1-mediated diseases or conditions.

[0375] The present invention provides the application of the compound of the above formula I, and / or its stereoisomer, enantiomer, diastereomer, deuterated form, hydrate, solvate, metabolite, prodrug and / or pharmaceutically acceptable salt thereof, or pharmaceutical composition thereof, as a drug for treating or preventing a disease or condition (cancer) caused by the interaction between SOS1 and Ras (e.g., KRAS) or SOS1 and Rac (e.g., KRAS).

[0376] The present invention provides the application of a compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the manufacture of a medicament for treating or preventing an SOS1-mediated disease or condition (e.g., cancer).

[0377] The present invention provides the application of a compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the manufacture of a medicament for treating or preventing a disease or condition (e.g., cancer) caused by the interaction between SOS1 and Ras (e.g., KRAS) or SOS1 and Rac (e.g., KRAS).

[0378] The present invention provides the application of a compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the manufacture of a medicament for treating or preventing cancer.

[0379] The present invention provides the application of a compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated form, hydrate, solvate, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, in the manufacture of a medicament for treating or preventing pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, diffuse large B-cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular carcinoma, breast cancer, ovarian cancer, prostate cancer, glioblastoma, kidney cancer and sarcoma.

[0380] The present invention provides the application of the compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated form, hydrate, solvate, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, in the manufacture of a medicament for treating or preventing neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), capillary malformation-arteriovenous malformation syndrome (CM-AVM), Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Regius syndrome and hereditary gingival fibromatosis.

[0381] The present invention provides a method for treating or preventing an SOS1-mediated disease or condition, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof.

[0382] The present invention provides methods for treating or preventing a disease or condition (e.g., cancer) that is modulated by the interaction of SOS1 and Ras (e.g., KRAS) or SOS1 and Rac (e.g., KRAS), comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof.

[0383] In certain embodiments of the present invention, the cancer is Heart: sarcomas (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma, Lung: bronchial cancer (squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, adenocarcinoma), alveolar carcinoma (bronchiolar carcinoma), bronchial adenoma, sarcoma, lymphoma, chondroma, hamartoma, mesothelioma, Gastrointestinal esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vasoactive intestinal peptide tumor), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma), Urinary system: kidney (adenocarcinoma, nephroblastoma, lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (spermatogonoma, teratoma, embryonal carcinoma, teratoma, choriocarcinoma, sarcoma, mesenchymal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma), Liver: liver cancer (hepatocellular carcinoma), bile duct cancer, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma, Biliary tract: gallbladder cancer, ampulla cancer, bile duct cancer, Bone: osteosarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, chondroma (osteochondral exogenous bone disease), benign chondroma, chondroblastoma, chondromyxoid fibroma, osteoid osteoma and giant cell tumor, Nervous system: skull (osteoma, hemangioma, granuloma, xanthomas, osteitis teratoides), meninges (meningioma, meningeal sarcoma, glioma), brain (astrocytoma, medullary blastoma, glioma, ependymoma, germ cell tumor (pineal tumor), glioblastoma multiforme, oligodendroglioblastoma, schwannoma, retinoblastoma, congenital tumor), spinal cord neurofibroma, meningioma, glioma, sarcoma), Gynecology: Uterus (endometrial cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-theca cell tumor, Sertoli stromal cell tumor, germ cell abnormality, malignant teratoma), vulva (squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma), fallopian tube (cancer), Hematology: Blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma), Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevus, lipoma, hemangioma, dermatofibroma, keloid, psoriasis, Adrenal gland: May be selected from neuroblastoma.

[0384] In certain embodiments of the invention, the cancer may be selected from pancreatic cancer, lung cancer, colorectal cancer, cholangiothelial cancer, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, squamous cell carcinoma of the head and neck, diffuse large B-cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular carcinoma, breast cancer, ovarian cancer, prostate cancer, glioblastoma, renal cancer, and sarcoma.

[0385] The present invention further provides the application of the compound of formula I above, and / or its stereoisomer, enantiomer, diastereomer, deuterated form, hydrate, solvate, prodrug and / or pharmaceutically acceptable salt thereof, or the pharmaceutical composition above, in the manufacture of a medicament for treating and / or preventing a KRAS-mediated disease or condition.

[0386] The present invention further provides a method for treating and / or preventing a KRAS-mediated disease or condition, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof.

[0387] In a specific embodiment of the present invention, the KRAS may be a mutant KRAS, preferably one or more of KRAS G12C, KRAS G12D, KRAS G13D, and KRAS G12V.

[0388] The present invention provides a process for preparing a compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, metabolites, prodrugs and / or pharmaceutically acceptable salts thereof: S is S6c [ka] and L is LA [ka] and ring B contains an NH group, the preparation method is as follows: [ka] INT-A is subjected to reductive amination with INT-B to obtain the target compound, wherein the reducing reagent for the reductive amination includes, but is not limited to, Pd / C, sodium borohydride, sodium cyanoborohydride, borane, and sodium triacetoxyborohydride. [ka] refers to ring B containing the NH group, and R2, R3, R4, R5, R6, R7 are as defined and explained in S6b; [ka] refers to L3 containing an aldehyde group, wherein ring A, ring B, ring C, and X″ are as defined in L A, and E is as defined and explained in the present invention, and E is preferably E7, E7a, E7b, E7c, E7d, E7e, E7a-1, E7a-2, E21, E21-1a, E21-1b, E21-1c, E21-1d, E21-1e, E21-1f, E21-1g, E21-1h, E21-1aa, E21-1bb, E21-1cc, E21-1dd, E21-1ee, E21-1ff, E21-1gg, or E21-1hh.

[0389] S is S6c [ka] and L is LA [ka] and ring C contains an NH group and X″ is C(O), the preparation method is as follows: [ka] The target compound is obtained by a substitution reaction between INT-C and INT-D under basic conditions, where the base includes, but is not limited to, triethylamine, N,N-diisopropylethylamine, potassium carbonate, sodium carbonate, and sodium bicarbonate. [ka] refers to the ring C containing the NH group, and P 100is a pentafluorophenyl group or a p-nitrophenyl group, R2, R3, R4, R5, R6, R7 are as defined and explained in S6b, ring A, ring B, ring C, L3 are as defined in L-A, E is as defined and explained in the present invention, and E is preferably E7, E7a, E7b, E7c, E7d, E7e, E7a-1, E7a-2, E21, E21-1a, E21-1b, E21-1c, E21-1d, E21-1e, E21-1f, E21-1g, E21-1h, E21-1aa, E21-1bb, E21-1cc, E21-1dd, E21-1ee, E21-1ff, E21-1gg or E21-1hh.

[0390] S is S6d [ka] and L is LA [ka] and ring C contains an NH group and X″ is C(O), the preparation method is as follows: [ka] The target compound is obtained by a substitution reaction between INT-E and INT-D under basic conditions, where the base includes, but is not limited to, triethylamine, N,N-diisopropylethylamine, potassium carbonate, sodium carbonate, and sodium bicarbonate. [ka] refers to the ring C containing the NH group, and P 100is a pentafluorophenyl group or a p-nitrophenyl group, R2, R3, R4, R5, R6, R7 are as defined and explained in S6d, ring A, ring B, ring C, L3 are as defined in L-A, E is as defined and explained in the present invention, and E is preferably E7, E7a, E7b, E7c, E7d, E7e, E7a-1, E7a-2, E21, E21-1a, E21-1b, E21-1c, E21-1d, E21-1e, E21-1f, E21-1g, E21-1h, E21-1aa, E21-1bb, E21-1cc, E21-1dd, E21-1ee, E21-1ff, E21-1gg or E21-1hh.

[0391] DETAILED DESCRIPTION: Unless stated to the contrary, the following terms used in the specification and claims have the following meanings.

[0392] The term "alkyl group" refers to a saturated aliphatic hydrocarbon group including a straight-chain or branched-chain alkyl group, and examples of the C1-C8 alkyl group include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylpropyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylpropyl, 2-methylpropyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-hexyl, 2-methylpropyl, 2-methylpentyl ... and alkyl groups having 1 to 8 carbon atoms, such as n-octyl, 2,3-dimethylhexyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, or various branched chain isomers thereof, preferably C1-C6 alkyl groups, more preferably C1-C4 alkyl groups. The alkyl groups may be substituted or unsubstituted. In some embodiments, the alkyl group is a C1, C2, C3, C4, C5, C6, C7, or C8 alkyl group.

[0393] "Cycloalkyl group" means a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, and is defined as "C3-C 11 A "C3-C8 membered cycloalkyl group" is a cycloalkyl group containing 3 to 11 carbon atoms, a "C3-C8 membered cycloalkyl group" is a cycloalkyl group containing 3 to 8 carbon atoms, and a "C5-C 10"membered cycloalkyl group" is a cycloalkyl group containing 5 to 10 carbon atoms, Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexa, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl groups, etc., preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexa, and C3-C8 membered cycloalkyl groups, more preferably C3-C6 membered cycloalkyl groups.

[0394] Polycyclic cycloalkyl groups include spirocyclic, fused-ring, and bridged-ring cycloalkyl groups. A "spirocycloalkyl group" refers to a polycyclic group in which the single rings share one carbon atom (called a spiro atom), and may contain one or more double bonds, but none of the rings has a fully conjugated π-electron system. Depending on the number of spiro atoms shared between the rings, spirocycloalkyl groups are classified as monospirocycloalkyl groups, bisspirocycloalkyl groups, or polyspirocycloalkyl groups, with 7- to 12-membered bisspirocycloalkyl groups being preferred. Non-limiting examples of spirocycloalkyl groups include: [ka] Includes.

[0395] "Fused cycloalkyl group" refers to an all-carbon polycyclic group in which each ring in the system shares an adjacent pair of carbon atoms with another ring in the system, and one or more rings may contain one or more double bonds, but none of the rings has a completely conjugated π-electron system. Depending on the number of rings, fused cycloalkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic, with bicyclic fused cycloalkyl groups being preferred. Non-limiting examples of fused cycloalkyl groups include: [ka] Includes.

[0396] "Bridged cycloalkyl group" refers to an all-carbon polycyclic group in which any two rings share two carbon atoms that are not directly connected, and may contain one or more double bonds, but no ring has a completely conjugated pi-electron system, and can be divided into bicyclic, tricyclic, tetracyclic, or polycyclic bridged cycloalkyl groups depending on the number of rings they contain. Non-limiting examples of bridged cycloalkyl groups include: [ka] The cycloalkyl ring may be fused to an aryl group, a heteroaryl group, or a heterocycloalkyl ring, where the ring connected to the parent structure is a cycloalkyl group ring, non-limiting examples include indanyl, tetrahydronaphthyl, benzocycloheptanyl, etc. The cycloalkyl group may be optionally substituted or unsubstituted.

[0397] In some embodiments, the cycloalkyl group is selected from the group consisting of C, ... 10 , C 11 , C 12 Mono- or polycyclic (eg, spirocyclic, fused or bridged) cycloalkyl groups.

[0398] A "heterocycloalkyl group" is a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent in which one or more (e.g., 2, 3, 4, or 5) ring atoms are nitrogen, oxygen, or S(O). r (where r is an integer of 0, 1, or 2), but does not contain a ring portion of -OO-, -OS-, or -SS-, and the remaining ring atoms are carbon. A "3- to 11-membered heterocycloalkyl group" is a cyclyl group containing 3 to 11 ring atoms, a "5- to 10-membered heterocycloalkyl group" is a cyclyl group containing 5 to 10 ring atoms, and a "3- to 8-membered heterocycloalkyl group" is a cyclyl group containing 3 to 8 ring atoms, preferably a "3- to 11-membered heterocycloalkyl group" containing 1 to 2 heteroatoms selected from N, O, or S, and more preferably a 3- to 11-membered heterocycloalkyl group containing 1 or 2 N atoms.

[0399] The monocyclic heterocycloalkyl group is preferably a 3- to 8-membered monocyclic heterocycloalkyl group containing 1 to 2 N heteroatoms, and non-limiting examples of the monocyclic heterocycloalkyl group include a pyrrolidinyl group, a piperidinyl group, a piperazinyl group, a morpholinyl group, a thiomorpholinyl group, a homopiperazinyl group, etc., and preferably a piperidinyl group or a piperazinyl group.

[0400] Polycyclic heterocycloalkyl groups include spirocyclic, fused-ring, and bridged-ring heterocycloalkyl groups. A "spiroheterocycloalkyl group" is a polycyclic heterocycloalkyl group that shares one atom (called a spiroatom) between the rings, one or more of which ring atoms are nitrogen, oxygen, or S(O). r (where r is an integer selected from 0, 1, and 2), and the remaining ring atoms are carbon. They may contain one or more double bonds, but none of the rings has a completely conjugated π-electron system. Spirocycloalkyl groups are classified as monospiroheterocycloalkyl groups, bisspiroheterocycloalkyl groups, or polyspiroheterocycloalkyl groups depending on the number of spiro atoms shared between the rings. Spirocycloalkyl groups are preferably saturated "3- to 11-membered bisspiroheterocycloalkyl groups" containing 1 to 2 heteroatoms selected from N, O, or S, and more preferably saturated "7- to 11-membered bisspiroheterocycloalkyl groups" containing 1 or 2 N atoms. Non-limiting examples of spiroheterocycloalkyl groups include: [ka]

[0401] A "fused heterocycloalkyl group" is a polycyclic heterocycloalkyl group in which each ring in the system shares an adjacent pair of atoms with another ring in the system, one or more rings optionally containing one or more double bonds, but none of the rings has a completely conjugated pi-electron system, and one or more of the ring atoms is nitrogen, oxygen, or S(O). r(where r is an integer selected from 0, 1, and 2), and the remaining ring atoms are carbon. Depending on the number of rings constituting the heterocycloalkyl group, it can be divided into bicyclic, tricyclic, tetracyclic, and polycyclic fused heterocycloalkyl groups, and is preferably a "3- to 11-membered bicyclic fused heterocycloalkyl group" containing 1 to 3 heteroatoms selected from N, O, and S, and more preferably a saturated "3- to 11-membered bicyclic fused heterocycloalkyl group" containing 1 or 2 N atoms. Non-limiting examples of fused heterocycloalkyl groups include the following: [ka]

[0402] A "bridged heterocycloalkyl group" is a polycyclic heterocycloalkyl group in which any two rings share two atoms that are not directly connected, and may contain one or more double bonds, but none of the rings has a completely conjugated pi-electron system, and one or more of the ring atoms is nitrogen, oxygen, or S(O). r (wherein r is an integer selected from 0, 1, and 2), and the remaining ring atoms are carbon. Depending on the number of rings, bridged cycloalkyl groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic. Non-limiting examples of bridged heterocycloalkyl groups include the following: [ka]

[0403] The heterocycloalkyl group ring may be fused to an aryl group, heteroaryl group, or cycloalkyl group ring, where the ring connected to the parent structure is a heterocycloalkyl group ring, non-limiting examples include: [ka] wherein the heterocycloalkyl group may be optionally substituted or unsubstituted.

[0404] In some embodiments, the heterocycloalkyl group is a 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered monocyclic or polycyclic (e.g., spirocyclic, fused, or bridged) heterocycloalkyl group, wherein the number of heteroatoms can be 1, 2, 3, 4, or 5, and each heteroatom is independently nitrogen, oxygen, or S(O). r (where r is an integer 0, 1, or 2).

[0405] An "aryl group" is an all-carbon monocyclic or fused polycyclic (i.e., rings that share adjacent pairs of carbon atoms) polycyclic group having a conjugated π-electron system, and a "6- to 10-membered aryl group" is an all-carbon aryl group containing 6 to 10 carbons, such as phenyl and naphthyl, preferably phenyl. The aryl ring may be fused to a heteroaryl, heterocycloalkyl, or cycloalkyl ring, where the ring connected to the parent structure is an aryl ring; non-limiting examples include: [ka] wherein the aryl group may be optionally substituted or unsubstituted. In some embodiments, the aryl group is a 6- to 10-membered aryl group.

[0406] A "heteroaryl group" is a heteroaromatic system containing 1 to 4 heteroatoms, the heteroatoms being nitrogen, oxygen, or S(O). r(where r is an integer 0, 1, or 2), the 5- to 6-membered heteroaryl group is a heteroaromatic system containing 5 to 6 ring atoms, and the 5- to 10-membered heteroaryl group is a heteroaromatic system containing 5 to 10 ring atoms, preferably a 5- to 6-membered heteroaryl group, more preferably a 5- to 6-membered heteroaryl group containing one or two N atoms, non-limiting examples include furan, thienyl, pyridyl, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, pyrazole, imidazolyl, triazolyl, tetrazolyl, etc., preferably a pyridyl group. The heteroaryl ring may be fused to an aryl, heterocycloalkyl, or cycloalkyl ring, in which the ring connected to the parent structure is a heteroaryl ring, non-limiting examples include [ka] In some embodiments, the heteroaryl group is a 5-, 6-, 7-, 8-, 9-, or 10-membered heteroaryl group, where the number of heteroatoms can be 1, 2, 3, 4, or 5, and each heteroatom is independently nitrogen, oxygen, or sulfur.

[0407] An "alkenyl group" is an alkyl group as defined above that is composed of at least two carbon atoms and at least one carbon-carbon double bond. A "C2-8 alkenyl group" is a straight-chain or branched alkenyl group containing 2 to 8 carbon atoms, including, but not limited to, vinyl, 1-propenyl, 2-propenyl, 1-, 2-, or 3-butenyl groups. Preferably, it is a "C2-6 alkenyl group," and more preferably a "C2-4 alkenyl group." The alkenyl group may be substituted or unsubstituted. In some embodiments, the alkenyl group is a C2, C3, C4, C5, C6, C7, or C8 alkenyl group.

[0408] An "alkynyl group" is an alkyl group as defined above that is composed of at least two carbon atoms and at least one carbon-carbon triple bond. A "C2-8 alkynyl group" is a straight- or branched-chain alkynyl group containing 2 to 8 carbon atoms, including, but not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-, 2-, or 3-butynyl. Preferably, it is a "C2-6 alkynyl group," and more preferably, it is a "C2-4 alkynyl group." The alkynyl group may be substituted or unsubstituted. In some embodiments, the alkynyl group is a C2, C3, C4, C5, C6, C7, or C8 alkynyl group.

[0409] "Subunit" refers to a divalent group, for example, alkylene group refers to a divalent alkyl group, alkenylene group refers to a divalent alkenyl group, alkynylene group refers to a divalent alkynyl group, cycloalkylene group refers to a divalent cycloalkyl group, heterocycloalkylene group refers to a divalent heterocycloalkyl group, arylene group refers to a divalent aryl group, and heteroarylene group refers to a divalent heteroaryl group, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are as defined above, and the subunits may be optionally substituted or unsubstituted.

[0410] "Haloalkyl group" refers to an alkyl group optionally substituted with one or more fluorine, chlorine, bromine, or iodine atoms, wherein said alkyl group is as defined above, and non-limiting examples include, but are not limited to, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, and the like. "Hydroxyalkyl group" refers to an alkyl group optionally substituted with one or more -OH groups, wherein said alkyl group is as defined above, and non-limiting examples include, but are not limited to, hydroxymethyl, hydroxyethyl, hydroxypropyl, and hydroxyisopropyl groups.

[0411] "Alkoxy" refers to an --O-alkyl group, wherein said alkyl group is as defined above, and non-limiting examples include methoxy, ethoxy, isopropoxy, tert-butoxy, and the like.

[0412] "Cycloalkoxy" refers to an -O-cycloalkyl group, wherein the cycloalkyl group is as defined above, and non-limiting examples include cyclopropanyloxy, cyclobutanyloxy, cyclopentanyloxy, cyclohexanyloxy, and the like.

[0413] "Heterocycloalkoxy" refers to an -O-heterocycloalkyl group, wherein said heterocycloalkyl group is as defined above, and non-limiting examples include azacyclobutanyloxy, azacyclopentanyloxy, piperidinyloxy, piperazinyloxy, oxolanyloxy, oxanyloxy, and the like.

[0414] "-C(O)C1-C3 alkyl group" refers to -C(O)-CH3, -C(O)-CH2CH3, and the like.

[0415] A "cyano group" refers to -CN.

[0416] A "hydroxy group" refers to -OH.

[0417] A "sulfonyl group" refers to -S(O)2-.

[0418] A "carboxy group" or a "carboxylic acid" refers to -COOH.

[0419] "Oxo" refers to the group =O.

[0420] "Halogen" refers to fluorine, chlorine, bromine or iodine.

[0421] "Pd(PPh3)2Cl2" refers to (dichlorobis(triphenylphosphino)palladium).

[0422] "TEA" refers to triethylamine.

[0423] "EA or EtOAc" refers to ethyl acetate.

[0424] "THF" refers to tetrahydrofuran.

[0425] "NaBH4" refers to sodium borohydride.

[0426] "DCM" refers to dichloromethane;

[0427] "TfO" refers to trifluoromethanesulfonic anhydride

[0428] "(Bpin)2" refers to bis(pinacolato)diboron.

[0429] "Pd(dppf)2Cl2" refers to 1,1'-bisdiphenylphosphinoferrocenedichloropalladium.

[0430] "KOAc" refers to potassium acetate.

[0431] "DMF" refers to N,N-dimethylformamide.

[0432] "NBS" refers to N-bromosuccinimide.

[0433] "EtOH" refers to ethanol.

[0434] "MeOH" refers to methanol.

[0435] "Pd / C" refers to palladium on carbon.

[0436] "Pd(OH)2 / C" refers to palladium hydroxide on carbon.

[0437] "DMSO" refers to dimethyl sulfoxide.

[0438] "HATU" refers to 2-(7-azobenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0439] "TFA" refers to trifluoroacetic acid.

[0440] "NMP" refers to N-methylpyrrolidone.

[0441] "IBX" refers to 2-iodoxybenzoic acid.

[0442] "DIEA" refers to N,N-diisopropylethylamine.

[0443] "STAB" refers to sodium triacetoxyborohydride.

[0444] "T3P" refers to 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide.

[0445] "NaOH" refers to sodium hydroxide.

[0446] "DMAP" refers to 4-dimethylaminopyridine.

[0447] "TPSCl" refers to 2,4,6-triisopropylbenzenesulfonyl chloride.

[0448] "DPBS" refers to Duchenne phosphate buffered saline.

[0449] "Dess-Martin" refers to the Dess-Martin reagent.

[0450] "PBS" refers to phosphate buffered saline;

[0451] "SDS-PAGE" refers to sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

[0452] "PVDF" refers to polyvinylidene fluoride.

[0453] "PE" refers to petroleum ether.

[0454] "NaHCO3" refers to sodium bicarbonate.

[0455] "Na2SO4" refers to sodium sulfate.

[0456] "NH4Cl" refers to ammonium chloride.

[0457] "AcOH" refers to acetic acid.

[0458] "HCl" refers to hydrochloric acid.

[0459] "DCC" refers to N,N'-dicyclohexacarbodiimide.

[0460] "Ti(OEt)4" refers to titanium ethoxide.

[0461] "L-Selectride" refers to lithium tri(sec-butyl)borohydride.

[0462] "BOP" refers to (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate.

[0463] "DBU" refers to 1,8-diazacyclo[5,4,0]undecene-7.

[0464] "LiOH.H2O" refers to lithium hydroxide monohydrate.

[0465] "EDCI" refers to 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[0466] "NIS" refers to N-iodosuccinimide.

[0467] "Ac2O" refers to acetic anhydride.

[0468] "HOAc" refers to acetic acid.

[0469] "Hantzsch-ester" refers to diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate.

[0470] "DMA" refers to dimethylacetamide.

[0471] "NiBr2(dtbpy)" refers to 4,4'-di-tert-butylbipyridine nickel dibromide.

[0472] "K2CO3" refers to potassium carbonate.

[0473] "9-BBN" refers to 9-borabicyclo[3.3.1]nonane.

[0474] "MTBE" refers to methyl tert-butyl ether.

[0475] "LiOH" refers to lithium hydroxide.

[0476] "DCE" refers to dichloroethane.

[0477] "NaBH3CN" refers to sodium cyanoborohydride.

[0478] "CBr4" refers to carbon tetrabromide.

[0479] "PPh3" refers to triphenylphosphine

[0480] "n-BuLi" refers to n-butyllithium.

[0481] "NaH" refers to sodium hydride.

[0482] "i-PrOH" refers to isopropyl alcohol.

[0483] "ACN" refers to acetonitrile.

[0484] "NH4HCO3" refers to ammonium bicarbonate.

[0485] "m-CPBA" refers to m-chloroperoxybenzoic acid.

[0486] "KI" refers to potassium iodide.

[0487] "IPA" refers to isophthalic acid.

[0488] "N2H4-H2O" refers to hydrazine hydrate.

[0489] "NMI" refers to N-methimidazole.

[0490] "TCFH" refers to fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate.

[0491] "Ruphos Pd G2" refers to chloro(2-dicyclohexylphosphino-2',6'-di-isopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II).

[0492] "K3PO4" refers to potassium phosphate.

[0493] "(Boc)2O" refers to di-tert-butyl dicarbonate.

[0494] "Prep-HPLC" refers to preparative high performance liquid chromatography.

[0495] "Sat." refers to a saturated solution.

[0496] "aq" refers to an aqueous solution.

[0497] In the chemical structures herein, a bond "-" indicates a single bond, and an "=" indicates a double bond (which may be trans or cis, unless the configuration is limited).

[0498] "Optionally" means that the subsequently described event or circumstance may, but does not necessarily, occur, and the description includes cases where the event or circumstance occurs and cases where it does not. For example, "a heterocycloalkyl group optionally substituted with an alkyl group" means that the alkyl group may, but does not necessarily, be present, and the phrase includes cases where the heterocycloalkyl group is substituted with an alkyl group and cases where the heterocycloalkyl group is not substituted with an alkyl group. The term "substituted" refers to one or more hydrogen atoms in a group, preferably 5 or less, more preferably 1 to 3 hydrogen atoms, being independently replaced with the corresponding number of substituents. Of course, the substituents are located only at their chemically feasible positions, and those skilled in the art can easily determine (by experiment or theory) possible or impossible substitutions. For example, an amino group or a hydroxy group having free hydrogen may be unstable when bonded to a carbon atom having an unsaturated (e.g., olefinic) bond. Unless otherwise specified, the term "optionally substituted" as used herein may mean unsubstituted or substituted, and when substituted, the substituents may be independently one or more (e.g., 2, 3, 4, 5, or 6) selected from alkyl groups, alkenyl groups, alkynyl groups, hydroxy groups, hydroxyalkyl groups, haloalkyl groups, alkoxy groups, amino groups, aminoalkyl groups, cyano groups, halogens, oxo, cycloalkyl groups, heterocycloalkyl groups, aryl groups, and heteroaryl groups, and the alkyl groups, alkenyl groups, alkynyl groups, hydroxy groups, hydroxyalkyl groups, haloalkyl groups, alkoxy groups, amino groups, aminoalkyl groups, cyano groups, halogens, oxo, cycloalkyl groups, heterocycloalkyl groups, aryl groups, and heteroaryl groups. The hydroxyalkyl, haloalkyl, alkoxy, amino, and aminoalkyl groups are optionally substituted with one or more (e.g., 2, 3, 4, 5, or 6) cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups, and the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are optionally substituted with one or more groups selected from alkyl, alkenyl, alkynyl, hydroxy, hydroxyalkyl, haloalkyl, alkoxy, amino, aminoalkyl, cyano, halogen, and oxo.

[0499] A "pharmaceutical composition" refers to a mixture of one or more compounds described herein or physiologically / pharmaceutically acceptable salts or prodrugs thereof with other chemical components, and other components such as physiologically / pharmaceutically acceptable carriers and excipients. The pharmaceutical composition is intended to facilitate administration to a living body and contribute to the absorption of the active ingredients to further exert their biological activity.

[0500] The present invention further provides pharmaceutically acceptable salts of compounds of Formula (I). The term "pharmaceutically acceptable salts" refers to acid or base addition salts of the relatively non-toxic compounds of the present invention. The acid addition salts are salts formed with the compounds of Formula (I) of the present invention and suitable inorganic or organic acids. These salts may be prepared during the final isolation and purification process of the compounds, or by reacting the purified compounds of Formula (I) in their free base form with a suitable organic or inorganic acid. Representative acid addition salts include hydrobromide, sulfate, bisulfate, sulfite, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, hydrogenphosphate, carbonate, bicarbonate, toluate, citrate, maleate, fumarate, succinate, methanesulfonate, p-toluenesulfonate, gluconate, lactobionate, and laurylsulfonate. The base addition salts are salts formed between the compounds of formula (I) and suitable inorganic or organic bases, including salts formed with basic metals, basic earth metals, and quaternary ammonium cations, such as sodium salts, lithium salts, potassium salts, calcium salts, magnesium salts, tetramethylquaternary ammonium salts, and tetraethylquaternary ammonium salts; and amine salts include salts formed with ammonia (NH), primary amines, secondary amines, or tertiary amines, such as methylamine salts, dimethylamine salts, trimethylamine salts, triethylamine salts, and ethylamine salts.

[0501] The compounds of the present invention, or pharmaceutically acceptable salts thereof, can be administered to mammals, including humans, orally, rectally, topically (intravenously, intramuscularly, or subcutaneously), locally (as powders, ointments, or drops), or intratumorally.

[0502] The dosage of the compound of the present invention may be about 0.05 to 300 mg / kg body weight / day, preferably 10 to 300 mg / kg body weight / day, and more preferably 10 to 200 mg / kg body weight / day.

[0503] The compounds of the present invention or pharmaceutically acceptable salts thereof can be formulated into solid dosage forms for oral administration, including, but not limited to, capsules, tablets, pills, powders, granules, etc. In these solid dosage forms, the compounds of formula (I) of the present invention are mixed as an active ingredient with at least one conventional inert excipient (or carrier), for example, sodium citrate or dicalcium phosphate, or the following ingredients: (1) a filler or solubilizer such as starch, lactose, sucrose, glucose, mannitol, and silicic acid, (2) a binder such as hydroxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and gum arabic, (3) a humectant such as glycerin, and (4) agar. The capsules, tablets, and pills may contain buffering agents, such as (1) disintegrants such as calcium carbonate, potato starch or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate, (2) solubilizers such as paraffin, (3) absorption promoters such as quaternary ammonium compounds, (4) wetting agents such as cetyl alcohol and glyceryl monostearate, (5) adsorbents such as kaolin, and (6) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, and sodium lauryl sulfate, or mixtures thereof.

[0504] The above solid dosage forms, such as tablets, sugar-coated tablets, capsules, pills, and granules, can be coated or microencapsulated with coating and shell materials, such as enteric coatings, and other materials well known in the art. They may also contain opacifying agents, so that the release of the active ingredient in such compositions can be delayed in a specific part of the digestive tract. Examples of embedding materials that can be used include polymeric substances and wax-based materials. If necessary, the active ingredient can be formed into a microencapsulated form with one or more of the above-mentioned excipients.

[0505] The compounds of the present invention or their pharmaceutically acceptable salts can be formulated into liquid dosage forms for oral administration, including, but not limited to, pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and tinctures. In addition to the compound of formula (I) or its pharmaceutically acceptable salt as the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as water, and other solvents, solubilizers, and emulsifiers, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-butanediol, dimethylformamide, and oils, particularly cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, and sesame oil, or mixtures of these substances. In addition to these inert diluents, the liquid dosage forms of the present invention may contain conventional auxiliary agents, such as wetting agents, emulsifying and suspending agents, sweeteners, flavoring agents, and fragrances.

[0506] Such suspending agents include ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide, agar, and the like, or mixtures of these substances.

[0507] The compounds of the present invention or their pharmaceutically acceptable salts can be formulated into dosage forms for parenteral injection, including, but not limited to, physiologically acceptable sterile aqueous or anhydrous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable carriers, diluents, solvents or excipients include water, ethanol, polyols, and suitable mixtures thereof.

[0508] The compound of the present invention or a pharmaceutically acceptable salt thereof can also be formulated into dosage forms for topical administration, including ointments, powders, suppositories, drops, sprays, inhalants, etc. The compound of formula (I) of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient is mixed under sterile conditions with a physiologically acceptable carrier and optional preservatives, buffers, or propellants that may be required as needed.

[0509] The present invention further provides a pharmaceutical composition comprising a compound of formula (I) of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier, excipient or diluent. When preparing a pharmaceutical composition, the compound of formula (I) of the present invention or a pharmaceutically acceptable salt thereof is generally mixed with a pharmaceutically acceptable carrier, excipient or diluent.

[0510] According to conventional manufacturing methods, the above-mentioned compositions of the present invention can be manufactured into conventional pharmaceutical preparations, such as tablets, pills, capsules, powders, granules, emulsions, suspensions, dispersions, solutions, syrups, elixirs, ointments, drops, suppositories, sprays, propellants, etc.

[0511] The compounds according to the present invention or their pharmaceutically acceptable salts may be administered alone or (if necessary) in combination with other pharmaceutically acceptable therapeutic agents, such as other antitumor agents. The combined components may be administered simultaneously or sequentially in a single formulation or in different formulations. The above combinations may include a combination of a compound of the present invention with one other active agent, or may include a combination of a compound of the present invention with two or more other active agents.

[0512] In the present invention, other pharmaceutically acceptable therapeutic agents that can be used together with or in combination with the compound of formula (I) which is an SOS1 degrader include EGFR and / or mutant inhibitors thereof, ErbB2 (Her2) and / or mutant inhibitors thereof, ALK and / or mutant inhibitors thereof, MEK and / or mutant inhibitors thereof, Kras and / or mutant inhibitors thereof, BCR-ABL and / or mutant inhibitors thereof, FGFR1 / FGFR2 / FGFR3 and / or mutant inhibitors thereof, ROS1 and / or mutant inhibitors thereof, c-MET and and / or mutant inhibitors thereof, AXL and / or mutant inhibitors thereof, NTRK1 and / or mutant inhibitors thereof, RET and / or mutant inhibitors thereof, taxanes, platinum-containing compounds, antimetabolites, mitotic kinase inhibitors, immunotherapeutics, anti-angiogenic agents, topoisomerase inhibitors, A-Raf / B-Raf / C-Raf and / or mutant inhibitors thereof, ERK and / or mutant inhibitors thereof, apoptosis inhibitors, mTOR inhibitors, epigenetic modulators, IGF1 / 2 and / or IGF1-R inhibitors, Ras GEF and / or mutant inhibitors thereof, PI3K and / or mutant inhibitors thereof.

[0513] In the present invention, other pharmaceutically acceptable therapeutic agents that can be used together with or in combination with the compound of formula (I) which is an SOS1 degrader include afatinib, erlotinib, gefitinib, lapatinib, cetuximab, panitumumab, osimertinib, olmutinib, EGF-816, trastuzumab, pertuzumab, crizotinib, alectinib, and the like. b), entrectinib, brigatinib, trametinib, cobimetinib, binimetinib, selumetinib, rifatinib, imatinib, dasatinib, nilotinib, nintedanib, crizotinib, lorlatinib, ceritinib b), merestinib, paclitaxel, nab-paclitaxel, docetaxel, cisplatin, carboplatin, oxaliplatin, 5-fluorouracil, capecitabine, fluoxuridine, cytarabine, gemcitabine, trifluridine, and tipiracil ) combination (=TAS102), palbociclib, ribociclib, abemaciclib, ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, irinotecan, PDR-001 (=spartalizumab),It may be bevacizumab, pidilizumab, liposomal irinotecan, topotecan, ulixertinib, rapamycin, temsirolimus, everolimus, ridaforolimus, JQ-1, GSK 525762, OTX 015 (=MK8628), CPI 0610, TEN-010 (=RO6870810), xentuzumab (antibody 60833 of WO2010 / 066868) or MEDI-573 (=dusigitumab).

[0514] In the present invention, SOS1 kinase activity measurement experiments demonstrated that the compound of formula I described in the present invention can effectively bind to or inhibit SOS1 target protein, and Western blot demonstrated that the compound of formula I described in the present invention can effectively and specifically degrade SOS1 protein in NCI-H358 cells. The compound of formula I described in the present invention, and / or its stereoisomers, enantiomers, diastereomers, deuterated compounds, hydrates, solvates, metabolites, prodrugs, and / or pharmaceutically acceptable salts thereof, can effectively degrade SOS1 protein, thereby achieving the effects of preventing or treating diseases or conditions related to SOS1 or caused by the interaction between SOS1 and Ras or SOS1 and Rac. DETAILED DESCRIPTION OF THE INVENTION

[0515] The present invention will be described in more detail and comprehensively with reference to the following examples, but the present invention is not limited thereto. The present invention is also not limited to the contents of the examples. The starting materials in the examples of the present invention are known and commercially available, or can be synthesized by methods known in the art. Unless otherwise specified, experimental methods for which specific conditions are not specified in the examples of the present invention generally follow conventional conditions or conditions recommended by the manufacturers of raw materials or products.

[0516] I. Example of compound production

[0517] Intermediate 1: (R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl-1-amine hydrochloride

[0518] Step 1: Preparation of 1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl-1-one [ka] Under nitrogen gas protection, a reaction mixture of 1-bromo-3-nitro-5-(trifluoromethyl)benzene (18 g, 66.7 mmol), tributyl(1-ethoxyvinyl)stannane (31 g, 86.7 mmol), Pd(PPh)Cl (4.7 g, 6.67 mmol), and triethyl ether (TEA) (13.5 g, 133 mmol) in 1,4-dioxane (200 mL) was stirred at 80 °C overnight. The reaction mixture was quenched with potassium fluoride (saturated aqueous solution, 300 mL) and extracted with EA (200 mL × 3). The organic layer was collected and concentrated under reduced pressure. The concentrate was dissolved in THF (180 mL), and hydrochloric acid (100 mL, 6 M) was added. The mixture was stirred at room temperature for 3 h. The mixture was then quenched with water (300 mL) and extracted with EA (200 mL × 3). The organic layer was collected, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The material was purified by column chromatography to give the target product, 1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl-1-one. 1 H NMR(400MHz,CDCl3) δ8.95(t,J=1.6Hz,1H),8.69(s,1H),8.54(d,J=0.5Hz,1H),2.76(s,3H).

[0519] Step 2: Preparation of (R,E)-2-methyl-N-(1-(3-nitro-5-(trifluoromethyl)phenyl)ethylidene)propyl-2-sulfinamide [ka] A reaction mixture of 1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl-1-one (10.6 g, 45.5 mmol), (R)-2-methylpropyl-2-sulfinamide (8.3 g, 68.2 mmol), and titanium ethoxide (25.9 g, 114 mmol) in THF (200 mL) was stirred at 60 °C for 2 h. The reaction mixture was quenched with water (300 mL), and the solution was extracted with EA (200 mL × 3). The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the target product, (R,E)-2-methyl-N-(1-(3-nitro-5-(trifluoromethyl)phenyl)ethylidene)propyl-2-sulfinamide. 1 H NMR(400MHz,DMSO-d6) δ8.87(s,1H),8.61(s,1H),8.43(s,1H),2.90(s,3H),1.37(s,9H).

[0520] Step 3: Preparation of (R)-2-methyl-N-((R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)propyl-2-sulfinamide [ka] To a mixture of (R,E)-2-methyl-N-(1-(3-nitro-5-(trifluoromethyl)phenyl)ethylidene)propyl-2-sulfinamide (10 g, 30.7 mmol) in THF (100 mL) and water (20 mL) was added NaBH (1.28 g, 33.7 mmol). The reaction mixture was stirred at −10° C. for 1 min. After that, the reaction mixture was quenched with water (300 mL) and the solution was extracted with EA (200 mL × 3). The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give the target product, (R)-2-methyl-N-((R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)propyl-2-sulfinamide. 1H NMR(400MHz,CDCl3) δ8.45-8.42(m,2H),7.96(s,1H),4.76-4.68(m,1H),3.56(d,J=4.2Hz,1H),1.62(d,J=6.7Hz,3H),1.26(s,9H).

[0521] Step 4: Preparation of (R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl-1-amine hydrochloride [ka] (R)-2-Methyl-N-((R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)propyl-2-sulfinamide (5.5 g, 16.3 mmol) was placed in a solution of hydrochloric acid (80 mL, 4 M) in dioxane and stirred at 25 °C for 2 h. The crude product was filtered and washed with petroleum ether (100 mL) to give the target product, (R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl-1-amine hydrochloride. LC-MS: (ESI, m / z): [M+H] + =235.2.

[0522] Intermediate 2: Ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylate

[0523] Step 1: Preparation of ethyl 4-(((trifluoromethyl)sulfonyl)oxy)cyclohexyl-3-ene-1-carboxylate [ka] To a stirred mixture of ethyl 4-oxocyclohexane-1-formate (5 g, 32.0 mmol) and 2,6-dimethylpyridine (4.6 g, 42.9 mmol) in DCM (60 mL) at 0 °C, TfO (9 g, 32.0 mmol) was added dropwise. The reaction mixture was stirred at 0 °C for 1 h. The reaction mixture was then stirred at 25 °C for 15 min, and TfO (7 g, 25.6 mmol) was added. The reaction mixture was stirred at 25 °C overnight. The reaction mixture was concentrated, quenched with water (300 mL), and extracted with EA (200 mL × 3). The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give ethyl 4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-ene-1-carboxylate. 1 H NMR(400MHz,DMSO-d6) δ5.90(d,J=3.9Hz,1H),4.14-4.02(m,2H),2.68-2.60(m,1H),2.47-2.27(m,4H),2.08-1.98(m,1H),1.88-1.76(m,1H),1.19(t,J=7.1Hz,3H).

[0524] Step 2: Preparation of ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexyl-3-ene-1-carboxylate [ka] A mixture of ethyl 4-(((trifluoromethyl)sulfonyl)oxy)cyclohex-3-ene-1-carboxylate (4.7 g, 16.8 mmol), (Bpin)2 (6.4 g, 25.2 mmol), Pd(dppf)2Cl2 (1.2 g, 1.68 mmol), and KOAc (4.9 g, 50.4 mmol) in 1,4-dioxane (80 mL) was stirred at 90 °C overnight. The reaction was quenched with water (300 mL) and extracted with EA (200 mL × 3). The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylate. 1 H NMR(400MHz,DMSO-d6) δ6.42(d,J=2.2Hz,1H),4.11-4.02(m,2H),2.33-1.95(m,4H),1.93-1.83(m,1H),1.53-1.38(m,1H),1.21-1.14(m,16H).

[0525] Intermediate 3: ((1R,4R)-4-(4-(((R)-1-(3-amino)-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexyl)(piperazin-1-yl)methanone

[0526] Step 1: Preparation of 2-amino-5-bromo-4-methoxybenzoic acid [ka] To a stirred solution of 2-amino-4-methoxybenzoic acid (30 g, 179 mmol) in DMF (600 mL) was added NBS (35 g, 197 mmol) at 0 °C, and the reaction mixture was stirred at 25 °C for 1 h. The reaction mixture was quenched with sodium thiosulfate (saturated aqueous solution, 500 mL) and extracted with EA (500 mL × 3). The organic layer was collected, washed with sodium chloride (saturated aqueous solution, 500 mL × 3), dried over anhydrous sodium sulfate, filtered, and concentrated to give crude 2-amino-5-bromo-4-methoxybenzoic acid, which was used directly in the next step without further purification. LC-MS: (ESI, m / z): [M+H] + =246.0.

[0527] Step 2: Preparation of 6-bromo-7-methoxy-2-methylquinazolin-4(3H)-one [ka] To a stirred solution of 2-amino-5-bromo-4-methoxybenzoic acid (17.0 g, 69.1 mmol) in methanol (170 mL) were added ammonium acetate (53.2 g, 691 mmol) and trimethyl orthoacetate (83.0 g, 691 mmol). The resulting reaction mixture was stirred in a sealed vessel at 120 °C for 24 h. The reaction mixture was poured into water (1 L) and the solid product was filtered. The crude product was washed with EA (1 L) to give the target product, 6-bromo-7-methoxy-2-methylquinazolin-4(3H)-one. The crude product was used directly in the next step without purification. LC-MS: (ESI, m / z): [M+H] + =268.9.

[0528] Step 3: Preparation of 6-bromo-4-chloro-7-methoxy-2-methylquinazoline [ka] A mixture of 6-bromo-7-methoxy-2-methylquinazolin-4(3H)-one (10 g, 37.2 mmol) in phosphorus oxychloride (200 mL) was stirred at 105° C. overnight. The reaction mixture was concentrated, quenched with sodium bicarbonate (saturated aqueous solution, 500 mL), and extracted with EA (300 mL × 3). The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by silica gel column chromatography to give the target product, 6-bromo-4-chloro-7-methoxy-2-methylquinazoline. LC-MS: (ESI, m / z): [M+H] + =287.0.

[0529] Step 4: Preparation of (R)-6-bromo-7-methoxy-2-methyl-N-(1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)quinazolin-4-amine [ka] To a mixture of 6-bromo-4-chloro-7-methoxy-2-methylquinazoline (1.8 g, 6.27 mmol) in EtOH (12 mL) was added (R)-1-(3-nitro-5-(trifluoromethyl))phenyl)ethyl-1-amine hydrochloride (1.7 g, 7.52 mmol) and DIEA (1.6 g, 12.5 mmol). The reaction mixture was stirred in a microwave at 100 °C for 5 h. The reaction was quenched with water (300 mL) and extracted with EA (300 mL × 3). The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give (R)-6-bromo-7-methoxy-2-methyl-N-(1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)quinazolin-4-amine as a yellow oil. LC-MS: (ESI, m / z): [M+H] + =484.9.

[0530] Step 5: Preparation of ethyl 4-(7-methoxy-2-methyl-4-(((R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)amino)quinazolin-6-yl)cyclohexyl-3-ene-1-carboxylate [ka] A reaction mixture of (R)-6-bromo-7-methoxy-2-methyl-N-(1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)quinazolin-4-amine (2 g, 4.12 mmol), ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylate (2.31 g, 8.24 mmol), sodium carbonate (873 mg, 8.24 mmol), and Pd(dppf)Cl (300 mg, 0.41 mmol) in DMF (24 mL) and water (3 mL) was stirred at 110 °C overnight. The reaction was quenched with water (300 mL). The solution was extracted with EA (300 mL × 3) and washed with sodium chloride (saturated aqueous solution, 500 mL × 3), and the organic layers were combined. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give ethyl 4-(7-methoxy-2-methyl-4-(((R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)amino)quinazolin-6-yl)cyclohex-3-ene-1-carboxylate. LC-MS: (ESI, m / z): [M+H] + =559.7.

[0531] Step 6: Preparation of ethyl (R)-4-(4-((1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexyl-1-carboxylate [ka] To a mixture of ethyl 4-(7-methoxy-2-methyl-4-(((R)-1-(3-nitro-5-(trifluoromethyl)phenyl)ethyl)amino)quinazolin-6-yl)cyclohex-3-ene-1-carboxylate (1.7 g, 3.04 mmol) in MeOH (60 mL) solution was added Pd / C (1.02 g, 0.6 w / w). The reaction mixture was stirred under a hydrogen atmosphere at 50° C. and reacted for 4 days. The crude product was filtered to give ethyl (R)-4-(4-((1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexa-1-carboxylate. LC-MS: (ESI, m / z): [M+H] + =531.2.

[0532] Step 7: Preparation of (1R,4R)-4-(4-(((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexane-1-formic acid [ka] To a mixture of ethyl (R)-4-(4-((1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexane-1-carboxylate (1.5 g, 2.82 mmol) in methanol (8 mL), THF (8 mL), and water (16 mL) was added lithium hydroxide (203 mg, 8.46 mmol). The reaction mixture was stirred at 60° C. and reacted overnight. The crude product was purified by preparative HPLC to give (1R,4R)-4-(4-(((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexane-1-formic acid. LC-MS: (ESI, m / z): [M+H] + =503.2. 1H NMR(400MHz,DMSO-d6) δ8.13(d,J=8.0Hz,1H),8.06(s,1H),6.99(s,1H),6.88(s,1H),6.86(s,1H),6.69(s,1H),5.56(dd,J=13.6,5.8Hz,3H),3.88(s,3H) ),2.92(t,J=11.7Hz,1H),2.35(s,3H),2.24(t,J=11.8Hz,1H),2.05(d,J=10.8Hz,2H),1.87(d,J=11.8Hz,2H),1.66-1.40(m,7H).

[0533] Step 8: tert-butyl 4-((1R,4R)-4-(4-(((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexane-1-carbonyl)piperazine-1-carboxylate [ka] To a mixture of (1R,4R)-4-(4-(((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexane-1-formic acid (220 mg, 0.44 mmol) in EA (12 mL) was added tert-butyl piperazine-1-formate (163 mg, 0.88 mmol), DIEA (169 mg, 1.31 mmol), and T3P (209 mg, 0.66 mmol). The reaction mixture was stirred at 0°C for 3 h. The reaction was quenched with water (100 mL) and extracted with EA (100 mL × 3). The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography to give tert-butyl 4-((1R,4R)-4-(4-(((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexane-1-carbonyl)piperazine-1-carboxylate. LC-MS: (ESI, m / z): [M+H] + =671.3. 1H NMR(400MHz,DMSO-d6) δ8.19-8.07(m,2H),6.99(s,1H),6.86(d,J=10.5Hz,2H),6.70(s,1H),5.56(dd,J=16.7,9.3Hz,3H),3.89(s,3H),3.47( m,4H),3.32(m,4H),2.95(s,1H),2.67(s,1H),2.36(s,3H),1.83(d,J=14.5Hz,4H),1.59(t,J=22.3Hz,7H),1.41(s,9H).

[0534] Step 9: Preparation of ((1R,4R)-4-(4-(((R)-1-(3-amino)-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexyl)(piperazin-1-yl)methanone [ka] A mixture of tert-butyl 4-((1R,4R)-4-(4-(((R)-1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexane-1-carbonyl)piperazine-1-carboxylate (220 mg, 0.33 mmol) in ethyl acetate / hydrochloric acid (3 M, 10 mL) was stirred at 25° C. and reacted for 2 h. The reaction was concentrated to give ((1R,4R)-4-(4-(((R)-1-(3-amino)-5-(trifluoromethyl)phenyl)ethyl)amino)-7-methoxy-2-methylquinazolin-6-yl)cyclohexyl)(piperazin-1-yl)methanone, which could be used crude in the next step without further purification. LC-MS: (ESI, m / z): [M+H] + =571.2.

[0535] Intermediate 4: 2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)acetaldehyde

[0536] Step 1: 2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione [ka] To a solution of 4-fluorophthalic acid (5.52 g, 0.03 mol) in acetic acid (50 mL), 3-aminopiperidine-2,6-dione hydrochloride (5.0 g, 0.03 mol) and potassium acetate (8.8 g, 0.09 mol) were added, and the reaction mixture was stirred at 120° C. overnight. The reaction mixture was concentrated under reduced pressure, and the concentrate was diluted with water (100 mL), stirred at room temperature for 30 minutes, filtered, and the solid was washed with water (50 mL × 2). The product was obtained by drying under reduced pressure. LC-MS: (ESI, m / z): [M+H] + =277.1

[0537] Step 2: Preparation of 2-(2,6-dioxopiperidin-3-yl)-5-(4-(2-hydroxyethyl)piperidin-1-yl)isoindoline-1,3-dione [ka] A mixture of 2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione (500 mg, 1.81 mmol), 2-(piperidin-4-yl)ethyl-1-ol (280 mg, 2.17 mmol), and DIEA (701 mg, 5.43 mmol) in NMP (5 mL) was reacted in a microwave reactor at 140 °C for 5 hours. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL × 2). The organic phase was collected, washed with water (100 mL × 2) and saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified using a silica gel column to obtain the product. LC-MS: (ESI, m / z): [M+H] + =386.1.

[0538] Step 3: Preparation of 2-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)acetaldehyde [ka] A mixture of 2-(2,6-dioxopiperidin-3-yl)-5-(4-(2-hydroxyethyl)piperidin-1-yl)isoindoline-1,3-dione (300 mg, 0.78 mmol) and IBX (436 mg, 1.56 mmol) in acetonitrile (6 mL) was stirred at 80 °C for 2 h. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (30 mL × 2). The organic phase was collected, washed with water (50 mL × 2) and saturated brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by silica gel column chromatography to give the product. LC-MS: (ESI, m / z): [M+H] + =384.1. 1H NMR(400MHz,DMSO-d6) δ11.07(s,1H),9.69(t,J=1.6Hz,1H),7.65(d,J=8.6Hz,1H),7.31(d,J=2. 0Hz,1H),7.23(dd,J=8.6,2.2Hz,1H),5.06(dd,J=12.9,5.4Hz,1H),4.03(d d,J=10.3,2.9Hz,2H),3.04-2.82(m,3H),2.65-2.52(m,2H),2.41(dd,J=6. 7,1.6Hz,2H),2.17-1.97(m,2H),1.73(d,J=11.1Hz,2H),1.2-1.18(m,2H).

[0539] Intermediate 5: 2-(3-(4-chloro-3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)benzoyl)-3-azaspiro[5.5]undecan-9-yl)acetaldehyde

[0540] Step 1: Preparation of 4-chloro-3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)benzoic acid [ka] 3-Amino-4-chlorobenzoic acid (5.0 g, 2.93 mmol) was suspended in acrylic acid (8.05 mL, 117 mmol) and stirred at 100 °C for 3 h. The reaction mixture was then stirred and cooled to room temperature. Acetic acid (33 mL) was added, and the stirred suspension was heated at 100 °C for 10 min. Urea (11.00 g, 183 mmol) was added, and the reaction mixture was stirred at 120 °C overnight. The reaction mixture was added to a mixture of ice water and concentrated hydrochloric acid (37%) and stirred. The resulting suspension was stored in a refrigerator at 5 °C overnight. The mixture was then filtered, washed with water, and dried to give the target product. The solid was triturated with hydrochloric acid solution (0.05 M), filtered, washed with methyl tert-butyl ether, and dried under reduced pressure at 40 °C to give the target product. LC-MS: (ESI, m / z): [M+H] + =269.0

[0541] Step 2: Preparation of pentafluorophenyl 4-chloro-3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)benzoate [ka] A mixture of 4-chloro-3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)benzoic acid (2.0 g, 7.58 mmol), 2,3,4,5,6-pentafluorophenol (1.67 g, 9.09 mmol), and N,N'-dicyclohexylcarboimide (1.87 g, 9.09 mmol) in N,N-dimethylformamide (20 mL) was stirred at room temperature for 3 h. The reaction mixture was poured into water (200 mL) and stirred for 0.5 h. The solution was extracted with ethyl acetate (200 mL × 3). The organic phase was collected, washed with water (500 mL × 2) and saturated brine (300 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by silica gel column chromatography to give the target product. LC-MS: (ESI, m / z): [M+H] + =435.0

[0542] Step 3: Preparation of 2-(3-aza[5.5]undecan-9-yl)ethan-1-ol [ka] To a mixture of benzyl 9-(2-hydroxyethyl)-3-azaspiro[5.5]undecane-3-carboxylate (1.0 g, 3 mmol) in EA (10 mL) was added Pd(OH) / C (200 mg), and the reaction mixture was stirred at room temperature under a hydrogen atmosphere for 16 h. The mixture w...

Claims

1. A compound of formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof, S-L-E I Where: S is a small molecule compound capable of inhibiting SOS1 protein activity or binding to SOS1 protein; L is a linking chain connecting S and E via a covalent bond; E is a small molecule ligand of the E3 ubiquitin ligase complex; A compound of Formula I, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

2. S is S1, S1', -X-S1', S1'', -X-S1'', S2, S2', -X-S2', S2'', -X-S2'', S3, S4, S5, S5' or -X-S2'', and X is O, NH or S, preferably O; 【Chemistry 1】 Here, in S1, S1', and S1'', R １ is hydrogen, halogen, -OH, -CN, -NO ２ , C １ -C ６ Alkylmercapto group or -NR ａ R ｂ wherein R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R １ is C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkoxy group, C ３ -C ６ Heterocycloalkoxy group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C ４ -C ８ Cycloalkenyl groups, 4- to 7-membered heterocycloalkyl groups, 5- to 10-membered heterocycloalkenyl groups, spiroheterocycloalkyl groups, fused heterocycloalkyl groups, bridged heterocycloalkyl groups, phenyl groups, heteroaryl groups, C １ -C ６ Haloalkyl groups, -COOH, -COOR ｃ wherein R ｃ is -C １ -C ６ Alkyl group, C ３ -C ６ Alkenyl group, C ３ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group or -C ４ -C ８ is a cycloalkenyl group, R １ is -NS(O)(R ｄ ) (R ｅ ) wherein C １ -C ６ and R ｅ are each independently C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C ４ -C ８ a cycloalkenyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group; R １ is -NHC(O)-(C １ -C ６ alkyl), -NHC(O)-NR ａ R ｂ and R ａ and R ｂ each independently represents hydrogen, -C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R １ is -NH-(CH ２ ) ｋ -NH-C(O)-R ａａ and R ａａ is C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group and k is 1 or 2; R １ is -NH-(CH ２ ) ｉ -R ｆ wherein i is 0, 1 or 2, and R ｆ represents a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, C １ -C ６ is an alkylsulfonyl group, In addition, the C １ -C ６ Alkyl group, C １ -C ６ The alkoxy, 4- to 7-membered heterocycloalkyl and heteroaryl groups are optionally substituted with halogen, —OH, oxo, —CN, —NO ２ , C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl groups, 4- to 7-membered heterocycloalkyl groups, C １ -C ６ Alkoxy group, C １ -C ６ Haloalkyl group, C １ -C ６ Haloalkoxy group, C １ -C ６ Alkyl sulfonyl group, phenyl group, benzyl group, heteroaryl group, -(CH ２ )-heteroaryl group, —NHC(O)(C １ -C ６ Alkyl), C ３ -C ８ A cycloalkoxy group, a phenoxy group, a heteroaryloxy group, or -NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ cycloalkyl groups, R １ is -O-(CH ２ ) ｚ -phenyl group, -O-(CH ２ ) ｚ -(4- to 7-membered heterocycloalkyl), -O-(CH ２ ) ｚ -heteroaryl group, z is 0, 1 or 2, and the phenyl group, heterocycloalkyl group and heteroaryl group are optionally substituted with a group selected from -OH, a heterocycloalkyl group or a heterocycloalkenyl group, and can be substituted with a methyl group or an oxo group; Or R １ teeth, 【Chemistry 2】 and Or two adjacent R １ together with the carbon atom to which each is attached form a 5- to 7-membered cycloalkyl group or a 5- to 7-membered heterocycloalkyl group; and x is 1, 2 or 3; A １ is C ４ -C １２ a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; R ２ is hydrogen, -OH, oxo, halogen, -CN, C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ２ -C ６ Alkenyl group, -C ２ -C ６ Alkynyl group, -C ３ -C ８ Cycloalkyl group, -C ３ -C ８ Cycloalkoxy group, -C ３ -C ８ halocycloalkoxy group, -C ４ -C ８ Cycloalkenyl group, 4- to 7-membered heterocycloalkyl group, -O-CH ２ -4 to 7 membered heterocycloalkyl group, 5 to 10 membered heterocycloalkenyl group, spiroheterocycloalkyl group, fused heterocycloalkyl group, bridged heterocycloalkyl group, phenyl group, heteroaryl group, -C １ -C ６ Haloalkyl group, -C １ -C ６ haloalkoxy group, -C １ -C ６ is an alkylsulfonyl group, R ２ is -NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group or -C(O)C １ -C ３ is an alkyl group, R ２ is -C(O)NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ２ is -C(O)OR ｇ and R ｇ is hydrogen or C １ -C ６ is an alkyl group, R ２ is -OR ｈ and R ｈ is C １ -C ６ is an alkyl group, R ２ is -(CH ２ ) N.R. ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, and w is 1, 2, 3 or 4; The above A ２ (R ３ ) Ｙ is hydrogen, Or, A ２ is C ４ -C １２ a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, and R ３ is hydrogen, halogen, -OH, oxo, -CN, -NO ２ , C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C ４ -C ８ Cycloalkenyl group, C ７ -C ８ Cycloalkynyl group, 4- to 7-membered heterocycloalkyl group, 5- to 10-membered heterocycloalkenyl group, phenyl group, heteroaryl group, C １ -C ６ is a haloalkyl group, The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups may optionally be selected from the group consisting of halogen, -OH, oxo, -CN, -C １ -C ６ Alkyl group, -C １ -C ６ Alkoxy group, -C １ -C ６ A haloalkyl group, a phenyl group, a heteroaryl group, or a -C(O)NR ｉ R ｊ and R ｉ and R ｊ are each independently hydrogen or C １ -C ６ is an alkyl group, or the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups are optionally -NR ｋ R ｌ and R ｋ and R ｌ are each independently hydrogen, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C １ -C ６ Alkyl sulfonyl group, phenyl group, heteroaryl group, -CH ２ -C(O)-R ｍ , -C(O)R ｐ or a 4- to 7-membered heterocycloalkyl group, and the alkyl group, alkynyl group, alkenyl group, cycloalkyl group, phenyl group, heteroaryl group, and heterocycloalkyl group are each independently optionally selected from C １ -C ６ Haloalkyl group, -OH, oxo group, phenyl group, -CN, C １ -C ６ alkoxy or heteroaryl, and the heteroaryl is optionally substituted with a methyl group; and R ｍ is a bicyclic heteroaryl group, C １ -C ６ Alkoxy group or -NR ｎ R ｏ and R ｎ and R ｏ are each independently hydrogen, C １ -C ６ an alkyl group or a phenyl group, the alkyl group being optionally １ -C ６ substituted with an alkoxy group or a phenyl group, or -NR ｎ R ｏ is a 4- to 7-membered azacycloalkyl group, said azacycloalkyl group being linked to the rest of the molecule through an N atom and further comprising one or more heteroatoms selected from N or O; ｐ is C １ -C ６ an alkoxy group, optionally -OH or C １ -C ６ C substituted with 1, 2 or 3 groups selected from alkoxy groups １ -C ６ alkyl group, monocyclic or bicyclic heteroaryl group, 4- to 7-membered heterocycloalkyl group, or R ｐ is -CH ２ -NR ｑ R ｒ and R ｑ and R ｒ are each independently hydrogen, a phenyl group, or C optionally substituted with F. １ -C ６ selected from alkyl groups, or the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups are optionally -NR ｓ R ｔ and the -NR ｓ R ｔ is a 4- to 7-membered azacycloalkyl group linked to another part of the molecule through a nitrogen atom or a 6- to 10-membered azaspiroheterocycloalkyl group linked to another part of the molecule through a nitrogen atom, and further containing at most two heteroatoms selected from N or O, and optionally containing -OH, an oxo group, C １ -C ６ Alkyl group, C １ -C ６ Hydroxyalkyl group, -C(O)OR ｚ and R ｚ is C １ -C ６ Alkyl group, halogen, -N(C １ -C ６ Alkyl) ２ , -CH ２ N (C １ -C ６ Alkyl) ２ , -C(O)NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, Or R ３ is C(O)R ｖ , -C(O)NH ２ , -C(O)NHR ｖ , -C(O)NR ｖ R ｗ , -C(O)OR ｖ and R ｖ and R ｗ are each independently hydrogen, C １ -C ４ Alkyl group, C １ -C ４ A haloalkyl group, a phenyl group, or a -(CH ２ ) ２ N.R. ｘ R ｙ and R ｘ and R ｙ are each independently hydrogen, C １ -C ４ Alkyl group or -(CH ２ ) ２ N (CH ３ ) ２ and Or R ３ is -NH ２ , -NHR ｚ , -NR ｚ R ｚａ , -NHC(O)R ｚ , -NHC(O)OR ｚ , -NHS(O) ２ R ｚ , a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, a spiroheterocycloalkyl group, a fused heterocycloalkyl group, or a bridged heterocycloalkyl group, ｚ and R ｚａ are each independently C １ -C ４ Alkyl group, C １ -C ４ a haloalkyl group or a phenyl group, Or R ３ is C １ -C ６ Alkoxy group, C １ -C ６ Haloalkoxy groups, —O(CH ２ ) ｓ -C ３ -C ８ Cycloalkyl groups, -O(CH ２ ) ｓ -phenyl group, -O(CH ２ ) ｓ -heterocycloalkyl group, -O(CH ２ ) ｓ -heteroaryl group, where s is 0, 1, 2 or 3; Or R ３ is -S(O) ２ R ｚ , -S(O) ２ N.H. ２ , -S(O) ２ NHR ｚ , -S(O) ２ N.R. ｚ R ｚａ and R ｚ and R ｚａ are each independently C １ -C ４ Alkyl group, C １ -C ４ a haloalkyl group or a phenyl group, and y is 0, 1, 2, or 3; Y is 0, 1, 2, 3, 4 or 5; L' is a bond, -(CH ２ ) ｋ -, -O(CH ２ ) ｋ -, -(CH ２ ) ｋ -O- or -O-(CH ２ ) ｋ -O-, k is 0, 1, 2 or 3, or L' is -CH=CH-(CH ２ ) ｎ -, wherein n is 0, 1 or 2; R ４ , R ５ are each independently C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group or C ３ -C ６ and a cycloalkoxy group, wherein the alkyl group, the alkoxy group, the cycloalkyl group and the cycloalkoxy group are optionally selected from the group consisting of a cyano group, a hydroxy group, a C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group, C ３ -C ６ substituted with cycloalkoxy groups or halogens; 【Chemistry 3】 Here, in S2, S2', and S2'', R １ is hydrogen, halogen, -OH, -CN, -NO ２ , C １ -C ６ Alkylmercapto group or -NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R １ is C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkoxy group, C ３ -C ６ Heterocycloalkoxy group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C ４ -C ８ Cycloalkenyl groups, 4- to 7-membered heterocycloalkyl groups, 5- to 10-membered heterocycloalkenyl groups, spiroheterocycloalkyl groups, fused heterocycloalkyl groups, bridged heterocycloalkyl groups, phenyl groups, heteroaryl groups, C １ -C ６ Haloalkyl groups, -COOH, -COOR ｃ wherein R ｃ is -C １ -C ６ Alkyl group, C ３ -C ６ Alkenyl group, C ３ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group or -C ４ -C ８ is a cycloalkenyl group, R １ is -NS(O)(R ｄ ) (R ｅ ) wherein R ｄ and R ｅ are each independently C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C ４ -C ８ is a cycloalkenyl group, R １ is -NHC(O)-(C １ -C ６ alkyl), -NHC(O)-NR ａ R ｂ and R ａ and R ｂ each independently represents hydrogen, -C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R １ is -NH-(CH ２ ) ｋ -NH-C(O)-(C １ -C ６ alkyl), wherein k is 1 or 2; R １ is -NH-(CH ２ ) ｉ -R ｆ wherein i is 0, 1 or 2, and R ｆ represents a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, C １ -C ６ is an alkylsulfonyl group, In addition, the C １ -C ６ Alkyl group, C １ -C ６ The alkoxy, 4- to 7-membered heterocycloalkyl and heteroaryl groups are optionally substituted with halogen, —OH, oxo, —CN, —NO ２ , C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl groups, 4- to 7-membered heterocycloalkyl groups, C １ -C ６ Alkoxy group, C １ -C ６ Haloalkyl group, C １ -C ６ Haloalkoxy group, C １ -C ６ Alkyl sulfonyl group, phenyl group, benzyl group, heteroaryl group, -(CH ２ )-heteroaryl group, —NHC(O)(C １ -C ６ Alkyl), C ３ -C ８ A cycloalkoxy group, a phenoxy group, a heteroaryloxy group, or -NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ cycloalkyl groups, R １ is -O-(CH ２ ) ｚ -phenyl group, -O-(CH ２ ) ｚ -(4- to 7-membered heterocycloalkyl), -O-(CH ２ ) ｚ -heteroaryl group, z is 0, 1 or 2, and the phenyl group, heterocycloalkyl group and heteroaryl group are optionally substituted with a group selected from -OH, a heterocycloalkyl group or a heterocycloalkenyl group, and can be substituted with a methyl group or an oxo group; Or R １ teeth, 【Chemistry 4】 and the L ２ a is C(O), L ２ b is a bond or C １ -C ６ is an alkylene group, ２ teeth, 【Chemistry 5】 and Rx ２ teeth, 【Chemistry 6】 and Or R １ teeth, 【Chemistry 7】 and Or two adjacent R １ together with the carbon atom to which each is attached form a 5- to 7-membered cycloalkyl group or a 5- to 7-membered heterocycloalkyl group; and x is 1, 2, 3 or 4; A １ is C ４ -C １２ a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; R ２ is hydrogen, -OH, oxo, halogen, -CN, C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ２ -C ６ Alkenyl group, -C ２ -C ６ Alkynyl group, -C ３ -C ８ Cycloalkyl group, -C ３ -C ８ Cycloalkoxy group, -C ３ -C ８ halocycloalkoxy group, -C ４ -C ８ Cycloalkenyl group, 4- to 7-membered heterocycloalkyl group, -O-CH ２ -4 to 7 membered heterocycloalkyl group, 5 to 10 membered heterocycloalkenyl group, spiroheterocycloalkyl group, fused heterocycloalkyl group, bridged heterocycloalkyl group, phenyl group, heteroaryl group, -C １ -C ６ Haloalkyl group, -C １ -C ６ haloalkoxy group, -C １ -C ６ is an alkylsulfonyl group, R ２ is -NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ２ is -C(O)NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ２ is -C(O)OR ｇ and R ｇ is hydrogen or C １ -C ６ is an alkyl group, R ２ is -OR ｈ and R ｈ is C １ -C ６ is an alkyl group, R ２ is -(CH ２ ) N.R. ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, and w is 1, 2, 3 or 4; The above A ２ (R ３ ) Ｙ is hydrogen, Or, A ２ is C ４ -C １２ a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, and R ３ is hydrogen, halogen, -OH, oxo, -CN, -NO ２ , C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C ４ -C ８ Cycloalkenyl group, C ２ -C ８ Cycloalkynyl group, 4- to 7-membered heterocycloalkyl group, 5- to 10-membered heterocycloalkenyl group, phenyl group, heteroaryl group, C １ -C ６ is a haloalkyl group, The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups may optionally be selected from the group consisting of halogen, -OH, oxo, -CN, -C １ -C ６ Alkyl group, -C １ -C ６ Alkoxy group, -C １ -C ６ A haloalkyl group, a phenyl group, a heteroaryl group, or a -C(O)NR ｉ R ｊ and R ｉ and R ｊ are each independently hydrogen or C １ -C ６ is an alkyl group, or the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups are optionally -NR ｋ R ｌ and R ｋ and R ｌ are each independently hydrogen, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C １ -C ６ Alkyl sulfonyl group, phenyl group, heteroaryl group, -CH ２ -C(O)-R ｍ , -C(O)R ｐ or a 4- to 7-membered heterocycloalkyl group, and the alkyl group, alkynyl group, alkenyl group, cycloalkyl group, phenyl group, heteroaryl group, and heterocycloalkyl group are each independently optionally selected from the group consisting of C １ -C ６ Haloalkyl group, -OH, oxo group, phenyl group, -CN, C １ -C ６ alkoxy or heteroaryl, and the heteroaryl is optionally substituted with a methyl group; and R ｍ is a bicyclic heteroaryl group, C １ -C ６ Alkoxy group or -NR ｎ R ｏ and R ｎ and R ｏ are each independently hydrogen, C １ -C ６ an alkyl group or a phenyl group, the alkyl group being optionally １ -C ６ substituted with an alkoxy group or a phenyl group, or -NR ｎ R ｏ is a 4- to 7-membered azacycloalkyl group, said azacycloalkyl group being linked to the rest of the molecule through an N atom and further comprising one or more heteroatoms selected from N or O; ｐ is C １ -C ６ an alkoxy group, optionally -OH or C １ -C ６ C substituted with 1, 2 or 3 groups selected from alkoxy groups １ -C ６ alkyl group, monocyclic or bicyclic heteroaryl group, 4- to 7-membered heterocycloalkyl group, or R ｐ is -CH ２ -NR ｑ R ｒ and R ｑ and R ｒ are each independently hydrogen, a phenyl group, or C optionally substituted with F. １ -C ６ selected from alkyl groups, or the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkenyl, cycloalkynyl and heterocycloalkenyl groups are optionally -NR ｓ R ｔ and the -NR ｓ R ｔ is a 4- to 7-membered azacycloalkyl group linked to another part of the molecule through a nitrogen atom or a 6- to 10-membered azaspiroheterocycloalkyl group linked to another part of the molecule through a nitrogen atom, and further containing at most two heteroatoms selected from N or O, and optionally containing -OH, an oxo group, C １ -C ６ Alkyl group, C １ -C ６ Hydroxyalkyl group, -C(O)OR ｚ and R ｚ is C １ -C ６ Alkyl group, halogen, -N(C １ -C ６ Alkyl) ２ , -CH ２ N (C １ -C ６ Alkyl) ２ , -C(O)NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, Or R ３ is C(O)R ｖ , -C(O)NH ２ , -C(O)NHR ｖ , -C(O)NR ｖ R ｗ , -C(O)OR ｖ and R ｖ and R ｗ are each independently hydrogen, C １ -C ４ Alkyl group, C １ -C ４ A haloalkyl group, a phenyl group, or a -(CH ２ ) ２ N.R. ｘ R ｙ and R ｘ and R ｙ are each independently hydrogen, C １ -C ４ Alkyl group or -(CH ２ ) ２ NH (CH ３ ) ２ and Or R ３ is -NH ２ , -NHR ｚ , -NR ｚ R ｚａ , -NHC(O)R ｚ , -NHC(O)OR ｚ , -NHS(O) ２ R ｚ , a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, a spiroheterocycloalkyl group, a fused heterocycloalkyl group, or a bridged heterocycloalkyl group, ｚ and R ｚａ are each independently C １ -C ４ Alkyl group, C １ -C ４ a haloalkyl group or a phenyl group, Or R ３ is C １ -C ６ Alkoxy group, C １ -C ６ Haloalkoxy groups, —O(CH ２ ) ｓ -C ３ -C ８ Cycloalkyl groups, -O(CH ２ ) ｓ -phenyl group, -O(CH ２ ) ｓ -heterocycloalkyl group, -O(CH ２ ) ｓ -heteroaryl group, where s is 0, 1, 2 or 3; Or R ３ is -S(O) ２ R ｚ , -S(O) ２ N.H. ２ , -S(O) ２ NHR ｚ , -S(O) ２ N.R. ｚ R ｚａ and R ｚ and R ｚａ are each independently C １ -C ４ Alkyl group, C １ -C ４ a haloalkyl group or a phenyl group, Y is 0, 1, 2, 3, 4 or 5; L' is a bond, -(CH ２ ) ｋ -, -O(CH ２ ) ｋ -, -(CH ２ ) ｋ -O- or -O-(CH ２ ) ｋ -O-, k is 0, 1, 2 or 3, or L' is -CH=CH-(CH ２ ) ｎ -, wherein n is 0, 1 or 2; R ４ , R ５ are each independently C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group or C ３ -C ６ and a cycloalkoxy group, wherein the alkyl group, the alkoxy group, the cycloalkyl group and the cycloalkoxy group are optionally selected from the group consisting of a cyano group, a hydroxy group, a C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group, C ３ -C ６ substituted with cycloalkoxy groups or halogens; T and V are both N, or T is C and V is N, or T is N and V is C; 【Chemistry 8】 Here, in S3, Q １ and Q. ２ are each independently CH or N; Q ３ , Q ４ and Q. ７ are each independently C or N, ３ and Q. ４ At least one of Q is C; ３ , Q ４ and Q. ７ is not all N, Q ５ is CH, N, NH, O or S, Q ６ is CH, N, NH, N(C １ -C ６ Alkyl), N(C １ -C ６ N(3- to 7-membered heteroalkyl), N(3- to 7-membered cycloalkyl), N(3- to 7-membered heterocycle), O or S; Q １ , Q ２ , Q ３ , Q ４ , Q ５ , Q ６ and Q. ７ at least one of is N, NH, O or S; R １ is hydrogen, C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, halogen, -NHR １ａ , -OR １ａ , C ３ -C ６ Cycloalkyl group, C ３ -C ６ A cycloalkoxy group or -CN, １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group and C ３ -C ６ The cycloalkoxy group is optionally substituted with halogen, -NHR １ａ Or -OR １ａ and R １ａ is hydrogen, C １ -C ６ Alkyl group, 3- to 6-membered heterocycle or C １ -C ６ is a haloalkyl group, L ２ represents a bond, -C(O)-, -C(O)O-, -C(O)NH(CH ２ ) ｏ -, -S(O) ２ -, -S(O)-, -S(=O)(=NH)-, -S(=O)[=N(C １ -C ６ alkyl)]-, -N(C １ -C ６ alkyl)-, -C(O)(CH ２ ) ｐ -, -(CH ２ ) ｐ - or O, wherein o is 0, 1 or 2, and p is an integer from 1 to 6; R ２ is hydrogen, halogen, -CN, -NO ２ , C １ -C ６ Alkylmercapto group, C ２ -C ６ Alkynyl group, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, -NR ２ｂ R ２ｃ , -OR ２ａ , a 3- to 14-membered cycloalkyl group, a 3- to 14-membered cycloalkenyl group, a 3- to 14-membered heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; １ -C ６ Alkyl group, C ２ -C ６ The alkenyl group, the 3- to 14-membered cycloalkyl group, the 3- to 14-membered cycloalkenyl group, the 3- to 14-membered heterocycloalkyl group, the 6- to 10-membered aryl group and the 5- to 10-membered heteroaryl group are each independently optionally selected from the group consisting of C １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, -OH, -OR ２ａ , oxo group, halogen, -C(O)R ２ａ , -C(O)OR ２ａ , -C(O)NR ２ｂ R ２ｃ , -CN, -NR ２ｂ R ２ｃ , a 3- to 6-membered cycloalkyl group, a 3- to 7-membered heterocycloalkyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group; ２ａ is hydrogen, C １ -C ６ Alkyl group, C １ -C ６ A haloalkyl group, a 3- to 7-membered heterocycloalkyl group, or -(CH ２ ) ｒ OCH ３ wherein r is 1, 2 or 3; The R ２ｂ is hydrogen or C １ -C ６ is an alkyl group, The R ２ｃ is hydrogen or C １ -C ６ is an alkyl group, R ２ is -NHC(O)-(C １ -C ６ alkyl), -NHC(O)-NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ２ is -NH-(CH ２ ) ｋ -NH-C(O)-(C １ -C ６ alkyl), wherein k is 1 or 2; R ２ is -NH-(CH ２ ) ｉ -R ｆ wherein i is 0, 1 or 2, and R ｆ represents a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, C １ -C ６ is an alkylsulfonyl group, R ３ and R ４ are each independently hydrogen, C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group or C ３ -C ６ is a cycloalkoxy group, and said R ３ and R ４ At least one of R ３ and R ４ together with the atoms to which they are connected form a 3- to 6-membered cycloalkyl group, and the alkyl, alkoxy, cycloalkyl and cycloalkoxy groups are optionally substituted with cyano, hydroxy, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group, C ３ -C ６ substituted with cycloalkoxy groups or halogens; A is an optionally substituted 6-membered aryl group or an optionally substituted 5- to 6-membered heteroaryl group; 【Chemistry 9】 Here, in S4, Q １ is CH or N, Q ４ is CH, C or N, Each Q ２ are each independently C-R １ or N, and Q ２ One of them is N and the other is Q. ２ is C-R １ and Each Q ３ and Q. ５ The molecules are independently C(R ＱＣ ) ２ , N.R. ＱＮ , C(O), O, S or SO ２ and R ＱＣ are each independently hydrogen, F, Cl, Br, or a 6- to 10-membered aryl group, ＱＮ are each independently hydrogen, C １ -C ６ an alkyl group or a 6- to 10-membered aryl group; Q １ , Q ２ , Q ３ , Q ４ and Q. ５ At least one of is N, NR ＱＮ , O or SO ２ and m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; and when m is 0, n is not 0; R １ is hydrogen, C １ -C ６ Alkyl group, halogen, -C(O)NHR １ａ , -NHR １ａ , -OR １ａ , a cyclopropyl group, azetidine or -CN, １ -C ６ The alkyl group and the azetidine are optionally substituted with halogen, R １ａ , -NHR １ａ Or -OR １ａ and R １ａ is hydrogen, C １ -C ６ Alkyl group, cyclopropyl group, 3- to 6-membered heterocycle or C １ -C ６ is a haloalkyl group, L ２ represents a bond, -C(O)-, -C(O)O-, -C(O)NH(CH ２ ) ｏ -, -S(O) ２ -, -S(O)-, -S(=O)(=NH)-, -S(=O)[=N(C １ -C ６ alkyl)]-, -N(C １ -C ６ alkyl)-, -C(O)(CH ２ ) ｐ -, -(CH ２ ) ｐ - or O, wherein o is 0, 1 or 2, and p is an integer from 1 to 6; R ２ is hydrogen, C １ -C ６ Alkyl group, -NR ２ｂ R ２ｃ , -OR ２ａ , a 3- to 14-membered cycloalkyl group, a 3- to 14-membered cycloalkenyl group, a 3- to 14-membered heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group; １ -C ６ The alkyl group, the 3- to 14-membered cycloalkyl group, the 3- to 14-membered cycloalkenyl group, the 3- to 14-membered heterocycloalkyl group, the 6- to 10-membered aryl group and the 5- to 10-membered heteroaryl group are each independently optionally selected from the group consisting of C １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C １ -C ６ Hydroxyalkyl group, C １ -C ６ Methoxyalkyl group, -OH, -OR ２ａ , oxo group, halogen, ═N, —C(O)R ２ａ , -C(O)OR ２ａ , -C(O)NR ２ｂ R ２ｃ , -S(O) ２ R ２ａ , -CN, -NR ２ｂ R ２ｃ , a 3- to 6-membered cycloalkyl group, a 3- to 7-membered heterocycloalkyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group; ２ａ is hydrogen, C １ -C ６ Alkyl group, C １ -C ６ A haloalkyl group, a 3- to 7-membered heterocycloalkyl group, or -(CH ２ ) ｒ OCH ３ wherein r is 1, 2 or 3; The R ２ｂ is hydrogen or C １ -C ６ is an alkyl group, The R ２ｃ is hydrogen or C １ -C ６ is an alkyl group, R ３ and R ４ each independently represents hydrogen, optionally substituted with halogen, —OH １ -C ６ is an alkyl group, ３ and R ４ At least one of R ３ and R ４ together with the atoms to which they are attached form a 3- to 6-membered cycloalkyl group; A is an optionally substituted 6-membered aryl group or an optionally substituted 5- to 6-membered heteroaryl group; As a condition, 【Chemistry 10】 but 【Chemistry 11】 If R １ is not hydrogen, 【Chemistry 12】 Here, in S5 and S5', The R １ is hydrogen or R ａ１ and R ａ１ is C １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C ２ -C ６ Alkenyl group, C １ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ４ -C １０ Cycloalkenyl group, 3- to 10-membered heterocycloalkyl group, C ６ -C １０ An aryl group or a 5- to 10-membered heteroaryl group, １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C ２ -C ６ Alkenyl group, C １ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ４ -C １０ Cycloalkenyl group, 3- to 10-membered heterocycloalkyl group, C ６ -C １０ The aryl group and the 5- to 10-membered heteroaryl group may optionally be one or more identical or different R ｂ１ and / or R ｃ１ is replaced by Each R ｂ１ each independently represents -OR ｃ１ , -NR ｃ１ R ｃ１ , halogen, -CN, -C(O)R ｃ１ , -C(O)OR ｃ１ , -C(O)NR ｃ１ R ｃ１ , -S(O) ２ R ｃ１ , -S(O) ２ N.R. ｃ１ R ｃ１ , -NHC(O)R ｃ１ , -N(C １ -C ４ alkyl)C(O)R ｃ１ , -NHC(O)OR ｃ１ Or -N(C １ -C ４ alkyl)C(O)OR ｃ１ and Each R ｃ１ are each independently hydrogen, C １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ４ -C １０ Cycloalkenyl group, 3- to 10-membered heterocycloalkyl group, C ６ -C １０ An aryl group or a 5- to 10-membered heteroaryl group, １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ４ -C １０ Cycloalkenyl group, 3- to 10-membered heterocycloalkyl group, C ６ -C １０ The aryl group and the 5- to 10-membered heteroaryl group each independently optionally have one or more identical or different R ｄ１ and / or R ｅ１ is replaced by Each R ｄ１ each independently represents -OR ｅ１ , -NR ｅ１ R ｅ１ , halogen, -CN, -C(O)R ｅ１ , -C(O)OR ｅ１ , -C(O)NR ｅ１ R ｅ１ , -S(O) ２ R ｅ１ , -S(O) ２ N.R. ｅ１ R ｅ１ , -NHC(O)R ｅ１ , -N(C １ -C ４ alkyl)C(O)R ｅ１ , -NHC(O)OR ｅ１ Or -N(C １ -C ４ alkyl)C(O)OR ｅ１ and Each R ｅ１ are each independently hydrogen, C １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ４ -C １０ Cycloalkenyl group, 3- to 10-membered heterocycloalkyl group, C ６ -C １０ an aryl group or a 5- to 10-membered heteroaryl group; R ２ is hydrogen, C １ -C ４ Alkyl group, C ３ -C ６ selected from a cycloalkyl group, a 3- to 6-membered heterocycloalkyl group, or a halogen; Ring A is C ６ -C １０ an aryl group, a 5- to 10-membered heteroaryl group, or a 9- to 10-membered bisheterocycloalkyl group; p is 1, 2 or 3; Each R ４ are each independently a hydrogen atom, a hydroxyl group, an oxo group, a halogen atom, a cyano group, １ -C ４ Alkyl group, -NH ２ , C １ -C ４ Haloalkyl group, C ２ -C ４ Alkenyl group, C ２ -C ４ Alkynyl group, C １ -C ４ Hydroxyalkyl group, hydroxy-C １ -C ４ Haloalkyl group, C ３ -C ６ Cycloalkyl group, C ３ -C ６ Cycloalkoxy group, 3- to 6-membered heterocycloalkyl group, C ３ -C ６ Hydroxycycloalkyl group, 3- to 6-membered heterocycloalkyl group substituted C １ -C ４ Haloalkyl groups, hydroxy groups, halogens, -NH ２ , -S(O) ２ - (C １ -C ４ a 3- to 6-membered heterocycloalkyl group substituted with an alkyl group or an oxo group, and the oxo group is substituted only on the non-aromatic ring; R ４ is -NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ４ is -C(O)NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ４ is -C(O)OR ｇ and R ｇ is hydrogen or C １ -C ６ is an alkyl group, R ４ is -OR ｈ and R ｈ is C １ -C ６ is an alkyl group, Or, R ４ is -(CH ２ ) N.R. ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ３ and R ５ are each independently hydrogen, C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group or C ３ -C ６ and a cycloalkoxy group, wherein the alkyl group, the alkoxy group, the cycloalkyl group and the cycloalkoxy group are optionally selected from the group consisting of a cyano group, a hydroxy group, a C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group, C ３ -C ６ substituted with cycloalkoxy groups or halogens; 10. A compound of formula I according to claim 1, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

3. S is S1a, S1a', -X-S1a', S1a'', -X-S1a'', S2a, S2a', -X-S2a', S2a'', -X-S2a'', S3a, S4a, S5a, S5a' or -X-S5a'; X is O, NH or S, preferably O; 【Chemistry 13】 In the above S1a, S1a', and S1a'', R １ is hydrogen, -OCH ３ -, -OCH ２ CH ３ , 【Chemistry 14】 、-CH ２ O, -C (O) O, -C (O) O ３ ,-B2,-OCH(CH ３）２ ,-O(CH ２ ) ２ HH(H) ３ ) ２ ,-O(CH ２ ) ３ CH ３ ,-O(CH ２ ) ２ OCH ３ 、 【Chemistry 15】 , -O(CH ２ )-phenyl group, -N=S(O)(CH ３ ) ２ , -CH ３ , cyclopropyl group, -N(CH ３ ) ２ , -NHCH ３ , -NH ２ , 【Chemistry 16】 、-C(CH ３ ) ２ -OH、 【Chemistry 17】 , -NH(CH ２ )-NH-C(O)CH ３ , -NH(CH ２ )-morpholine, —NH—C(O)CH ３ , -NH-C(O)NHCH ３ , -NH-C(O)-N(CH ３ ) ２ , nitro group, —NH—S(O) ２ CH ３ , -N=S(O)(CH ３ ) ２ , a hydroxy group, —O—(CH ２ ) ２ -S (O) ２ CH ３ , -F, 【Chemistry 18】 , a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexa group, an azetidinyl group, an azacyclopentyl group, a piperidinyl group, a piperazinyl group, an oxetane group, an oxolane group, an oxane group, a thietane group, a thiolane group, a thiane group, an azacyclobutanyloxy group, an azacyclopentyloxy group, a piperidinyloxy group, a piperazinyloxy group, an oxetanyloxy group, an oxolanyloxy group, an oxanyloxy group, a thietanyloxy group, a thianyloxy group, a thiolanyloxy group, 【Chemistry 19】 ,-OCH ２ CH ２ CH ３ ,-OCH ２ CH ２ CH ２ N(CH) ３ ) ２ ,-OCH ２ CH ２ CH ２ Oh, 【Chemistry 20】 ,-OCH ２ CH ２ NC(O)CH ３ ,-OCH ２ CH ２ N(CH) ３ ) ２ ,-OCH ２ CH ２ Oh, 【Chemistry 21】 ,-SCH ３ , -N (CH) ３ ) ２ 、 【Chemical 22】 Selected from x is 1 or 2; A １ teeth, 【Chemistry 23】 Selected from R ２ is a hydrogen atom, a hydroxy group, an oxo group, a cyano group, a cyclopropyl group, a 1,1-dimethylcyclopropyl group, -C(=CH ２ ) CH ３ , -C(CH ３ ) (=CH ２ ) CH ３ , -CH=CH(CH ２ ) ２ CH ３ , -CH=CHCH ３ , -CH=CH-cyclopropyl group, -C(O)NH ２ , -C(O)OCH ３ , -S(O) ２ CH ３ , -OCH ３ , -CH ２ N.H. ２ , trifluoromethyl group, methyl group, trifluoromethoxy group, halogen (F, Cl, Br), -NH ２ , -NHC(O)CH ３ , -NHCH ２ CH ３ or -NHCH(CH ３ ) ２ Selected from w is 1, 2 or 3; A ２ teeth, 【Chemistry 24】 Selected from R ３ is -C(O)NH(CH ２ ) ２ CH ３ , -C(O)N(CH ３ ) ２ , -C(O)NH ２ , -C(O)NH(CH ２ ) ２ N (CH ３ ) ２ , -CH ２ C(O)NH ２ , hydrogen, -F, -Cl, -Br, cyano group, -CF ３ , -CH ３ , -CH ２ CH ３ , -CH=CH ２ , -CH ２ CN, -CH(CH ３ )-NH ２ , -CH=CH-CN, -C(O)-OH, -C(O)OCH ３ , -C(O)CH ３ , -C(CH ３ ) ２ —C(O)—OCH ３ , -C(CH ３ ) ２ -CN, oxo group, hydroxy group, cyclopropyl group, cyclobutyl group, cyclopentyl group, -NH ２ , -NH-C(O)CH ３ , -NH-S(O) ２ CH ３ , -NH-C(O)OC(CH ３ ) ３ , 【Chemistry 25】 、-S(O) ２ CH ３ 、-S(O) ２ P ３ 、-S(O) ２ NH ２ 、-OCH ２ CH ３ 、-O(CH ２ ) ２ CH ３ -OCF ３ 、 【Chemistry 26】 , -OCH ２ Cyclopropyl group, —OCH ３ , -O(CH ２ ) ３ CH ３ , -OCH ２ Phenyl group, -O-phenyl group, -(CH ２ )-OH, -(CH ２ ) ２ -OH, -(CH ２ )-OCH ３ , -(CH ２ )-OCH ２ CH ３ , -CH(OH)-CH ２ -phenyl group, -CH(OH)-CH ２ CH ３ , -CH(OH)-CH ２ CH ２ CH ３ , -CH(OH)-CH ２ CH ２ CH ２ CH ３ , -CH(OH)-CH(CH ３ ) ２ , -CH(OH)-phenyl group, -CH(OH)-CN, -CH(OH)-CH ２ -OH, -CH(OH)-CF ３ , -CH(OH)-(CH ２ ) ２ -phenyl group, ＊ -CH(OH)-C≡CH, -CH(NH ２ )-CH ２ -C(O)OH, -CH ２ -NH-S(O) ２ -CH ３ , -CH ２ -NH-(CH ２ ) ３ CH ３ , -CH ２ -NH-CH ３ , -CH ２ -N(CH ３ ) ２ , -CH ２ -NH-CH ２ CH ３ , -CH(CH ３ )-NH ２ , -CH ２ -NH ２ , -CH ２ CH ２ -NH ２ , -CH ２ NH-CH ２ -phenyl group, -CH ２ N (CH ２ CH ３ ) ２ , -CH ２ NH-cyclopropyl group, -CH ２ NH-cyclobutyl group, -CH ２ NH-cyclopentyl group, -CH ２ NH-pyridyl group, -CH ２ NH-phenyl group, -CH ２ NH-(CH ２ ) ２ -OH, -CH ２ N (CH ３ )-(CH ２ ) ２ -OH, -CH ２ NH-CH ２ -CN, -CH ２ N (CH ３ )-CH ２ -CN, -CH ２ N (CH ３ )-CH ２ -CF ３ , -CH ２ N (CH ３ )-CH ２ -CF ２ H, -CH ２ NH-CH ２ -CF ２ H, -CH ２ NH-(CH ２ ) ２ -OCH ３ , 【Chemical 27】 、-CH ２ HUNTER ３ ) ３ 、-CH ２ CH ２ HUNTER ３ ) ３ 、-CH ２ HUNTER ２ H ２ HUNTER ２ SO ３ 、-CH(CH ３ )NH-C(O)-OC(CH ３ ) ３ 、-CH ２ HUNTER ３ 、 【Chemistry 28】 、-CH ２ N+CH ２ -C(O)-NH ２ 、-CH ２ NXCH ２ -C(O)-(CH ３ ) ２ 、-CH ２ NXCH ２ -C(O)-OCH ３ 、-CH ２ NXCH ２ -C(O)-NHCH ３ 、-CH ２ NXCH ２ -C(O)-NH(CH ２ ) ２ -OCH ３ 、-CH ２ NXCH ２ -C(O)-NHCH ２ -ノデク、 【Chemical 29】 , -CH ２ NHC ２ -C(O)-NH-フェニbase、 【Chemistry 30】 , -CH ２ NH-C(O)-CH ２ NH-フェニbase, 【Chemistry 31】 or -CH ２ NH-C(O)-CH ２ NH-CH ２ CF ３ Selected from y is 1 or 2; L' is a bond, -(CH ２ ) ｋ - or -O(CH ２ ) ｋ -, k is 1 or 2, or L' is -CH=CH-(CH ２ ) ｎ -, wherein n is 0, 1 or 2; 【Chemistry 32】 In the above S2a, S2a', and S2a'', T and V are both N, or T is C and V is N, or T is N and V is C; R １ is hydrogen, -OCH ３ , -OCH ２ CH ３ , 【Chemical 33】 、-CH ２ O, -C (O) O, -C (O) O ３ ,-B2,-OCH(CH ３ ) ２ ,-O(CH ２ ) ２ HH(H) ３ ) ２ ,-O(CH ２ ) ３ CH ３ ,-O(CH ２ ) ２ OCH ３ 、 【Chemical 34】 , -O(CH ２ ) ｚ -phenyl group, -N=S(O)(CH ３ ) ２ , -CH ３ , cyclopropyl group, -N(CH ３ ) ２ , -NHCH ３ , -NH ２ , 【Chemistry 35】 、-C(CH ３ ) ２ -OH、 【Chemical 36】 , -NH(CH ２ )-NH-C(O)CH ３ , -NH(CH ２ )-morpholine, —NH—C(O)CH ３ , -NH-C(O)NHCH ３ , -NH-C(O)-N(CH ３ ) ２ , nitro group, —NH—S(O) ２ CH ３ , -N=S(O)(CH ３ ) ２ , a hydroxy group, —O—(CH ２ ) ２ -S (O) ２ CH ３ , -F, 【Chemical 37】 , a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexa group, an azetidinyl group, an azacyclopentyl group, a piperidinyl group, a piperazinyl group, an oxetane group, an oxolane group, an oxane group, a thietane group, a thiolane group, a thiane group, an azacyclobutanyloxy group, an azacyclopentyloxy group, a piperidinyloxy group, a piperazinyloxy group, an oxetanyloxy group, an oxolanyloxy group, an oxanyloxy group, a thietanyloxy group, a thiolanyloxy group, a thianyloxy group, 【Chemical 38】 ,-OCH ２ CH ２ CH ３ ,-OCH ２ CH ２ CH ２ N(CH) ３ ) ２ ,-OCH ２ CH ２ CH ２ Oh, 【Chemical 39】 ,-OCH ２ CH ２ NC(O)CH ３ ,-OCH ２ CH ２ N(CH) ３ ) ２ ,-OCH ２ CH ２ Oh, 【Chemistry 40】 ,-SCH ３ , -N (CH) ３ ) ２ 、 【Chemistry 41】 Selected from z is 1 or 2; x is 1 or 2; A １ teeth, 【Chemistry 42】 Selected from R ２ is a hydrogen atom, a hydroxy group, an oxo group, a cyano group, a cyclopropyl group, a 1,1-dimethylcyclopropyl group, -C(=CH ２ ) CH ３ , -C(CH ３ ) (=CH ２ ) CH ３ , -CH=CH(CH ２ ) ２ CH ３ , -CH=CHCH ３ , -CH=CH-cyclopropyl group, -C(O)NH ２ , trifluoromethyl group, methyl group, trifluoromethoxy group, —C(O)OCH ３ , -S(O) ２ CH ３ , -OCH ３ , -CH ２ N.H. ２ or halogen (F, Cl, Br), w is 1, 2 or 3; A ２ teeth, 【Chemistry 43】 Selected from R ３ is -C(O)NH(CH ２ ) ２ CH ３ , -C(O)N(CH ３ ) ２ , -C(O)NH ２ , -C(O)NH(CH ２ ) ２ N (CH ３ ) ２ , -CH ２ C(O)NH ２ , hydrogen, -F, -Cl, -Br, cyano group, -CF ３ , -CH ３ , -CH ２ CH ３ , -CH=CH ２ , -CH ２ CN, -CH(CH ３ )-NH ２ , -CH=CH-CN, -C(O)-OH, -C(O)OCH ３ , -C(O)CH ３ , -C(CH ３ ) ２ —C(O)—OCH ３ , -C(CH ３ ) ２ -CN, oxo group, hydroxy group, cyclopropyl group, cyclobutyl group, cyclopentyl group, -NH ２ , -NH-C(O)CH ３ , -NH-S(O) ２ CH ３ , -NH-C(O)OC(CH ３ ) ３ , 【Chemistry 44】 、-S(O) ２ CH ３ 、-S(O) ２ P ３ 、-S(O) ２ NH ２ 、-OCH ２ CH ３ 、-O(CH ２ ) ２ CH ３ -OCF ３ 、 【Chemistry 45】 , -OCH ２ Cyclopropyl group, —OCH ３ , -O(CH ２ ) ３ CH ３ , -OCH ２ Phenyl group, -O-phenyl group, -(CH ２ )-OH, -(CH ２ ) ２ -OH, -(CH ２ )-OCH ３ , -(CH ２ )-OCH ２ CH ３ , -CH(OH)-CH ２ -phenyl group, -CH(OH)-CH ２ CH ３ , -CH(OH)-CH ２ CH ２ CH ３ , -CH(OH)-CH ２ CH ２ CH ２ CH ３ , -CH(OH)-CH(CH ３ ) ２ , -CH(OH)-phenyl group, -CH(OH)-CN, -CH(OH)-CH ２ -OH, -CH(OH)-CF ３ , -CH(OH)-(CH ２ ) ２ -phenyl group, ＊ -CH(OH)-C≡CH, -CH(NH ２ )-CH ２ -C(O)OH, -CH ２ -NH-S(O) ２ -CH ３ , -CH ２ -NH-(CH ２ ) ３ CH ３ , -CH ２ -NH-CH ３ , -CH ２ -N(CH ３ ) ２ , -CH ２ -NH-CH ２ CH ３ , -CH(CH ３ )-NH ２ , -CH ２ -NH ２ , -CH ２ CH ２ -NH ２ , -CH ２ NH-CH ２ -phenyl group, -CH ２ N (CH ２ CH ３ ) ２ , -CH ２ NH-cyclopropyl group, -CH ２ NH-cyclobutyl group, -CH ２ NH-cyclopentyl group, -CH ２ NH-pyridyl group, -CH ２ NH-phenyl group, -CH ２ NH-(CH ２ ) ２ -OH, -CH ２ N (CH ３ )-(CH ２ ) ２ -OH, -CH ２ NH-CH ２ -CN, -CH ２ N (CH ３ )-CH ２ -CN, -CH ２ N (CH ３ )-CH ２ -CF ３ , -CH ２ N (CH ３ )-CH ２ -CF ２ H, -CH ２ NH-CH ２ -CF ２ H, -CH ２ NH-(CH ２ ) ２ -OCH ３ , 【Chemistry 46】 、-CH ２ HUNTER ３ ) ３ 、-CH ２ CH ２ HUNTER ３ ) ３ 、-CH ２ HUNTER ２ H ２ HUNTER ２ SO ３ 、-CH(CH ３ )NH-C(O)-OC(CH ３ ) ３ 、-CH ２ HUNTER ３ 、 【Chemistry 47】 、-CH ２ NXCH ２ -C(O)-NH ２ 、-CH ２ NXCH ２ -C(O)-(CH ３ ) ２ 、-CH ２ NXCH ２ -C(O)-OCH ３ 、-CH ２ NXCH ２ -C(O)-NHCH ３ 、-CH ２ NXCH ２ -C(O)-NH(CH ２ ) ２ -OCH ３ 、-CH ２ NXCH ２ -C(O)-NHCH ２ -ノデク、 【Chemistry 48】 , -CH ２ NHC ２ -C(O)-NH-フェニbase、 【Chemistry 49】 , -CH ２ NH-C(O)-CH ２ NH-フェニbase, 【Chemistry 50】 or -CH ２ NH-C(O)-CH ２ NH-CH ２ CF ３ Selected from Y is 1 or 2; L' is a bond, -(CH ２ ) ｋ - or -O(CH ２ ) ｋ -, k is 1 or 2, or L' is -CH=CH-(CH ２ ) ｎ -, wherein n is 0 or 1; 【Chemistry 51】 Here, in S3a, Q １ and Q. ２ are each independently CH or N; Q ３ and Q. ４ are each independently C or N, ３ and Q. ４ is C; Q ６ is CH, N, NH, O or S, Q ５ is CH, N, NH, O or S, Q １ , Q ２ , Q ３ , Q ４ , Q ５ and Q. ６ at least one of is N, NH, O or S; R １ is hydrogen, C １ -C ６ Alkyl group, halogen, -OR １ａ , a cyclopropyl group, or —CN, １ａ is hydrogen or C １ -C ６ is an alkyl group, L ２ represents a bond, -C(O)-, -C(O)O-, -C(O)NH(CH ２ ) ｏ -, -S(O) ２ -, -C(O)(CH ２ ) ｐ -, -(CH ２ ) ｐ - or O, wherein o is 0, 1 or 2, and p is an integer from 1 to 6; R ２ is hydrogen, -(CH ２ ) ｑ CH ３ , a 3- to 14-membered cycloalkyl group, a 3- to 14-membered cycloalkenyl group, a 3- to 14-membered heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group, wherein q is an integer from 1 to 5, and the 3- to 14-membered cycloalkyl group, the 3- to 14-membered cycloalkenyl group, the 3- to 14-membered heterocycloalkyl group, the 6- to 10-membered aryl group, and the 5- to 10-membered heteroaryl group are each independently, optionally selected from C １ -C ６ Alkyl group, -OH, halogen, -C(O)R ２ａ , -C(O)NR ２ｂ R ２ｃ and R ２ａ is C １ -C ６ Alkyl group or -(CH ２ ) ｒ OCH ３ wherein r is 1, 2 or 3; ２ｂ is hydrogen or C １ -C ６ is an alkyl group, ２ｃ is hydrogen or C １ -C ６ is an alkyl group, R ３ and R ４ are each independently hydrogen or C １ -C ６ is an alkyl group, ３ and R ４ At least one of R ３ and R ４ together with the atoms to which they are attached form a 3- to 6-membered cycloalkyl group; A is an optionally substituted phenyl group or an optionally substituted 5- to 6-membered heteroaryl group; 【Chemistry 52】 Here, in S4a, Q １ is CH or N, Q ４ is CH, C or N, Each Q ２ are each independently CR １ or N, Each Q ３ and Q. ５ The molecules are independently C(R ＱＣ ) ２ , N.R. ＱＮ , C(O), O, S or SO ２ and R ＱＣ are each independently hydrogen, F, Cl, Br, or a 6- to 10-membered aryl group, ＱＮ are each independently hydrogen, C １ -C ６ an alkyl group or a 6- to 10-membered aryl group; Q １ , Q ２ , Q ３ , Q ４ and Q. ５ At least one of is N, NR ＱＮ , O or SO ２ and R １ is hydrogen, C １ -C ６ An alkyl group, a halogen atom, a cyclopropyl group, a cyano group, or -OR １ａ wherein R １ａ is hydrogen or C １ -C ６ is an alkyl group, L ２ represents a bond, -C(O)-, -C(O)O-, -C(O)NH(CH ２ ) ｏ -, -S(O) ２ -, -C(O)(CH ２ ) ｐ -, -(CH ２ ) ｐ - or O, wherein o is 0, 1 or 2, and p is an integer from 1 to 6; R ２ is hydrogen, -(CH ２ ) ｑ CH ３ , a 3- to 14-membered cycloalkyl group, a 3- to 14-membered cycloalkenyl group, a 3- to 14-membered heterocycloalkyl group, a 6- to 10-membered aryl group, and a 5- to 10-membered heteroaryl group, wherein q is a multiple of 1 to 5, and the 3- to 14-membered cycloalkyl group, the 3- to 14-membered cycloalkenyl group, the 3- to 14-membered heterocycloalkyl group, the 6- to 10-membered aryl group, and the 5- to 10-membered heteroaryl group are each independently, optionally selected from C １ -C ６ Alkyl group, hydroxyl group, halogen, -C(O)R ２ａ or -C(O)NR ２ｂ R ２ｃ and R ２ａ is C １ -C ６ Alkyl group or -(CH ２ ) ｒ OCH ３ wherein r is 1, 2 or 3; ２ｂ and R ２ｃ are each independently hydrogen or C １ -C ６ is an alkyl group, R ３ and R ４ are each independently hydrogen or C １ -C ６ is an alkyl group, ３ and R ４ At least one of R ３ and R ４ together with the atoms to which they are attached form a 3- to 6-membered cycloalkyl group; A is an optionally substituted 6-membered aryl group or an optionally substituted 5- to 6-membered heteroaryl group; 【Chemistry 53】 Here, in S5a and S5a′, R １ , R ２ , R ３ , R ４ , ring A and p are as defined and explained in S5 of claim 2; 10. A compound of formula I according to claim 1, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

4. S is S6, S6', -X-S6', S6'', S6''', -X-S6''', S6a, S6a'', S6c, S6c'', -X-S6c or -X-S6c'', preferably S6c, where X is O, NH or S, preferably O; 【Chemical 54】 Here, in S6, S6', S6'', S6''', S6a, S6a'', S6c, and S6c'', R ２ is hydrogen, halogen, -OH, -CN, -NO ２ , C １ -C ６ Alkylmercapto group or -NR ａ R ｂ wherein R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ２ is C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkoxy group, C ３ -C ６ Heterocycloalkoxy group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C ４ -C ８ Cycloalkenyl groups, 4- to 7-membered heterocycloalkyl groups, 5- to 10-membered heterocycloalkenyl groups, spiroheterocycloalkyl groups, fused heterocycloalkyl groups, bridged heterocycloalkyl groups, phenyl groups, heteroaryl groups, C １ -C ６ Haloalkyl groups, -COOH, -COOR ｃ wherein R ｃ is -C １ -C ６ Alkyl group, C ３ -C ６ Alkenyl group, C ３ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group or -C ４ -C ８ is a cycloalkenyl group, R ２ is -NS(O)(R ｄ ) (R ｅ ) wherein R ｄ and R ｅ are each independently C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl group, C ４ -C ８ a cycloalkenyl group, a 6- to 10-membered aryl group, or a 5- to 10-membered heteroaryl group; R ２ is -NHC(O)-(C １ -C ６ alkyl), -NHC(O)-NR ａ R ｂ and R ａ and R ｂ each independently represents hydrogen, -C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group, R ２ is -NH-(CH ２ ) ｋ -NH-C(O)-R ａａ and R ａａ is C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ is a cycloalkyl group and k is 1 or 2; R ２ is -NH-(CH ２ ) ｉ -R ｆ wherein i is 0, 1 or 2, and R ｆ represents a 4- to 7-membered heterocycloalkyl group, a heteroaryl group, C １ -C ６ is an alkylsulfonyl group, In addition, the C １ -C ６ Alkyl group, C １ -C ６ The alkoxy, 4- to 7-membered heterocycloalkyl and heteroaryl groups are optionally substituted with halogen, —OH, oxo, —CN, —NO ２ , C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C ８ Cycloalkyl groups, 4- to 7-membered heterocycloalkyl groups, C １ -C ６ Alkoxy group, C １ -C ６ Haloalkyl group, C １ -C ６ Haloalkoxy group, C １ -C ６ Alkyl sulfonyl group, phenyl group, benzyl group, heteroaryl group, -(CH ２ )-heteroaryl group, —NHC(O)(C １ -C ６ Alkyl), C ３ -C ８ A cycloalkoxy group, a phenoxy group, a heteroaryloxy group, or -NR ａ R ｂ and R ａ and R ｂ are each independently hydrogen, C １ -C ６ Alkyl group, C ３ -C ８ Heterocycloalkyl group or C ３ -C ８ cycloalkyl groups, R ２ is -O-(CH ２ ) ｚ -phenyl group, -O-(CH ２ ) ｚ -(4- to 7-membered heterocycloalkyl), -O-(CH ２ ) ｚ -heteroaryl group, z is 0, 1 or 2, and the phenyl group, heterocycloalkyl group and heteroaryl group are optionally substituted with a group selected from -OH, a heterocycloalkyl group or a heterocycloalkenyl group, and can be substituted with a methyl group or an oxo group; Or R ２ teeth, 【Chemistry 55】 and R １ is hydrogen or -OR Ａ and R Ａ is hydrogen, C ３ -C １０ is a cycloalkyl group or a 3- to 10-membered heterocycloalkyl group, ３ -C １０ The cycloalkyl group and the 3- to 10-membered heterocycloalkyl group may optionally be substituted with one or more identical or different R ａ１ and / or R ｃ１ is replaced by Each R ａ１ are each independently C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group, １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ The aryl group, the 3- to 10-membered heterocycloalkyl group, or the 5- to 10-membered heteroaryl group each independently optionally have one or more identical or different R ｂ１ and / or R ｃ１ is replaced by Each R ｂ１ each independently represents -OR ｃ１ , -NR ｃ１ R ｃ１ , halogen, -CN, -C(O)R ｃ１ , -C(O)OR ｃ１ , -C(O)NR ｃ１ R ｃ１ , -S(O) ２ R ｃ１ , -S(O) ２ N.R. ｃ１ R ｃ１ , -NHC(O)R ｃ１ , -N(C １ -C ４ alkyl)C(O)R ｃ１ , substituted with oxo groups, said oxo groups being substituted only on non-aromatic rings; Each R ｃ１ are each independently hydrogen, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; Or R １ is C ３ -C １０ Cycloalkyl group, C ３ -C １０ Cycloalkenyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; ３ -C １０ Cycloalkyl group, C ３ -C １０ Cycloalkenyl group, C ６ -C １０ The aryl group, the 3- to 10-membered heterocycloalkyl group, or the 5- to 10-membered heteroaryl group may optionally be one or more R ａ２ and / or R ｂ２ is replaced by Each R ａ２ are each independently C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ The aryl group, the 3- to 10-membered heterocycloalkyl group, or the 5- to 10-membered heteroaryl group may optionally be one or more R ｃ２ and / or R ｂ２ is replaced by Each R ｂ２ each independently represents -OR ｃ２ , -NR ｃ２ R ｃ２ , halogen, -CN, -C(O)R ｃ２ , -C(O)OR ｃ２ , -C(O)NR ｃ２ R ｃ２ , -OC(O)R ｃ２ , -S(O) ２ R ｃ２ , -S(O) ２ N.R. ｃ２ R ｃ２ , -NHC(O)R ｃ２ , -N(C １ -C ４ alkyl)C(O)R ｃ２ , -NHC(O)OR ｃ２ , an oxo group, and =NH, and the oxo group and =NH are substituted only on non-aromatic rings; Each R ｃ２ are each independently hydrogen, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ The aryl group, the 3- to 10-membered heterocycloalkyl group, or the 5- to 10-membered heteroaryl group may optionally be one or more R ｄ２ and / or R ｅ２ is replaced by Each R ｄ２ each independently represents -OR ｅ２ , -NR ｅ２ R ｅ２ , halogen, -CN, -C(O)R ｅ２ , -C(O)OR ｅ２ , -C(O)NR ｅ２ R ｅ２ , -S(O) ２ R ｅ２ , -S(O) ２ N.R. ｅ２ R ｅ２ , -NHC(O)R ｅ２ , -N(C １ -C ４ alkyl)C(O)R ｅ２ an oxo group, said oxo group being substituted only on non-aromatic rings; Each R ｅ２ are each independently hydrogen, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ The aryl group, the 3- to 10-membered heterocycloalkyl group, or the 5- to 10-membered heteroaryl group may optionally be one or more R ｆ２ and / or R ｇ２ is replaced by Each R ｆ２ each independently represents -OR ｇ２ , -NR ｇ２ R ｇ２ , halogen, -CN, -C(O)R ｇ２ , -C(O)OR ｇ２ , -C(O)NR ｇ２ R ｇ２ , -S(O) ２ R ｇ２ , -S(O) ２ N.R. ｇ２ R ｇ２ , -NHC(O)R ｇ２ , -N(C １ -C ４ alkyl)C(O)R ｇ２ , an oxo group, said oxo group being substituted only at non-aromatic rings; Each R ｇ２ are each independently hydrogen, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; Or R １ is C ２ -C ４ Alkyl group, C ２ -C ４ alkenyl groups, ２ -C ４ Alkyl group and C ２ -C ４ The alkenyl group is optionally R ｂ３ is replaced by R ｂ３ is -C(O)R ｃ３ , -C(O)OR ｃ３ , -C(O)NR ｃ３ R ｃ３ , -C(O)NHOR ｃ３ or -C(O)N(C １ -C ４ Alkyl) OR ｃ３ Selected from Each R ｃ３ are each independently hydrogen, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ The aryl group, the 3- to 10-membered heterocycloalkyl group, or the 5- to 10-membered heteroaryl group may optionally be one or more R ｄ３ and / or R ｅ３ is replaced by Each R ｄ３ each independently represents -OR ｅ３ , -NR ｅ３ R ｅ３ , halogen, -CN, -C(O)R ｅ３ , -C(O)OR ｅ３ , -C(O)NR ｅ３ R ｅ３ , -S(O) ２ R ｅ３ , -S(O) ２ N.R. ｅ３ R ｅ３ , -NHC(O)R ｅ３ , -N(C １ -C ４ alkyl)C(O)R ｅ３ , an oxo group, said oxo group being substituted only at non-aromatic rings; Each R ｅ３ are each independently hydrogen, C １ -C ６ Alkyl group, C ２ -C ６ Alkenyl group, C ２ -C ６ Alkynyl group, C ３ -C １０ Cycloalkyl group, C ６ -C １０ an aryl group, a 3- to 10-membered heterocycloalkyl group, or a 5- to 10-membered heteroaryl group; R ３ is hydrogen, C １ -C ４ Alkyl group, -O(C １ -C ４ Alkyl), -NH ２ , -NH(C １ -C ４ Alkyl), -N(C １ -C ４ Alkyl) ２ or halogen, R ５ is selected from hydrogen, a hydroxyl group, or -NHR'; R′ is hydrogen, C １ -C ３ Alkyl groups and -C(O)C １ -C ３ selected from alkyl groups, R ４ is C １ -C ４ Alkyl group, hydroxy group, oxo group, cyano group, C １ -C ４ Alkoxy group, C １ -C ４ Haloalkyl group, C １ -C ４ Hydroxyalkyl group, hydroxy-C １ -C ４ Haloalkyl group, C ２ -C ６ Alkenyl group, -C ２ -C ６ Alkynyl group, C ３ -C ６ Cycloalkoxy group, C ３ -C ６ A cycloalkyl group, a 3- to 6-membered heterocycloalkyl group, a 3- to 6-membered hydroxyheterocycloalkyl group, a halogen, or -SO ２ -C １ -C ４ selected from alkyl groups, R ６ is hydrogen, C １ -C ４ selected from an alkyl group or a halogen; Or R ４ , R ６ are optionally substituted C together with the carbon atom to which they are attached ５ -C ６ forming a cycloalkyl group and a 5- to 6-membered heterocycloalkyl group, the heteroatoms in the 5- to 6-membered heterocycloalkyl group being selected from those containing 1, 2, 3, or 4 heteroatoms or heteroatom groups independently selected from -NH, -O-, -S-, and N; R ７ , R ８ are each independently C １ -C ６ Alkyl group, C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group or C ３ -C ６ and a cycloalkoxy group, wherein the alkyl group, the alkoxy group, the cycloalkyl group and the cycloalkoxy group are optionally selected from the group consisting of a cyano group, a hydroxy group, a C １ -C ６ Alkoxy group, C ３ -C ６ Cycloalkyl group, C ３ -C ６ substituted with cycloalkoxy groups or halogens; 10. A compound of formula I according to claim 1, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

5. R １ is hydrogen or -OR Ａ and R Ａ is hydrogen, R ２ is hydrogen, C １ -C ４ Alkyl group or -O(C １ -C ４ alkyl), and said —O(C １ -C ４ alkyl) is optionally —O(C １ -C ４ alkyl), R ３ is hydrogen, R ５ is hydrogen or -NHR', R′ is hydrogen, C １ -C ３ Alkyl groups and -C(O)C １ -C ３ selected from alkyl groups, R ４ is C １ -C ４ is a haloalkyl group, R ６ is hydrogen or halogen, Or R ４ , R ６ In S6, 【Chemistry 56】 Fragment 【Chemistry 57】 form a ring together with the carbon atoms to which they are attached, such that R ７ is C １ -C ６ is an alkyl group, R ８ is C １ -C ６ is an alkyl group, 5. A compound of formula I according to claim 4, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

6. In each S structure 【Chemistry 58】 The fragments are 【Chemistry 59】 For example, 【Chemistry 60】 and preferably 【Chemistry 61】 , more preferably 【Chemistry 62】 and And / or R ３ is hydrogen, And / or R ７ is a methyl group, 5. A compound of formula I according to claim 4, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

7. The S6, S6', S6a or S6c is any one of the following structures: 【Chemistry 63】 and / or said S6″, S6′″, S6a″ or S6c″ is of the following structure: 【Chemistry 64】 Preferably, S is the following structure: 【Chemistry 65】 More preferably, S is the following structure: 【Chemistry 66】 5. A compound of formula I according to claim 4, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

8. The L is -(CH ２ ) ｊ -, and the -(CH ２ ) ｊ One or more methylene groups of - are optionally -NR ３’ -, -O-, -CR １’ R ２’ -, -C(O)-, -S(O)-, -S(O) ２ -, -C(O)O-, -OC(O)-, -C(O)NR ３’ --, --NR ３’ C(O)-, -S(O) ２ N.R. ３’ --, --NR ３’ S (O) ２ -, vinylidene group, ethynylene group, phenyl group, 8-10 membered bicyclic arylene group, 3-7 membered saturated or partially unsaturated cycloalkylene group, 5-11 membered saturated or partially unsaturated spirocycloalkylene group, 5-11 membered saturated or partially unsaturated fused cycloalkylene group, 8-10 membered bicyclic saturated or partially unsaturated cycloalkylene group, 4-7 membered saturated or partially unsaturated heterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, 5-11 membered saturated or partially unsaturated spiroheterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur, 5-11 membered saturated or partially unsaturated fused heterocycloalkylene group having 1-2 heteroatoms independently selected from nitrogen, oxygen or sulfur. a 8- to 10-membered bicyclic saturated or partially unsaturated heterocycloalkylene group having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5- to 6-membered heteroarylene group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein the vinylidene group, ethynylene group, cycloalkylene group, heterocycloalkylene group, phenyl group, spiroheterocycloalkylene group, fused heterocycloalkylene group, spirocycloalkylene group, fused cycloalkylene group, and heteroarylene group are each independently optionally substituted with a halogen, oxo, -NR ３’ R ４’ , -OR ３’ , nitro group, -CN, C １ -C ６ Alkyl group, C ３ -C １０ Cycloalkyl group, C ３ -C １０ and heterocycloalkyl groups, the alkyl groups, cycloalkyl groups, and heterocycloalkyl groups being optionally substituted with one or more substituents selected from halogen, -OH, -NH ２ , -C.N., C. １ -C ４ Alkyl group, C ３ -C ６ cycloalkyl groups; R １’ , R ２’ each independently represents a halogen, —OH, or —NH ２ , C １ -C ４ Alkyl group, C １ -C ４ Chloroalkyl group, C １ -C ４ Hydroxyalkyl group, —O(C １ -C ４ alkyl), -NH(C １ -C ４ Alkyl), C ３ -C ６ Cycloalkyl groups, -O(C ３ -C ６ cycloalkyl), -NH(C ３ -C ６ Cycloalkyl), C ３ -C ６ Heterocycloalkyl groups, —O(C ３ -C ６ Heterocycloalkyl), -NH(C ３ -C ６ cycloalkyl), and R ３’ , R ４’ are each independently hydrogen, deuterium, or C １ -C ４ Alkyl group, C ３ -C ６ Cycloalkyl group, C ３ -C ６ heterocycloalkyl group, j is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12; Preferably, L is -(CH ２ ) ｊ -, and the -(CH ２ ) ｊ One, two, three, four or five methylene groups of - are optionally -NH-, -NCH ３ -, -O-, -C(CH ３ ) ２ -, -CHF-, -CHCF ３ -, -C(O)-, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH ３ -, -NHC(O)-, -NCH ３ C(O)-, a vinylidene group, an ethynylene group, a cyclopropylidene group, a cyclobutylidene group, a cyclopentylidene group, a cyclohexylidene group, an oxacyclopropylidene group, an oxacyclobutylidene group, an oxacyclopentylidene group, an oxacyclohexylidene group, an azacyclopropylidene group, an azacyclobutylidene group, an azacyclopentylidene group, a piperidylidene group, a piperazilidine group, a morpholinoline group, a hypomorpholino group, a phenylene group, a pyrrolidine group, a thienylene group, a furylene group, an imidazolidene group, a pyrazolylene group, a triazolylene group, a tetrazolylene group, an oxazolylene group, an isoxazolylene group, a thiazolylene group, an isothiazolylene group, a pyridylene group, a pyrimidinylidene group, a pyridazilidene group, a pyrazinylene group, 【Chemistry 67】 and the substituents are optionally substituted with a group selected from halogen, oxo, -NR ３’ R ４’ , -OR ３’ , C １ -C ４ The alkyl group is optionally substituted with one or more substituents selected from halogen, -OH, -NH ２ and R ３’ , R ４’ are each independently hydrogen, deuterium, or C １ -C ４ alkyl group, j is 2, 3, 4, 5, 6, 7, 8, 9 or 10; Preferably, L is -(CH ２ ) ｊ -, and the -(CH ２ ) ｊ One, two or three, four or five methylene groups of - are optionally -NH-, -NCH ３ -, -O-, -C(O)-, -C(O)NH-, -NHC(O)-, -NCH ３ C(O)-, -C(O)NCH ３ -, a cyclopropylidene group, a cyclobutylidene group, a cyclopentylidene group, a cyclohexylidene group, an azacyclopropylidene group, an azacyclobutylidene group, an azacyclopentylidene group, a piperidylidene group, a piperazilidene group, 【Chemistry 68】 and j is 5, 6, 7, 8, 9 or 10; 2. A compound of formula I according to claim 1, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

9. The L is 【Chemistry 69】 【Chemistry 70】 【Chemistry 71】 【Chemical 72】 【Chemical Formula 73】 【Chemical 74】 【Chemistry 75】 【Chemical Formula 76】 【Chemical 77】 【Chemical 78】 【Chemical 79】 【Chemistry 80】 【Chemistry 81】 【Chemistry 82】 【Chemistry 83】 【Chemistry 84】 【Chemistry 85】 【Chemistry 86】 【Chemistry 87】 【Chemistry 88】 【Chemistry 89】 【Chemistry 90】 【Chemistry 91】 【Chemistry 92】 【Chemistry 93】 【Chemistry 94】 【Chemistry 95】 【Chemistry 96】 【Chemistry 97】 【Chemistry 98】 【Chemistry 99】 【Chemistry 100】 【Chemistry 101】 【Chemistry 102】 【Chemistry 103】 【Chemistry 104】 【Chemistry 105】 【Chemistry 106】 【Chemistry 107】 【Chemistry 108】 【Chemistry 109】 【Chemistry 110】 【Chemistry 111】 【Chemistry 112】 【Chemistry 113】 【Chemistry 114】 【Chemistry 115】 【Chemistry 116】 【Chemistry 117】 【Chemistry 118】 【Chemistry 119】 【Chemistry 120】 【Chemistry 121】 【Chemistry 122】 【Chemistry 123】 That is, 9. A compound of formula I according to claim 8, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

10. The L is LA, 【Chemistry 124】 Here, in the LA, Ring A is a bond, C ３ -C １２ a cycloalkylene group or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, or S, the cycloalkylene group and the heterocycloalkylene group optionally containing halogen, oxo, cyano, amino, hydroxyl, C １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C １ -C ６ Hydroxyalkyl group or -O-(C １ -C ６ alkyl), Ring B is a bond, C ３ -C １２ a cycloalkylene group or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, or S, the cycloalkylene group and the heterocycloalkylene group optionally containing halogen, oxo, cyano, amino, hydroxyl, C １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C １ -C ６ Hydroxyalkyl group or -O-(C １ -C ６ alkyl), Ring C is C ３ -C １２ A cycloalkylene group or a 3- to 12-membered heterocycloalkylene group containing 1 to 2 heteroatoms selected from N, O, or S, said cycloalkylene group and heterocycloalkylene group optionally containing halogen, oxo, cyano, amino, hydroxyl, C １ -C ６ Alkyl group, C １ -C ６ Haloalkyl group, C １ -C ６ Hydroxyalkyl group or -O-(C １ -C ６ alkyl), X’’ is a bond, -NH-, -NCH ３ -, -O-, -C(CH ３ ) ２ -, -S-, -C=C-, -C≡C-, -CHF-, -CHCF ３ -, -C(O)-, -S(O)-, -S(O) ２ -, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH ３ -, -NHC(O)-, -NCH ３ C(O)- or -C(O)CH ２ O- and L ３ is -(CH ２ ) ｋ and the L ３ One or two methylene groups are optionally selected from -O-, -NH-, -C≡C-, -N(C １ -C ６ alkyl)-, -N(C １ -C ６ haloalkyl)-, -C(O)-, -N(C １ -C ６ hydroxyalkyl)- or -N(C ３ -C ８ cycloalkyl)-, k is 0, 1, 2, 3, 4, 5, 6 or 7; X''' is a bond, -NH-, -NCH ３ -, -O-, -C(CH ３ ) ２ -, -S-, -C=C-, -C≡C-, -CHF-, -CHCF ３ -, -C(O)-, -S(O)-, -S(O) ２ -, -C(O)O-, -OC(O)-, -C(O)NH-, -C(O)NCH ３ --, --CH ２ NCH ３ -, -NHC(O)- or -NCH ３ C(O)-; 10. A compound of formula I according to claim 1, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

11. In the above LA, ring A is a 3- to 6-membered saturated cycloalkylene group, ring B is a 4- to 7-membered saturated monocyclic heterocycloalkylene group containing one or two nitrogen heteroatoms, ring C is a 4- to 7-membered saturated monocyclic heterocycloalkylene group containing one or two nitrogen heteroatoms, a 7- to 11-membered spiroheterocycloalkylene group or a fused heterocycloalkylene group containing one or two nitrogen heteroatoms, X″ is a bond or —C(O)—, L ３ Ha-(CH ２ ) ｋ and k is 1, 2, 3, 4 or 5; 11. A compound of formula I according to claim 10, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

12. The LA is LA-1, 【Chemistry 125】 In the above LA-1, ring A, ring B, ring C, L ３ and X″ are as defined and explained in claim 10.

11. A compound of formula I according to claim 10, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

13. the LA is LA-2, LA-3, LA-4 or LA-5; 【Chemistry 126】 In the above LA-2, ring A is 【Chemistry 127】 wherein the a-terminus is linked to S and the b-terminus is linked to X'", and 1, 2, 3 or 4 hydrogen atoms of ring A are optionally replaced with F; X''' is -C(O)-, Ring B is 【Chemistry 128】 where the c-terminus is linked to X''' and the d-terminus is L ３ wherein 1, 2, 3 or 4 hydrogen atoms of ring B are optionally replaced with F; L ３ is -(CH ２ ) ｋ -, wherein said L ３ One or two CHs included in ２ are each independently optionally -O-, -NH- or -N(C １ -C ６ alkyl)- or ３ One -CH included in ２ CH ２ - is optionally replaced by -C≡C-, and k is 1, 2, 3 or 4; Ring C is 【Chemistry 129】 where the e end is L ３ and the f-terminus is linked to X″, and 1, 2, 3 or 4 hydrogen atoms of the ring C are optionally replaced with F; X″ is —C(O)—; 【Chemistry 130】 In the above LA-3, ring A is 【Chemistry 131】 wherein the a-terminus is linked to S and the b-terminus is linked to X'", and 1, 2, 3 or 4 hydrogen atoms of ring A are optionally replaced with F; X''' is -C(O)-, Ring B is 【Chemistry 132】 where the c-terminus is linked to X''' and the d-terminus is L ３ wherein 1, 2, 3 or 4 hydrogen atoms of ring B are optionally replaced with F; L ３ is -(CH ２ ) ｋ -, wherein said L ３ One CH included in ２ is optionally -O-, -NH- or -N(C １ -C ６ k is 1 or 2; Ring C is 【Chemistry 133】 where the e end is L ３ and the f-terminus is linked to X″, and 1, 2, 3 or 4 hydrogen atoms of the ring C are optionally replaced with F; X″ is —C(O)—; 【Chemistry 134】 Here, in the LA-4, Ring A is 【Chemistry 135】 wherein the a-terminus is linked to S and the b-terminus is linked to X'", and 1, 2, 3 or 4 hydrogen atoms of ring A are optionally replaced with F; X''' is a bond, -C(O)NH- or -C(O)NCH ３ - and Ring B is a bond; L ３ is -(CH ２ ) ｋ and the L ３ One or two methylene groups are optionally -O-, -NH-, -C(O)-, -C≡C- or -N(C １ -C ６ alkyl)-, k is 0, 1, 2, 3, 4, 5, 6 or 7; Ring C is 【Chemistry 136】 where the e end is L ３ and the f-terminus is linked to X″, and 1, 2, 3 or 4 hydrogen atoms of the ring C are optionally replaced with F; X″ is —C(O)—; 【Chemistry 137】 Here, ring A, X''', ring B, L ３ and Ring C is as defined in LA-2 or LA-3; X″ is —C(O)CH ２ and —C(O)— in X″ is linked to ring C; 11. A compound of formula I according to claim 10, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

14. In the LA-2, ring A is 【Chemistry 138】 where the a-terminus is linked to S and the b-terminus is linked to X''', And / or, in the LA-2, ring B is 【Chemistry 139】 where the c-terminus is linked to X''' and the d-terminus is L ３ Connect to And / or, in the LA-2, L ３ is -CH ２ -, -(CH ２ ) ２ -, -(CH ２ ) ３ -, -(CH ２ ) ４ --, 【Chemistry 140】 wherein the k″ end is linked to ring B and the k′ end is linked to ring C; And / or, in the LA-2, ring C is 【Chemistry 141】 where the e end is L ３ and the f end is linked to X″, And / or, in the LA-3, ring A is 【Chemistry 142】 where the a-terminus is linked to S and the b-terminus is linked to X''', And / or, in the LA-3, ring B is 【Chemistry 143】 where the c-terminus is linked to X''' and the d-terminus is L ３ Connect to And / or, in the LA-3, L ３ is -(CH ２ ) ｋ -, k is 1 or 2, And / or, in the LA-3, ring C is 【Chemistry 144】 where the e end is L ３ and the f end is linked to X″, And / or, in the LA-4, ring A is 【Chemistry 145】 where the a-terminus is linked to S and the b-terminus is linked to X''', And / or, in the above LA-4, L ３ is -CH ２ -, -(CH ２ ) ２ --, 【Chemistry 146】 wherein the k″ end is linked to ring B and the k′ end is linked to ring C; And / or, in the LA-4, ring C is 【Chemistry 147】 where the e end is L ３ and the f end is linked to X″, And / or, in the LA-5, ring A is 【Chemistry 148】 where the a-terminus is linked to S and the b-terminus is linked to X''', And / or, in the LA-5, ring B is 【Chemistry 149】 where the c-terminus is linked to X''' and the d-terminus is L ３ Connect to And / or, in the LA-5, L ３ is -(CH ２ ) - and And / or, in the LA-5, ring C is 【Chemistry 150】 where the e end is L ３ and the f end is linked to X″; 14. A compound of formula I according to claim 13, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

15. The LA is 【Chemistry 151】 【Chemistry 152】 【Chemistry 153】 【Chemistry 154】 【Chemistry 155】 , , or any one of the structures Preferably, the LA is 【Chemistry 156】 【Chemistry 157】 The structure is any one of the following:

11. A compound of formula I according to claim 10, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

16. The E is E21, 【Chemistry 158】 Here, in E21, X″ is C or N; Y″ is C, N, O or S; Q １ , Q ２ , Q ３ , Q ４ and Q. ５ are each independently CR ３ " or N, R ３ '' each independently represents hydrogen, deuterium, a hydroxyl group, an amino group, a cyano group, a halogen, C １ -C ６ Alkyl group, C ３ -C ８ Cycloalkyl groups, 3- to 8-membered heterocycloalkyl groups, 6- to 10-membered aryl groups, 5- to 10-membered heteroaryl groups, —O(C １ -C ６ alkyl), -O-(C ３ -C ８ cycloalkyl), -O-(3- to 8-membered heterocycloalkyl), N(C １ -C ６ Alkyl) １－２ , NH(C ３ -C ８ cycloalkyl), NH(3- to 8-membered heterocycloalkyl), —O—(C ６ ~C １０ -O-(aryl), -O-(5- to 10-membered heteroaryl), wherein the alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group, and heteroaryl group are optionally and independently substituted with 1 to 3 groups selected from a hydroxy group, a halogen group, a cyano group, and an amino group; m″ is 1, 2 or 3; R １ '' each independently represents hydrogen, deuterium, a hydroxyl group, an amino group, a cyano group, a halogen, C １ -C ６ Alkyl group, C ３ -C ８ Cycloalkyl groups, 3- to 8-membered heterocycloalkyl groups, 6- to 10-membered aryl groups, 5- to 10-membered heteroaryl groups, —O(C １ -C ６ alkyl), wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are optionally and independently substituted with 1 to 3 groups selected from a hydroxyl group, a halogen, a cyano group, and an amino group; R ２ '' is hydrogen, deuterium, C １ -C ６ Alkyl group or C ３ -C ６ is a cycloalkyl group, １ -C ６ Alkyl group and C ３ -C ６ The cycloalkyl group is optionally substituted with 1 to 3 groups independently selected from hydroxy, halogen, cyano, and amino.

10. A compound of formula I according to claim 1, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

17. said E21 having the structure of formula E21-1a, E21-1b, E21-1c, E21-1d, E21-1e, E21-1f, E21-1g, E21-1aa, E21-1bb, E21-1cc, E21-1dd, E21-1ee, E21-1ff or E21-1gg; 【Chemistry 159】 Here, the Q １ , Q ２ , Q ３ , Q ４ , Q ５ , R １ '', R ２ '', R ３ " and m" are as defined and explained in claim 16; 17. A compound of formula I according to claim 16, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

18. said E21 having the structure of formula E21-1h, E21-1i, E21-1j or E21-1hh, preferably E21-1h; 【Chemistry 160】 Here, R ３ " is as defined in claim 17, 18. A compound of formula I according to claim 17, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

19. R ３ '' is hydrogen, halogen, C １ -C ６ Alkyl group or -O(C １ -C ６ alkyl), １ -C ６ Alkyl group and -O(C １ -C ６ alkyl) optionally containing 1 to 3 halogens, e.g., hydrogen, F, Cl, CF ３ , -OCF ３ or -OCH ３ is replaced by 17. A compound of formula I according to claim 16, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

20. The E21 is 【Chemistry 161】 【Chemistry 162】 and Preferably, E21 is 【Chemistry 163】 The structure is any one of the following:

17. A compound of formula I according to claim 16, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

21. The compound of formula I is 【Chemistry 164】 【Chemistry 165】 【Chemistry 166】 【Chemistry 167】 【Chemistry 168】 【Chemistry 169】 【Chemistry 170】 【Chemistry 171】 【Chemistry 172】 【Chemistry 173】 【Chemistry 174】 【Chemistry 175】 【Chemistry 176】 【Chemistry 177】 【Chemistry 178】 【Chemistry 179】 【Chemistry 180】 【Chemistry 181】 【Chemistry 182】 The compound is any one of the following:

10. A compound of formula I according to claim 1, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

22. The deuterated compound is 【Chemistry 183】 【Chemistry 184】 having any one of the structures:

10. A compound of formula I according to claim 1, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof.

23. 23. A pharmaceutical composition comprising a compound according to any one of claims 1 to 22, and / or its stereoisomers, enantiomers, diastereomers, deuterated forms, hydrates, solvates, prodrugs and / or pharma- ceutically acceptable salts thereof, and a pharma- ceutically acceptable carrier, diluent or excipient.

24. A pharmaceutical composition according to claim 23 for the treatment and / or prevention of an SOS1-mediated disease or condition, or a disease or condition caused by the interaction between SOS1 and Ras or SOS1 and Rac, or cancer.

25. The cancer is Heart: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma, Lung: bronchial cancer (squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, adenocarcinoma), alveolar carcinoma (bronchiolar carcinoma), bronchial adenoma, sarcoma, lymphoma, chondroma, hamartoma, mesothelioma, Gastrointestinal esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, vasoactive intestinal peptide tumor), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma), Urinary system: kidney (adenocarcinoma, nephroblastoma, lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (spermatogonoma, teratoma, embryonal carcinoma, teratoma, choriocarcinoma, sarcoma, mesenchymal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma), Liver: liver cancer (hepatocellular carcinoma), bile duct cancer, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma, Biliary tract: gallbladder cancer, ampullary cancer, bile duct cancer, Bone: osteosarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, chondroma (osteochondral extrinsic bone disease), benign chondroma, chondroblastoma, chondromyxoid fibroma, osteoid osteoma and giant cell tumor, Nervous system: skull (osteoma, hemangioma, granuloma, xanthomas, osteitis teratoidea), meninges (meningioma, meningeal sarcoma, glioma), brain (astrocytoma, meloblastoma, glioma, ependymoma, germ cell tumor (pineal tumor), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumor), spinal cord neurofibroma, meningioma, glioma, sarcoma), Gynecology: Uterus (endometrial cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified cancer), granulosa-theca cell tumor, Sertoli stromal cell tumor, germ cell abnormality, malignant teratoma), vulva (squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, sarcoma botryoides (embryonal rhabdomyosarcoma), fallopian tube (cancer), Hematology: Blood (myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndromes), Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma), Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevus, lipoma, hemangioma, dermatofibroma, keloid, psoriasis, Adrenal gland: selected from neuroblastoma, 25. The pharmaceutical composition of claim 24.

26. the cancer is pancreatic cancer, lung cancer, colorectal cancer, cholangioepithelial cancer, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, diffuse large B-cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular carcinoma, breast cancer, ovarian cancer, prostate cancer, glioblastoma, kidney cancer, or sarcoma; 25. The pharmaceutical composition of claim 24.

27. ​​The pharmaceutical composition described in claim 23 for the treatment and / or prevention of neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), capillary malformation-arteriovenous malformation syndrome (CM-AVM), Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), Regius syndrome and hereditary gingival fibromatosis.

28. The pharmaceutical composition of claim 23 for the treatment and / or prevention of a KRAS mediated disease or condition, comprising: The pharmaceutical composition, wherein the KRAS is preferably a mutant KRAS, and the mutant KRAS is preferably one or more of KRAS G12C, KRAS G12D, KRAS G13D and KRAS G12V.

Images