Kras inhibitor compound

Abstract

The present invention relates to a compound as represented by formula (A), a pharmaceutical composition containing the compound, and the use of the compound of formula (A) for preventing and / or treating cancer, tumors, inflammatory diseases, autoimmune diseases or immune-mediated diseases.

Claims

A compound having the structure of formula (A), its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof: in: Cy a express or It may optionally be substituted with 0, 1, 2 or 3 substituents selected from halogens or C1-C3 alkyl groups; A represents 4- to 6-membered heterocycloalkylene, 4- to 6-membered heterocycloalkenylene, phenylene or 5- to 6-membered heteroarylene, each independently of the other, unsubstituted or substituted by 0, 1, 2, 3 or 4 R xA substituents; E represents a 6- to 14-membered heterocycloalkylene, 6- to 14-membered heterocycloalkenylene, which can be monocyclic, spirocyclic, bridged, annelated, and can each independently be substituted by 0, 1, 2, 3, or 4 R xE substituted; Or E can represent or wherein Cy b represents 4- to 10-membered heterocycloalkylene, 4- to 10-membered heterocycloalkenylene, which can be monocyclic, spiro, bridged, annelated, and can each independently be substituted by 0, 1, 2, 3, or 4 R xE substituents; X represents O or N-R8; L represents a single bond or a C1-C6alkylene group, any methylene of which can be replaced with a carbonyl, -NR a -, -O- or -S-, and optionally, said C1-C6alkylene group can be substituted with 0, 1, 2, 3 or 4 halogen or C1-C3alkyl, and two substituents of the same C atom can form a 3-8 membered ring with the C atom, which 3-8 membered ring optionally can contain 0, 1, 2 or 3 heteroatoms selected from N, O or S; R2represents C1-C6alkyl, -(C0-C6alkylene)-(C3-C8cycloalkyl), or -(C0-C6alkylene)-(4-8 membered heterocycloalkyl), which optionally can be substituted with 0, 1, or 2 substituents selected from: -OR a , -SR a , or -NR a R a ’; R4 represents hydrogen, C1-C6 alkyl, -(C0-C6 alkylene)-OR a -(C0-C6 alkylene)-SR a -(C0-C6 alkylene)-NR a R a '、-(C0-C6 alkylene)-(C3-C8 cycloalkyl), -(C0-C6 alkylene)-(4-12 heterocyclic alkyl), -(C0-C6 alkylene)-phenyl or -(C0-C6 alkylene)-(5-6 heteroaryl), wherein any methylene group on the C0-C6 alkylene or C1-C6 alkyl group can be independently replaced by a carbonyl group, -NR a -, -O-, or -S-, and optionally, the C0-C6 alkylene or C1-C6 alkyl group may be substituted with 0, 1, 2, 3, or 4 substituents selected from halogens or C1-C3 alkyl groups, and the two substituents of the same C atom may form a 3-8 membered ring with the C atom, the 3-8 membered ring optionally also containing 0, 1, 2, or 3 heteroatoms selected from N, O, or S; the C3-C8 cycloalkyl, 4-12 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl groups may each be independently substituted with 0, 1, 2, 3, or 4 substituents selected from halogens, oxo-, -OR-, -O ... a -SR a -NR a R a ', cyano, C1-C6 alkyl, -(C0-C3 alkylene)-(C3-C8 cycloalkyl), -(C0-C3 alkylene)-(4-8 heterocyclic alkyl), -C(O)R a -C(O)OR a -C(O)NR a R a '、-NR a C(O)R a '、-OC(O)R a '、-OC(O)NR a R a '、-NR a C(O)NR a R a '、-S(O)R a -S(O)2R a -NR a S(O)2R a Substituents of '; R5represents -OR a , -NR a R a ' or -Cy1-(R6) m ; Cy1represents C3-C 12 Cycloalkyl or 4-12 membered heterocycloalkyl, said C3-C 12 Cycloalkyl and 4-12 membered heterocycloalkyl can be monocyclic, spirocyclic, bridged, annelated; R6 represents hydrogen, halogen, oxometalate, and =NR independently. a -(C0-C6 alkylene)-OR a -(C0-C6 alkylene)-SR a -(C0-C6 alkylene)-NR a R a '、-(C0-C6 alkylene)-CN、-(C0-C6 alkylene)-C(O)OR a -(C0-C6 alkylene)-C(O)R a -(C0-C6 alkylene)-C(O)NR a R a '、-(C0-C6 alkylene)-OC(O)R a -(C0-C6 alkylene)-N(R) a )C(O)R a '、-(C0-C6 alkylene)-S(O)2R a -(C0-C6 alkylene)-S(O)R a -(C0-C6 alkylene)-S(O)(NR a )R a '、-(C0-C6 alkylene)-P(O)(OR a 2. C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; each of the above-mentioned C0-C6 alkylene, C1-C6 alkyl, C3-C8 cycloalkyl, and 4-8 membered heterocyclic alkyl groups can be independently selected from 0, 1, 2, 3, or 4 alkyl groups selected from halogen, oxo, -OR a -SR a -NR a R a Substitution with ', cyano, C1-C6 alkyl, -(C0-C3 alkylene)-(C3-C8 cycloalkyl) or -(C0-C3 alkylene)-(4-8 heterocyclic alkyl); R7, R7' each independently represent hydrogen, C1-C6alkyl, -(C0-C6alkylene)-(C3-C8cycloalkyl), or -(C0-C6alkylene)-(4-8 membered heterocycloalkyl), each of said C1-C6alkyl, -(C0-C6alkylene)-(C3-C8cycloalkyl), -(C0-C6alkylene)-(4-8 membered heterocycloalkyl) independently can be substituted with 0, 1, 2, 3, or 4 R x7 substituents; R8represents hydrogen, cyano, -C(0)OR a , -C(0)R a , -C(0)NR a R a , -S(0)2R a , -S(0)R a , -S(0)(NR a )R a , C1-C3alkyl, C3-C6cycloalkyl, or 4- to 6-membered heterocycloalkyl, each independently optionally substituted with 0, 1, or 2 R x8 ; R9 and R9' each independently represent hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl can be independently represented by 0, 1, 2, 3, or 4 R's. x9 replace; R 10 Indicates hydrogen or C1-C3 alkyl; R xA R xE R x7 R x8 R x9 Each independently represents hydrogen, halogen, oxo, =NR a -OR a -SR a -NR a R a ', cyano, -C(O)OR a -C(O)R a -C(O)NR a R a '、-S(O)2R a -S(O)R a -S(O)(NR) a )R a ', C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; Cy0 represents a 5-12 bivalent aromatic ring or a heterocyclic aromatic ring; R A H, halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), -(C0-C6 alkylene)-(4-8 heterocyclic alkyl), -(C1-C6 alkylene)-OR a -(C1-C6 alkylene)-SR a Or -(C1-C6 alkylene)-NR a R a ', any methylene group on the C0-C6 alkylene, C1-C6 alkylene, C1-C6 alkyl, and C1-C6 haloalkyl groups can be independently replaced by a carbonyl group or -NR group. a -, -O-, or -S-, and optionally, the C0-C6 alkylene, C1-C6 alkylene, C1-C6 alkyl, and C1-C6 haloalkyl groups can each be independently substituted by 0, 1, 2, 3, or 4 substituents selected from halogens or C1-C3 alkyl groups, and the two substituents of the same C atom can form a 3-8 membered ring with the C atom, the 3-8 membered ring optionally also containing 0, 1, 2, or 3 heteroatoms selected from N, O, or S; the C3-C8 cycloalkyl and 4-8 membered heterocycloalkyl groups can each be independently substituted by 0, 1, 2, 3, or 4 substituents selected from halogens, oxo-, -OR-, or -O-. a -SR a -NR a R a ', cyano, C1-C6 alkyl, -(C0-C3 alkylene)-(C3-C8 cycloalkyl) or -(C0-C3 alkylene)-(4-8 heterocyclic alkyl), -C(O)R a -C(O)OR a -C(O)NR a R a '、-NR a C(O)R a '、-OC(O)R a '、-OC(O)NR a R a '、-NR a C(O)NR a R a '、-S(O)R a -S(O)2R a -NR a S(O)2R a Substituents of '; And optionally, R on two adjacent or non-adjacent atoms on Cy0 A Together with the CyO ring atoms, a 6-10 membered ring can be formed, which can be further substituted by 0, 1, 2, 3, or 4 substituents selected from the following: halogen, C1-C3 alkyl, -OR. a -SR a Or -NR a R a '; L0 is selected from single bonds, C1-C6 alkylene groups, and C2-C6 alkenyl groups, wherein any methylene group on the C1-C6 alkylene or C2-C6 alkenyl group can be replaced by a carbonyl group or NR. a O or S, and the C1-C6 alkylene or C2-C6 alkenylene may optionally be substituted by 0, 1, 2, 3 or 4 substituents selected from the following: halogen, C1-C3 alkyl; R C Selected from H, halogens, C1-C6 alkyl groups, -(C0-C6 alkylene)-OR a -(C0-C6 alkylene)-SR a Or -(C0-C6 alkylene)-NR a R a '; R D Selected from H, C1-C6 alkyl, -(C1-C6 alkylene)-OR a -(C1-C6 alkylene)-SR a Or -(C1-C6 alkylene)-NR a R a '; R E R F Each is independently selected from H, C1-C6 alkyl, halogen, -(C0-C6 alkylene)-OR a -(C0-C6 alkylene)-SR a Or -(C0-C6 alkylene)-NR a R a '; and optionally, R E R F It can form 3-6 membered rings with the C atoms attached to them, and the 3-6 membered rings can also contain 0, 1 or 2 heteroatoms selected from N, O or S; Z represents N or CR3, Z' represents N or CR3', where R3 and R3' each independently represent hydrogen, halogen, C1-C6 alkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl) or -(C0-C6 alkylene)-CN; m and q can each independently represent 0, 1, 2, 3 or 4; R a R a Each can independently represent hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; when R a R a When connected to the same N atom, the R a and R a 'The N atom and the N atom bonded together can form a 4-8 membered ring, which may optionally contain one, two or three heteroatoms selected from N, O or S; Each of the alkyl, alkylene, cycloalkyl, cycloalkylene, heterocycloalkyl, and heteroalkylene can be independently substituted with 0, 1, 2, 3, 4, 5, or 6 halogen atoms; The compound does not include the following structures: The compound of claim 1, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, wherein, R C R D For H. The compound as described in any of the preceding claims, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, wherein... Z represents CR3, and Z' represents CR3'. The compound as described in any of the preceding claims, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, wherein... L0 is a vinylidene, a C1-C3 alkylidene, or a single bond; more preferably, L0 is a single bond. The compound as described in any of the preceding claims, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, wherein... R E R F Each is independently selected from H, C1-C6 alkyl groups, and optionally, R E R F It can form 3-6 membered rings with the C atoms bonded to it, and the rings may additionally contain 0, 1, or 2 heteroatoms selected from N, O, and S; more preferably, R E R F Each is independently selected from C1-C3 alkyl groups. The compound, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, as described in any of the preceding claims, have the structure shown in formula (B): in: --- indicates a single or double bond; X1 and X2 can each independently represent C or N; Y1, Y2, and Y3 independently represent non-bonded, single-bonded, and CR bonds, respectively. A N, NR1', O, S, where R1' and R1 independently represent C1-C6 alkyl, C1-C6 haloalkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), -(C0-C6 alkylene)-(4-8 heterocyclic alkyl), and -(C1-C6 alkylene)-OR a -(C1-C6 alkylene)-SR a Or -(C1-C6 alkylene)-NR a R a ', any methylene group on the C0-C6 alkylene, C1-C6 alkylene, C1-C6 alkyl, and C1-C6 haloalkyl groups can be independently replaced by a carbonyl group or -NR group. a -, -O-, or -S-, and optionally, the C0-C6 alkylene, C1-C6 alkylene, C1-C6 alkyl, and C1-C6 haloalkyl groups can each be independently substituted by 0, 1, 2, 3, or 4 substituents selected from halogens or C1-C3 alkyl groups, and the two substituents of the same C atom can form a 3-8 membered ring with the C atom, the 3-8 membered ring optionally also containing 0, 1, 2, or 3 heteroatoms selected from N, O, or S; the C3-C8 cycloalkyl and 4-8 membered heterocycloalkyl groups can each be independently substituted by 0, 1, 2, 3, or 4 substituents selected from halogens, oxo-, -OR-, or -O-. a -SR a -NR a R a ', cyano, C1-C6 alkyl, -(C0-C3 alkylene)-(C3-C8 cycloalkyl) or -(C0-C3 alkylene)-(4-8 heterocyclic alkyl), -C(O)R a -C(O)OR a -C(O)NR a R a '、-NR a C(O)R a '、-OC(O)R a '、-OC(O)NR a R a '、-NR a C(O)NR a R a '、-S(O)R a -S(O)2R a -NR a S(O)2R a Substituents of '; Where Y3 is CR A Optionally, R1 can be connected to R of Y3. A The substituent, together with the attached N, X1, and C atoms, forms a 6-10 membered ring, which may be further substituted by 0, 1, 2, 3, or 4 substituents selected from: halogens, C1-C3 alkyl groups, -OR groups. a -SR a Or -NR a R a '; t is selected from 0, 1, 2, or 3; Cy a A, E, X, L, R C R D R E R F ,Z,Z',R2,R4,R5,R7,R7',R9,R9',R 10 The definition is as described in any of the preceding claims. The compound of claim 6, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, wherein, X1 and X2 each represent C independently. The compound, or its isotopic derivative, stereoisomer, or pharmaceutically acceptable salt thereof, as described in any one of claims 6-7, wherein, Selected from Where Q represents CR A Alternatively, N and T represent NR1', O, or S, and optionally, when Y3 is CR A At that time, R1 can be connected to R on Y3. A The substituents, together with the ring atoms on CyO, form a 6-10 membered ring, which can be further substituted by 0, 1, 2, 3, or 4 substituents selected from: halogens, C1-C3 alkyl groups, -OR groups. a -SR a Or -NR a R a '. The compound, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, as described in any one of claims 6-8, wherein, express And optionally, R1 can be connected to R of Y3. A The substituent, together with the N, X1, and C atoms attached thereto, forms a 6-10 membered ring, which may be further substituted by 0, 1, 2, 3, or 4 substituents selected from the following: halogen, C1-C3 alkyl, -OH. The compound, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, as described in any one of claims 6-9, wherein, express The compound as described in any of the preceding claims, or its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, wherein... R A Each is independently selected from H, halogen, CN, and C1-C3 alkyl; more preferably, R A Each can be represented independently as H or F. A compound having the structure of formula (I), its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof: in: Cy a express or It may optionally be substituted with 0, 1, 2 or 3 substituents selected from halogens or C1-C3 alkyl groups; A represents a 4- to 6-membered heterocyclic alkyl group, a 4- to 6-membered heterocyclic alkenyl group, a phenylene group, or a 5- to 6-membered heterocyclic aryl group, wherein each of the 4- to 6-membered heterocyclic alkyl group, the 4- to 6-membered heterocyclic alkenyl group, the phenylene group, or the 5- to 6-membered heterocyclic aryl group can be independently represented by 0, 1, 2, 3, or 4 R's. xA replace; E represents a 6- to 14-membered heterocyclic alkyl group or a 6- to 14-membered heterocyclic alkenyl group, wherein the 6- to 14-membered heterocyclic alkyl group or the 6- to 14-membered heterocyclic alkenyl group can be monocyclic, spirocyclic, bridged, or fused, and can be independently bounded by 0, 1, 2, 3, or 4 R groups. xE replace; Or E can represent or Cy b The term represents 4- to 10-membered heterocyclic alkyl groups and 4- to 10-membered heterocyclic alkenyl groups, which can be monocyclic, spirocyclic, bridged, or fused rings, and can be independently bounded by 0, 1, 2, 3, or 4 R groups. xE replace; X represents O or N-R8; L represents a single bond or a C1-C6 alkylene group, and any methylene group on the C1-C6 alkylene group can be replaced by a carbonyl group or -NR. a -, -O-, or -S-, and optionally, the C1-C6 alkylene group may be substituted with 0, 1, 2, 3, or 4 halogens or C1-C3 alkyl groups, and two substituents of the same C atom may form a 3-8 membered ring with the C atom, the 3-8 membered ring optionally containing 0, 1, 2, or 3 heteroatoms selected from N, O, or S; R1 represents C1-C6 alkyl, C1-C6 haloalkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), -(C0-C6 alkylene)-(4-8 membered heterocyclic alkyl), -(C1-C6 alkylene)-OR a -(C1-C6 alkylene)-SR a Or -(C1-C6 alkylene)-NR a R a ', any methylene group on the C0-C6 alkylene, C1-C6 alkylene, C1-C6 alkyl, and C1-C6 haloalkyl groups can be independently replaced by a carbonyl group or -NR group. a -, -O-, or -S-, and optionally, the C0-C6 alkylene, C1-C6 alkylene, C1-C6 alkyl, and C1-C6 haloalkyl groups can each be independently substituted by 0, 1, 2, 3, or 4 substituents selected from halogens or C1-C3 alkyl groups, and the two substituents of the same C atom can form a 3-8 membered ring with the C atom, the 3-8 membered ring optionally also containing 0, 1, 2, or 3 heteroatoms selected from N, O, or S; the C3-C8 cycloalkyl and 4-8 membered heterocycloalkyl groups can each be independently substituted by 0, 1, 2, 3, or 4 substituents selected from halogens, oxo-, -OR-, or -O-. a -SR a -NR a R a ', cyano, C1-C6 alkyl, -(C0-C3 alkylene)-(C3-C8 cycloalkyl) or -(C0-C3 alkylene)-(4-8 heterocyclic alkyl), -C(O)R a -C(O)OR a -C(O)NR a R a '、-NR a C(O)R a '、-OC(O)R a '、-OC(O)NR a R a '、-NR a C(O)NR a R a '、-S(O)R a -S(O)2R a -NR a S(O)2R a Substituents of '; R2 represents a C1-C6 alkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), or -(C0-C6 alkylene)-(4-8 heterocyclic alkyl), which may optionally be substituted with 0, 1, or 2 substituents selected from the following: -OR a -SR a Or -NR a R a '; R3 and R3' each independently represent hydrogen, halogen, C1-C6 alkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl) or -(C0-C6 alkylene)-CN; R4 represents hydrogen, C1-C6 alkyl, -(C0-C6 alkylene)-OR a -(C0-C6 alkylene)-SR a -(C0-C6 alkylene)-NR a R a '、-(C0-C6 alkylene)-(C3-C8 cycloalkyl), -(C0-C6 alkylene)-(4-12 heterocyclic alkyl), -(C0-C6 alkylene)-phenyl or -(C0-C6 alkylene)-(5-6 heteroaryl), wherein any methylene group on the C0-C6 alkylene or C1-C6 alkyl group can be independently replaced by a carbonyl group, -NR a -, -O-, or -S-, and optionally, the C0-C6 alkylene or C1-C6 alkyl group may be substituted with 0, 1, 2, 3, or 4 substituents selected from halogens or C1-C3 alkyl groups, and the two substituents of the same C atom may form a 3-8 membered ring with the C atom, the 3-8 membered ring optionally also containing 0, 1, 2, or 3 heteroatoms selected from N, O, or S; the C3-C8 cycloalkyl, 4-12 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl groups may each be independently substituted with 0, 1, 2, 3, or 4 substituents selected from halogens, oxo-, -OR-, -O ... a -SR a -NR a R a ', cyano, C1-C6 alkyl, -(C0-C3 alkylene)-(C3-C8 cycloalkyl), -(C0-C3 alkylene)-(4-8 heterocyclic alkyl), -C(O)R a -C(O)OR a -C(O)NR a R a '、-NR a C(O)R a '、-OC(O)R a '、-OC(O)NR a R a '、-NR a C(O)NR a R a '、-S(O)R a -S(O)2R a -NR a S(O)2R a Substituents of '; R5 represents -OR a -NR a R a 'Or -Cy1-(R6)' m ; Cy1 represents C3-C 12 Cycloalkyl or 4-12 membered heterocycloalkyl, wherein C3-C 12 Cycloalkyl and 4-12 membered heterocyclic alkyl groups can be monocyclic, spirocyclic, bridged, or fused. R6 represents hydrogen, halogen, oxometalate, and =NR independently. a -(C0-C6 alkylene)-OR a -(C0-C6 alkylene)-SR a -(C0-C6 alkylene)-NR a R a '、-(C0-C6 alkylene)-CN、-(C0-C6 alkylene)-C(O)OR a -(C0-C6 alkylene)-C(O)R a -(C0-C6 alkylene)-C(O)NR a R a '、-(C0-C6 alkylene)-OC(O)R a -(C0-C6 alkylene)-N(R) a )C(O)R a '、-(C0-C6 alkylene)-S(O)2R a -(C0-C6 alkylene)-S(O)R a -(C0-C6 alkylene)-S(O)(NR a )R a '、-(C0-C6 alkylene)-P(O)(OR a 2. C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; each of the above-mentioned C0-C6 alkylene, C1-C6 alkyl, C3-C8 cycloalkyl, and 4-8 membered heterocyclic alkyl groups can be independently selected from 0, 1, 2, 3, or 4 alkyl groups selected from halogen, oxo, -OR a -SR a -NR a R a Substitution with ', cyano, C1-C6 alkyl, -(C0-C3 alkylene)-(C3-C8 cycloalkyl) or -(C0-C3 alkylene)-(4-8 heterocyclic alkyl); R7 and R7' each independently represent hydrogen, C1-C6 alkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), or -(C0-C6 alkylene)-(4-8 heterocyclic alkyl), wherein the C1-C6 alkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), or -(C0-C6 alkylene)-(4-8 heterocyclic alkyl) can each be represented by 0, 1, 2, 3, or 4 R's. x7 replace; R8 represents hydrogen, cyano group, -C(O)OR a -C(O)R a -C(O)NR a R a '、-S(O)2R a -S(O)R a -S(O)(NR) a )R a ', C1-C3 alkyl, C3-C6 cycloalkyl, or 4-6 membered heterocyclic alkyl, wherein each of the C1-C3 alkyl, C3-C6 cycloalkyl, and 4-6 membered heterocyclic alkyl can be independently represented by 0, 1, or 2 R's. x8 replace; R9 and R9' each independently represent hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl, wherein each of the C1-C6 alkyl, C2-C6 alkenyl, C2-C6 ynyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl can be independently represented by 0, 1, 2, 3, or 4 R's. x9 replace; R 10 Indicates hydrogen or C1-C3 alkyl; R xA R xE R x7 R x8 R x9 Each independently represents hydrogen, halogen, oxo, =NR a -OR a -SR a -NR a R a ', cyano, -C(O)OR a -C(O)R a -C(O)NR a R a '、-S(O)2R a -S(O)R a -S(O)(NR) a )R a ', C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; R a R a Each can independently represent hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; when R a R a When connected to the same N atom, the R a and R a 'The N atom and the N atom bonded together can form a 4-8 membered ring, which may optionally contain one, two or three heteroatoms selected from N, O or S; m represents 0, 1, 2, 3, or 4; Each of the alkyl, alkylene, cycloalkyl, cycloalkylene, heterocycloalkyl, and heteroalkylene can be independently substituted with 0, 1, 2, 3, 4, 5, or 6 halogen atoms; The compound does not include the following structures: The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein Cy a express or It may optionally be substituted with 0, 1, 2 or 3 substituents selected from halogens or C1-C3 alkyl groups; preferably, Cy a express or It may optionally be substituted with 0, 1, 2 or 3 substituents selected from halogens or C1-C3 alkyl groups; more preferably, Cy a express or The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... A represents a 4- to 6-membered heterocyclic alkyl group, a 4- to 6-membered heterocyclic alkenyl group, a phenylene group, or a 5-membered heteroaryl group, wherein each of the 4- to 6-membered heterocyclic alkyl group, the 4- to 6-membered heterocyclic alkenyl group, the phenylene group, and the 5-membered heteroaryl group can be independently represented by 0, 1, or 2 R's. xA Replacement; preferably, R xA Each is independently selected from hydroxyl, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; more preferably, R xA The number of is 0; more preferably, A represents a 6-membered heterocyclic alkyl group, a 6-membered heterocyclic alkenyl group, a phenylene group, or a thiazolyl group; or preferably, A represents a morpholino group. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... E represents a 6- to 14-membered heterocyclic alkyl group or a 6- to 14-membered heterocyclic alkenyl group, wherein the 6- to 14-membered heterocyclic alkyl group or the 6- to 14-membered heterocyclic alkenyl group can be monocyclic, spirocyclic, bridged, or fused, and can be independently bounded by 0, 1, 2, 3, or 4 R groups. xE Substitution; preferably, E represents a 6- to 14-membered heterocyclic alkyl group, which can be monocyclic, spirocyclic, bridged, or fused, and can be substituted with 0, 1, or 2 Rs. xE Replacement; preferably, R xE Each is independently selected from oxo- and C1-C3 alkyl groups; preferably, R xE The number of substituents is 0. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... E has the structure shown in equation (e): In this context, Q can independently represent -CH2-, -O-, -S-, or -NH-. a, b, c, and d each independently represent 0, 1, 2, 3, 4, and 5; p and q each independently represent 0, 1, 2, 3, and 4; Preferably, Q independently represents -CH2- or -O-, and / or R. xE Each can be independently represented as either oxo or C1-C3 alkyl; Preferably, a, b, c, and d each independently represent 1, 2, and 3, and / or p and q each independently represent 0, 1, and 2. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... E can represent or Cy b The term represents 4- to 10-membered heterocyclic alkyl groups and 4- to 10-membered heterocyclic alkenyl groups, which can be monocyclic, spirocyclic, bridged, or fused rings, and can be independently bounded by 0, 1, 2, 3, or 4 R groups. xE Replacement; preferably, E may represent Cy b The term represents 4- to 10-membered heterocyclic alkyl groups and 4- to 10-membered heterocyclic alkenyl groups, which can be monocyclic, spirocyclic, bridged, or fused rings, and can have 0, 1, or 2 R groups. xE Replacement; preferably, R xE Each is independently selected from oxo and C1-C3 alkyl groups. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... E represents: or The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... X represents N-R8. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... L represents a single bond, a C1-C3 alkylene group, or a C1-C3 haloalkylene group, wherein any methylene group on the C1-C3 alkylene group or C1-C3 haloalkylene group can be replaced by a carbonyl group or -NR. a -, -O-, or -S-; preferably, L represents a single bond, -CH2-, -C(H)F-, -CF2-, -C(O)-, or -NR. a -, -O-, or -S-; more preferably, L represents a single bond, -CH2-, or -O-. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R1 represents C1-C6 alkyl, C1-C6 haloalkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), -(C0-C6 alkylene)-(4-8 membered heterocyclic alkyl), -(C1-C6 alkylene)-OR a -(C1-C6 alkylene)-SR a Or -(C1-C6 alkylene)-NR a R a Preferably, R1 represents C1-C6 alkyl, C1-C6 haloalkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), -(C0-C6 alkylene)-(4-8 heterocyclic alkyl); preferably, R1 represents C1-C6 alkyl or C1-C6 haloalkyl; more preferably, R1 represents ethyl or -CH2CF3. The compound, its isotopic derivative, stereoisomer, or pharmaceutically acceptable salt thereof as described in any one of claims 1-20, wherein, R1 represents C4-C8 cycloalkyl, 4-8 membered heterocycloalkyl, -(C1-C6 alkylene)-Cyx, or -(C1-C6 alkylene)-het-Cyx, where het represents O, S, or NR. a Cyx represents a C3-C8 cycloalkyl or a 4-8 membered heterocycloalkyl, wherein the C4-C8 cycloalkyl, 4-8 membered heterocycloalkyl, and Cyx in R1 may optionally be 0, 1, 2, or 3 selected from halogen, oxo, -OR a -SR a -NR a R a The substituents are ', cyano, C1-C6 alkyl, C3-C8 cycloalkyl or 4-8 heterocyclic alkyl; preferably, R1 represents C4-C6 cycloalkyl or 4-6 heterocyclic alkyl, wherein the C4-C6 cycloalkyl or 4-6 heterocyclic alkyl may optionally be substituted by 0, 1 or 2 substituents selected from halogen, cyano, C1-C6 alkyl, C3-C8 cycloalkyl or 4-8 heterocyclic alkyl. The compound, its isotopic derivative, stereoisomer, or pharmaceutically acceptable salt thereof as described in any one of claims 1-20, wherein, R1 indicates: ethyl group, -CH2CF3, The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R2 represents a C1-C6 alkyl group, wherein the C1-C6 alkyl group may be substituted with 0 or 1 -ORa; preferably, R2 represents 1-methoxyethyl; more preferably, R2 represents Where * indicates that R2 is connected to the site in the general formula that is connected to it. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R3 and R3' each independently represent hydrogen, halogen, and C1-C6 alkyl; preferably, R3 and R3' are H. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R4 represents hydrogen, -(C0-C6 alkylene)-OR a -(C0-C6 alkylene)-SR a Or -(C0-C6 alkylene)-NR a R a Preferably, R4 represents hydrogen, -OR a -SR a Or -NR a R a Preferably, R4 represents H. The compound, its isotopic derivative, stereoisomer, or pharmaceutically acceptable salt thereof as described in any one of claims 1-25, wherein, R4 represents H, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), -(C0-C6 alkylene)-(4-12 membered heterocyclic alkyl), -(C0-C6 alkylene)-OR a -(C0-C6 alkylene)-SR a Or -(C0-C6 alkylene)-NR a R a ', wherein any methylene group on the C0-C6 alkylene group can be replaced with a carbonyl group, -NR a -, -O-, or -S-; wherein, the C3-C8 cycloalkyl and 4-12 membered heterocycloalkyl groups are each independently selectable by 0, 1, 2, 3, or 4 groups selected from halogen, oxo, -OR a -SR a -NR a R a Substituents such as cyano, C1-C6 alkyl, -(C0-C3 alkylene)-(C3-C8 cycloalkyl), or -(C0-C3 alkylene)-(4-8 heterocyclic alkyl) are used; preferably, R4 represents H, -O-(C2-C3 alkylene)-(C3-C8 cycloalkyl), or -NR. a -(C2-C3 alkylene)-(C3-C8 cycloalkyl), -O-(C2-C3 alkylene)-(4-8 membered heterocyclic alkyl), -NR a -(C2-C3 alkylene)-(4-8 membered heterocyclic alkylene), OR a -SR a Or NR a R a The C3-C8 cycloalkyl and 4-8 heterocyclic alkyl groups can each be independently selected from halogen, oxo, -OR by 0, 1, 2 or 3. a -SR a -NR a R a Substitution with cyano, C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; more preferably, R4 represents H, -O-(C2-C3 alkylene)-(C3-C8 cycloalkyl), -O-(C2-C3 alkylene)-(4-8 membered heterocyclic alkyl), OR a Or NR a R a Each of the C3-C8 cycloalkyl groups and 4-8 heterocyclic alkyl groups can be independently substituted by 0, 1 or 2 substituents selected from halogens, oxo groups, and C1-C6 alkyl groups. The compounds, isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in claims 1-25, wherein, R4 represents: H, -OH, or The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R5 represents -Cy1-(R6) m . The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... Cy1 represents a C3-C8 cycloalkyl or a 4-8 membered heterocyclic alkyl, wherein the ring can be a monocyclic, spirocyclic, bridged, or fused ring; preferably, Cy1 represents a C5-C6 cycloalkyl or a 5-6 membered heterocyclic alkyl; more preferably, Cy1 represents a 5-6 membered heterocyclic alkyl; even more preferably, the N atom on the Cy1 ring is connected to L. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... Cy1 indicates or Furthermore, Cy1 can have m substituents selected from R5; more preferably, Cy1 represents or Furthermore, Cy1 can have m substituents selected from R5. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R6 represents hydrogen, halogen, oxometalate, and =NR independently. a -OR a -SR a -NR a R a ', cyano, -C(O)OR a -C(O)R a -C(O)NR a R a '、-S(O)2R a -S(O)R a -S(O)(NR) a )R a '、-P(O)(OR a 2. C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; each of the above-mentioned C1-C6 alkyl, C3-C8 cycloalkyl, and 4-8 membered heterocyclic alkyl groups can be independently selected from 0, 1, 2, 3, or 4 alkyl groups selected from halogen, oxo, -OR a -SR a -NR a R a Substituents of cyano, C1-C6 alkyl, -(C0-C3 alkylene)-C3-C8 cycloalkyl, or -(C0-C3 alkylene)-4-8 heterocyclic alkyl; preferably, R6 independently represents hydrogen, oxo, =NR a C1-C6 alkyl groups; each of the C1-C6 alkyl groups may independently be selected from 0, 1, 2 or 3 alkyl groups selected from halogen, oxo, -OR a -SR a -NR a R a Substituents of '; more preferably, R6 independently represents hydrogen, oxy, =NR a C1-C3 alkyl, -C(O)R a Or -S(O)2R a . The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... Cy1-(R6) m express or The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R7 represents hydrogen, C1-C6 alkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), or -(C0-C6 alkylene)-(4-8 heterocyclic alkyl), wherein each of the C1-C6 alkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl), and -(C0-C6 alkylene)-(4-8 heterocyclic alkyl) can be independently represented by 0, 1, 2, 3, or 4 Rs. x7 Substitution, R7' represents hydrogen; preferably, R x7 Each is independently selected from hydrogen, halogen, and C1-C6 alkyl; preferably, R x7 R7 represents hydrogen; more preferably, R7 represents hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl or 4-8 membered heterocyclic alkyl, and R7' represents hydrogen; more preferably, R7 represents hydrogen, C1-C6 alkyl or C3-C8 cycloalkyl, and R7' represents hydrogen; even more preferably, R7 represents hydrogen, isopropyl or cyclopentyl, and R7' represents hydrogen. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R8 represents hydrogen, -C(O)OR a -C(O)R a -C(O)NR a R a '、-S(O)2R a -S(O)R a -S(O)(NR) a )R a ', C1-C3 alkyl, C3-C6 cycloalkyl or 4-6 membered heterocyclic alkyl; preferably, R8 represents hydrogen, -C(O)R a -S(O)2R a Methyl or cyclopropyl. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R8 represents hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl, or 4-6 membered heterocyclic alkyl, wherein each of the C1-C3 alkyl, C3-C6 cycloalkyl, and 4-6 membered heterocyclic alkyl can be independently represented by 0, 1, or 2 R's. x8 replace. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R8 represents hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl, or 4-6 membered heterocyclic alkyl; preferably, R8 represents hydrogen, methyl, or cyclopropyl. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R9 represents hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl or 4-8 membered heterocyclic alkyl, and R9' represents hydrogen; preferably, R9 represents hydrogen, methyl or cyclopropyl, and R9' represents hydrogen. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R 10 It represents hydrogen. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R a R a Each of the following can independently represent hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; preferably, R a R a Each can independently represent hydrogen or C1-C6 alkyl; more preferably, R a R a Each can be used independently to represent either hydrogen or a C1-C3 alkyl group. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... m represents 0, 1, 2, or 3. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... Compounds with structure (I) have structure (II): Among them: Cy a A, X, L, Q, R xE R1, R5, R7, R9, a, b, c, d, p, q are as described in any of the preceding claims. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... In the structure of formula (II): Cya said or It may optionally be substituted with 0, 1, 2 or 3 substituents selected from halogens or C1-C3 alkyl groups; A represents a 4- to 6-membered heterocyclic alkyl group, a 4- to 6-membered heterocyclic alkenyl group, a phenylene group, or a 5-membered heteroaryl group, wherein each of the 4- to 6-membered heterocyclic alkyl group, the 4- to 6-membered heterocyclic alkenyl group, the phenylene group, and the 5-membered heteroaryl group can be independently represented by 0, 1, or 2 R's. xA replace; X represents O or N-R8; L represents a single bond, -(C1-C3)alkylene- or -(C1-C3)haloalkylene-, wherein any methylene group on the -(C1-C3)alkylene- or -(C1-C3)haloalkylene- can be replaced by a carbonyl group, -NR a -、-O- or -S-; Q can independently represent -CH2-, -O-, -S-, or -NH-; a, b, c, and d each independently represent 1, 2, or 3; p and q can each independently represent 0, 1, or 2; R xE Each is independently selected from oxo, C1-C3 alkyl groups. R1 represents a C1-C6 alkyl or a C1-C6 haloalkyl; R5 represents -OR a -NR a R a 'Or -Cy1-(R6)' m ; Cy1 represents a C3-C8 cycloalkyl or a 4-8 membered heterocyclic alkyl, wherein the C3-C8 cycloalkyl or 4-8 membered heterocyclic alkyl can be monocyclic, spirocyclic, bridged, or fused. R6 represents hydrogen, halogen, oxometalate, and =NR independently. a -OR a -SR a -NR a R a ', cyano, -C(O)OR a -C(O)R a -C(O)NR a R a '、-S(O)2R a -S(O)R a -S(O)(NR) a )R a '、-P(O)(OR a 2. C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; each of the above-mentioned C1-C6 alkyl, C3-C8 cycloalkyl, and 4-8 membered heterocyclic alkyl groups can be independently selected from 0, 1, 2, 3, or 4 alkyl groups selected from halogen, oxo, -OR a -SR a -NR a R a Substitution with ', cyano, C1-C6 alkyl, -(C0-C3 alkylene)-C3-C8 cycloalkyl or -(C0-C3 alkylene)-4-8 heterocyclic alkyl groups; R7 represents hydrogen, C1-C6 alkyl, -(C0-C6 alkylene)-(C3-C8 cycloalkyl) or -(C0-C6 alkylene)-(4-8 heterocyclic alkyl); R8 represents hydrogen, -C(O)OR a -C(O)R a -C(O)NR a R a '、-S(O)2R a -S(O)R a -S(O)(NR) a )R a ', C1-C3 alkyl or C3-C6 cycloalkyl; R9 represents hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; R xA Each is independently selected from hydrogen, hydroxyl, halogen, C1-C3 alkyl, or C1-C3 haloalkyl; R a R a Each can independently represent hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; when R a R a When connected to the same N atom, the R a and R a 'The N atom and the N atom bonded together can form a 4-8 membered ring, which may optionally contain one, two or three heteroatoms selected from N, O or S; m represents 0, 1, 2, 3, or 4; The alkyl, alkylene, cycloalkyl, cycloalkylene, heterocycloalkyl, and heteroalkylene can each be independently substituted with 0, 1, 2, 3, 4, 5, or 6 halogen atoms. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R8 represents hydrogen, C1-C3 alkyl, or C3-C6 cycloalkyl. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... Compounds with structure (I) have structure (III): Among them: Cy a A, R1, L, Cy1, R6, R7, Q, R8, R9, a, b, c, d, m as described in any of the preceding claims. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... In the structure of equation (III): Cy a express or A represents a 4- to 6-membered heterocyclic alkyl group, a 4- to 6-membered heterocyclic alkenyl group, a phenylene group, or a 5-membered heteroaryl group, wherein the 4- to 6-membered heterocyclic alkyl group, the 4- to 6-membered heterocyclic alkenyl group, the phenylene group, or the 5-membered heteroaryl group may be substituted with 0, 1, or 2 hydroxyl groups, halogens, C1-C3 alkyl groups, or C1-C3 haloalkyl groups. Q can represent -CH2- or -O- independently; a, b, c, and d each independently represent 1, 2, or 3; L indicates a single bond, -CH2-, or -O-. R1 represents ethyl or trifluoroethyl; Cy1 represents a 5-6 membered heterocyclic alkyl group; R6 represents hydrogen, oxygen, and =NR independently. a C1-C3 alkyl groups; R7 represents hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, or 4-8 membered heterocyclic alkyl; R8 represents hydrogen, -C(O)R a -S(O)2R a methyl or cyclopropyl; R9 represents hydrogen, methyl, or cyclopropyl; m represents 0, 1, 2, or 3; The alkyl, alkylene, cycloalkyl, cycloalkylene, heterocycloalkyl, and heteroalkylene can each be independently substituted with 0, 1, 2, 3, 4, 5, or 6 halogen atoms. The compound, its isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof as described in any of the preceding claims, wherein... R8 represents hydrogen, methyl, or cyclopropyl. Compounds, their isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof, said compounds having a structure selected from: Pharmaceutical compositions comprising the compounds of any of the preceding claims, their isotopic derivatives, stereoisomers, or pharmaceutically acceptable salts thereof. Use of the compound, its isotope derivative, stereoisomer, or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 49, in the preparation of a medicament for the prevention and / or treatment of cancer, tumors, inflammatory diseases, autoimmune diseases, or immune-mediated diseases.

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