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KR-20260062970-A - Macrocyclic compounds, methods for their preparation, and uses

KR20260062970AKR 20260062970 AKR20260062970 AKR 20260062970AKR-20260062970-A

Abstract

Compounds as represented by formula (I) or stereoisomers thereof, or pharmaceutically acceptable salts, solvates, or prodrugs thereof, pharmaceutical compositions comprising these, and their use in the manufacture of drugs for preventing and/or treating diseases or disorders (e.g., cancer) associated with RAS protein activity.

Inventors

  • 자오, 지천
  • 저우, 후성
  • 량, 타오
  • 루, 옌동
  • 장, 타오
  • 린, 충란
  • 펑, 링
  • 란, 중
  • 루, 창

Assignees

  • 젠플리트 테라퓨틱스 (상하이) 아이엔씨.

Dates

Publication Date
20260507
Application Date
20240830
Priority Date
20230901

Claims (16)

  1. As a compound represented by formula (I), or a stable deuterated derivative thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof: (I) In the equation, Ring A is or And; is a phenyl, pentagonal or hexagonal heteroaryl or a pentagonal or hexagonal heterocyclil; one or two ring atoms of the pentagonal or hexagonal heteroaryl are heteroatoms selected from nitrogen, oxygen, or sulfur; one or two ring atoms of the pentagonal or hexagonal heterocyclil are heteroatoms selected from nitrogen, oxygen, or sulfur; the pentagonal or hexagonal heterocyclil is a fully saturated heterocyclil or a partially unsaturated heterocyclil; or where W1 is CH, C, or N; W2 is CH, C, or N; W3 is CR13 , O, S, N, or NH; W4 is CR13 , O, S, N, or NH; W5 is absent or O or CR14 ; indicates the connection point with the left part; W 6 is selected from CR 13 or N; X is , or And; Y1 is N or CH; where N can be oxidized (N + -O - ); Y₂ is N or CH; where N can be oxidized (N + -O - ); R 42 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; R 43 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; or R 42 and R 43 together form a substituted or unsubstituted C 3-6 cycloalkyl or a substituted or unsubstituted ternary to octary heterocyclyl with a connected carbon atom; R 40 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; R 41 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; or R 40 and R 41 are connected to form -CH 2 - or -CH 2CH 2 -; wherein -CH 2 - or -CH 2CH 2 - is optionally substituted by one or more groups selected from deuterium, halogen, C 1-6 alkyl, C 1-6 alkyl halides, and C 1-6 alkyl deuteriumides; Ring A In the case where L1 is -N( R00 )C(=O)-, -N( R00 )C(=O)-O-, -C1-4 alkyl-N( R00 )C(=O)-, -C(=O)N( R00 ) -C1-4 alkyl-, -C1-4 alkyl-N( R00 )C(=S)-, -substituted or unsubstituted C1-6 alkyl-O-, -substituted or unsubstituted C2-6 alkenyl-O-, -substituted or unsubstituted C3-6 cycloalkyl, -substituted or unsubstituted ternary to octary heterocyclyl, -substituted or unsubstituted C6-10 aryl, -substituted or unsubstituted pentary or sixary monocyclic heteroaryl, -substituted or unsubstituted octary to tenary bicyclic heteroaryl, -L2 -Substituted or unsubstituted C 6-10 aryl-, -L 2 -substituted or unsubstituted 5- or 6-membered monocyclic heteroaryl-, -L 2 -substituted or unsubstituted 8- or 10-membered bicyclic heteroaryl-, or -L 2 -substituted or unsubstituted 3 to 8-membered heterocyclic; L2 is a C3-6 cycloalkyl, ternary to octary heterocyclyl, -O-, -C1-4 alkyl-, -N( R00 )-, -C(=O)-, -CR09 = CR10- , -N( R00 )C(=O)- or -N( R00 )C(=S)-; Ring A In the case of; If at least one of W1 , W2 , W3 , W4 , and W5 is a heteroatom selected from O, S, N, or NH; L1 is -N( R00 )C(=O)-, -N( R00 )C(=O)-O-, -C1-4 alkyl-N( R00 )C(=O)-, -C(=O)N( R00 ) -C1-4 alkyl-, -C1-4 alkyl-N( R00 )C(=S)-, -substituted or unsubstituted C1-6 alkyl-O-, -substituted or unsubstituted C2-6 alkenyl-O-, substituted or unsubstituted C3-6 cycloalkyl, substituted or unsubstituted ternary to octary heterocyclyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted pentary or sixary monocyclic heteroaryl, substituted or unsubstituted octary to tenary bicyclic heteroaryl, -L2 -substituted or Unsubstituted C 6-10 aryl-, -L 2 -substituted or unsubstituted 5- or 6-membered monocyclic heteroaryl-, or -L 2 -substituted or unsubstituted 3- to 8-membered heterocyclic-; L 2 is -O-, -C 1-4 alkyl-, -N(R 00 )-, -C(=O)-, -CR 09 =CR 10 -, -N(R 00 )C(=O)- or -N(R 00 )C(=S)- or; or, Where W1 and W2 are both C; and W3 , W4 , and W5 are all CH, L1 is -N( R00 )C(=O)-O-, -C1-4 alkyl-N( R00 )C(=O)-, -N( R00 )C(=O) -C1-4 alkyl-, -C1-4 alkyl-N( R00 )C(=S)-, -substituted or unsubstituted C1-6 alkyl-O- or -substituted or unsubstituted C2-6 alkenyl-O-; R 00 is hydrogen or C 1-6 alkyl; R1 is hydrogen, deuterium, halogen, hydroxy, C1-6 alkyl, or a substituted or unsubstituted C1-6 heteroalkyl; R2 is hydrogen, deuterium, halogen, C1-6 alkyl, or a substituted or unsubstituted C1-6 heteroalkyl; R 3a is a C 1-6 alkyl or a deuterated C 1-6 alkyl; R 4a is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted C 3-6 cycloalkyl, or a substituted or unsubstituted ternary to eighth-membered heterocyclyl; R5 is hydrogen, -NR O1 R O2 , -C(R O5 )R O3 R O4 , -C 1-4 alkyl-NR O1 R O2 , -C 1-4 alkyl-C(R O5 )R O3 R O4 , -C 1-4 alkyl-C(=O)-NR O1 R O2 , -C 1-4 alkyl-C(=O)-C(R O5 )R O3 R O4 , -C 1-4 alkyl-C(=O)-C 1-4 alkyl-NR O1 R O2 , -C 1-4 alkyl-C(=O)-C 1-4 alkyl-C(R O5 )R O3 R O4 , -C 1-4 alkyl-N(R O6 )C(=O)-NR O1 R O2 , -C 1-4 alkyl-N(R 06 )C(=O)-C(R 05 )R 03 R 04 , -C 1-4 alkyl-N(R 06 )C(=O)-C 1-4 alkyl-NR 01 R 02 , -C 1-4 alkyl-N(R 06 )C(=O)-C 1-4 alkyl-C(R 05 )R 03 R 04 , -OC 1-4 alkyl-NR 01 R 02 , -OC 1-4 alkyl-C(R 05 )R 03 R 04 , -OC 1-4 alkyl-N(R 06 )C(=O)-R 03 , -OC(R 05 )R 03 R 04 , -C 1-4 alkyl-NR 01 R 02 , -C 1-4 Alkyl-C(R O5 )R O3 R O4 , -N(R O6 )C(=O)-NR O1 R O2 , -N(R O6 )C(=O)-C(R O5 )R O3 R O4 , -C 2-4 Alkynyl-NR O1 R O2 , -C 2-4 Alkynyl-C(=O)-NR O1 R O2 , -C 2-4 Alkynyl-C(R O5 )R O3 R O4 , -C 1-4 Alkyl-C 2-4 Alkynyl-NR O1 R O2 , -C 1-4 Alkyl-C 2-4 Alkynyl-C(R O5 )R O3 R O4 , -C 2-4 Alkynyl-C 1-4 Alkyl-NR O1 R O2 , -C 2-4 alkynyl-C 1-4 alkyl-C(R O5 )R O3 R O4 , -C 1-4 alkyl-C 2-4 alkynyl-C 1-4 alkyl-NR O1 R O2 , -CH=CR O1 R O2 , -C 2-4 alkenyl-NR O1 R O2 , -C 2-4 alkenyl-C(R O5 )R O3 R O4 , -C 1-4 alkyl-C 2-4 alkenyl-NR O1 R O2 , -C 1-4 alkyl-C 2-4 alkenyl-C(R O5 )R O3 R O4 , -C 2-4 alkenyl-C 1-4 alkyl-NR O1 R O2 , -C 2-4 alkenyl-C 1-4 Alkyl-C(R O5 )R O3 R O4 , -C 1-4 alkyl-C 2-4 alkenyl-C 1-4 alkyl-NR O1 R O2 , -C=CR O3 R O4 , -OC 1-4 alkyl-substituted or unsubstituted 3 to 8-membered monocyclic heterocyclyl, -OC 1-4 alkyl-substituted or unsubstituted 5 to 15-membered tricyclic heterocyclyl, -OC 1-4 alkyl-substituted or unsubstituted 7 to 12-membered bicyclic heterocyclyl, -O-substituted or unsubstituted 3 to 8-membered monocyclic heterocyclyl, -O-substituted or unsubstituted 5 to 15-membered tricyclic heterocyclyl, -O-substituted or unsubstituted 7 to 12-membered bicyclic Heterocyclyl, -N=S(=O)(R O6 )(-C 1-4 alkyl-NR O1 R O2 ), -N(R O6 )-S(=O)(-C 1-4 alkyl-NR O1 R O2 ), -S(=O)(R O6 )(=NR O6 ), -S(=O)(-C 1-4 alkyl-NR O1 R O2 )(=NR O6 ), -S(=O) 2 (-C 1-4 alkyl-NR O1 R O2 ), -S(=O)(-C 1-4 alkyl-NR O1 R O2 ), -S(=O) 2 (-C 1-4 alkyl-C(R O5 )R O3 R O4 ), -S(=O)(-C 1-4 alkyl-C(R O5 )R 03 R 04 ), -C 2-4 alkynyl-substituted or unsubstituted 5- or 6-membered monocyclic heteroaryl, -C 2-4 alkynyl-substituted or unsubstituted 8- to 10-membered bicyclic heteroaryl, -C 2-4 alkynyl-substituted or unsubstituted 6- to 12-membered heteroaryl-fused heterocyclil, substituted or unsubstituted C 6-10 aryl, substituted or unsubstituted 5- or 6-membered monocyclic heteroaryl, substituted or unsubstituted 8- to 10-membered bicyclic heteroaryl, substituted or unsubstituted C 6-10 aryl-substituted or unsubstituted 3- to 8-membered monocyclic heterocyclil, substituted or unsubstituted 5- or 6-membered monocyclic heteroaryl-substituted or unsubstituted 3- to 8-membered Monocyclic heterocyclyl, substituted or unsubstituted C6-10 aryl- C1-4 alkyl-substituted or unsubstituted ternary to octary monocyclic heterocyclyl, substituted or unsubstituted pentary or six-membered monocyclic heteroaryl- C1-4 alkyl-substituted or unsubstituted ternary to octary monocyclic heterocyclyl, substituted or unsubstituted C6-10 aryl-fused substituted or unsubstituted ternary to octary monocyclic heterocyclyl, substituted or unsubstituted pentary or six-membered monocyclic heteroaryl-fused substituted or unsubstituted ternary to octary monocyclic heterocyclyl, substituted or unsubstituted C6-10 aryl- C1-4 alkyl-NR O1 R O2 , substituted or unsubstituted pentary or six-membered monocyclic heteroaryl-C 1-4 alkyl-NR O1 R O2 and; R O1 and R O2 are each independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 2-6 alkenyl, or substituted or unsubstituted C 2-6 alkynyl; or, R O1 and R O2 together with connected nitrogen atoms jointly form substituted or unsubstituted 5- to 15-membered tricyclic heterocyclils, substituted or unsubstituted 7- to 12-membered bicyclic heterocyclils, and substituted or unsubstituted 3- to 8-membered monocyclic heterocyclils; R O3 and R O4 are each independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 2-6 alkenyl, and substituted or unsubstituted C 2-6 alkynyl; two hydrogen atoms on the same carbon atom of the C 1-6 alkyl or C 1-6 alkoxy are optionally simultaneously substituted by -(CH 2 ) j - to form a cycloalkyl, wherein j is 2, 3, 4, 5, or 6; or R O3 and R O4 together with connected carbon atoms jointly form substituted or unsubstituted 5- to 15-membered tricyclic heterocyclils, 7- to 12-membered bicyclic heterocyclils, substituted or unsubstituted 3- to 8-membered monocyclic heterocyclils, substituted or unsubstituted 5- or 6-membered monocyclic heteroaryls, or substituted or unsubstituted 8- to 10-membered bicyclic heteroaryls; R O5 is hydrogen, deuterium, halogen, deuteride C 1-6 alkyl or C 1-6 alkyl; R O6 is hydrogen, deuterium, or C 1-6 alkyl; Y3 is -C(=O) R6 , -C(=S) R6 , -S(=O)( R07 )(= NR08 ), -S(=O)(R07)( R08 ), -S(=O) 2 ( R07 )( R08 ), -P(=O)( R07 )( R08 ), -C(=O ) -C1-4 alkyl- NR6- S(=O)( R07 )(= NR08 ), -C(=O) -C1-4 alkyl-N=S(=O)( R07 )( R08 ) or R11 ; R12 is hydrogen, C1-6 alkyl or deuterated C1-6 alkyl; Or Y3 , R12 co-form a substituted or unsubstituted nitrogen-containing ternary to octary heterocyclyl with a nitrogen atom connected thereto; one ring atom of the nitrogen-containing ternary to octary heterocyclyl is a nitrogen atom and optionally one or more (e.g., 1, 2, or 3) ring atoms are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; R6 is a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C1-6 heteroalkyl, a substituted or unsubstituted C3-6 cycloalkyl, a substituted or unsubstituted ternary to octary heterocyclyl, a substituted or unsubstituted C6-10 aryl, a substituted or unsubstituted pentary or 6-membered monocyclic heteroaryl, or a substituted or unsubstituted octary to 10-membered bicyclic heteroaryl; R 11 is a substituted or unsubstituted 3 to 10-membered heterocyclyl, a substituted or unsubstituted 5 or 6-membered monocyclic heteroaryl, a substituted or unsubstituted 8 to 10-membered bicyclic heteroaryl, a substituted or unsubstituted 6 to 12-membered heteroaryl-fused cycloalkyl, a substituted or unsubstituted 6 to 12-membered heteroaryl-fused heterocyclyl, a substituted or unsubstituted 7 to 12-membered bicyclic heterocyclyl, or a substituted or unsubstituted 5 to 15-membered tricyclic heterocyclyl; R O7 is hydrogen, deuterium, a substituted or unsubstituted C 1-6 alkyl, or a substituted or unsubstituted C 3-6 cycloalkyl; said substitution refers to being substituted by one or more groups (e.g., 1, 2, 3, or 4) selected from the group consisting of deuterium, C 1-6 alkyl, C 1-6 heteroalkyl, and pentagonal or hexagonal monocyclic heteroaryls; R O8 is hydrogen, deuterium, a substituted or unsubstituted C 1-6 alkyl or a substituted or unsubstituted C 3-6 cycloalkyl; said substitution refers to being substituted by one or more groups (e.g., 1, 2, 3, or 4) selected from the group consisting of deuterium, C 1-6 alkyl, C 1-6 heteroalkyl, and pentagonal or hexagonal monocyclic heteroaryls; R O9 is hydrogen, deuterium, halogen, or a substituted or unsubstituted C 1-6 alkyl; said substitution refers to being substituted by one or more groups (e.g., 1, 2, 3, or 4) selected from the group consisting of deuterium and halogen; R 10 is hydrogen, deuterium, halogen, or a substituted or unsubstituted C 1-6 alkyl; said substitution refers to being substituted by one or more groups (e.g., 1, 2, 3, or 4) selected from the group consisting of deuterium and halogen; Y 5 is O or S and; Y 4 is O or S and; R3 is hydrogen, a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C1-6 heteroalkyl, a substituted or unsubstituted C2-6 alkenyl, a substituted or unsubstituted C2-6 alkynyl, a substituted or unsubstituted C3-6 cycloalkyl, a substituted or unsubstituted ternary to octary heterocyclyl, a substituted or unsubstituted C6-10 aryl, a substituted or unsubstituted pentary or six-membered monocyclic heteroaryl, or a substituted or unsubstituted octary to ten-membered bicyclic heteroaryl; R 13 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl, or a substituted or unsubstituted C 1-6 alkoxy; R 14 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; or In W 4 and W 5 , R 13 and R 14 co-form a substituted or unsubstituted C 3-6 cycloalkyl, a substituted or unsubstituted C 6-10 aryl, a substituted or unsubstituted 5- or 6-membered monocyclic heteroaryl, or a substituted or unsubstituted 3- to 8-membered heterocyclic, together with the connected carbon atom; or In W 5 , R 14 and R 3 together form a substituted or unsubstituted nitrogen-containing quaternary to octanine monocyclic heterocyclyl with a connected atom; one ring atom of the nitrogen-containing quaternary to octanine monocyclic heterocyclyl is a nitrogen atom and optionally one or more (e.g., 1, 2, or 3) ring atoms are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; or In W6 , R13 and R3 together with the connected atoms jointly form a substituted or unsubstituted nitrogen-containing ternary to octary monocyclic heterocyclyl or a substituted or unsubstituted pentary or hexacyclic heteroaryl; one ring atom of the nitrogen-containing ternary to octary monocyclic heterocyclyl is a nitrogen atom, and optionally one or more (e.g., 1, 2, or 3) ring atoms are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; In each of the aforementioned groups, the substitution indicates that each of the aforementioned groups is independently substituted by 1, 2, 3, 4, 5, or 6 groups selected from group S1; The groups of the above S1 group are each independently -SF5 , deuterium, oxo (=O), thio (=S), =CR e R f , =NR e , halogen, cyano, hydroxy, carboxyl, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-20 cycloalkyl, ternary to 20-membered heterocyclyl, C6-14 aryl, 5-membered or 6-membered monocyclic heteroaryl, 8-membered to 10-membered bicyclic heteroaryl, -OC3-20 cycloalkyl, -O-ternary to 20-membered heterocyclyl, -OC6-14 aryl, -O-5-membered or 6-membered monocyclic heteroaryl, -O-8-membered to 10-membered bicyclic heteroaryl, -C≡CC 3-20 cycloalkyl, -C≡C-3 to 20-membered heterocyclyl, -C≡CC- 6-14 aryl, -C≡C-5 or 6-membered monocyclic heteroaryl, -C≡C-8 to 10-membered bicyclic heteroaryl, -C≡CC -1-4 alkyl-C 3-20 cycloalkyl, -C≡CC -1-4 alkyl-3 to 20-membered heterocyclyl, -C≡CC -1-4 alkyl-C 6-14 aryl, -C≡CC- 1-4 alkyl-5 or 6-membered monocyclic heteroaryl, -C≡CC -1-4 alkyl-8 to 10-membered bicyclic heteroaryl, -C 1-4 alkyl-hydroxy, -C 1-4 alkyl-cyano, -C 1-4 alkyl-C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-C 3-20 cycloalkyl, -C 1-4 alkyl-OC 3-20 cycloalkyl, -C 1-4 alkyl-3 to 20 heterocyclyl, -C 1-4 alkyl-O-3 to 20 heterocyclyl, -C 1-4 alkyl-C 6-14 aryl, -C 1-4 alkyl-OC 6-14 aryl, -C 1-4 alkyl-5 or 6 monocyclic heteroaryl, -C 1-4 alkyl-O-5 or 6 monocyclic heteroaryl, -C 1-4 alkyl-8 to 10 bicyclic heteroaryl, -C 1-4 alkyl-O-8 to 10-membered bicyclic heteroaryl, -OC 1-4 alkyl-hydroxy, -OC 1-4 alkyl-cyano, -OC 1-4 alkyl-C 1-6 alkyl, -OC 1-4 alkyl-C 1-6 alkoxy, -OC 1-4 alkyl-C 3-20 cycloalkyl, -OC 1-4 alkyl-OC 3-20 cycloalkyl, -OC 1-4 alkyl-3 to 20-membered heterocyclyl, -OC 1-4 alkyl-O-3 to 20-membered heterocyclyl, -OC 1-4 alkyl-C 6-14 aryl, -OC 1-4 alkyl-OC 6-14 aryl, -OC 1-4 alkyl-5-membered or 6-membered monocyclic heteroaryl, -OC 1-4 alkyl-O-5-membered or 6-membered monocyclic heteroaryl, -OC 1-4 alkyl-8 to 10 bicyclic heteroaryl, -OC 1-4 alkyl-O-8 to 10 bicyclic heteroaryl, -S(=O) 2 -C 1-6 alkyl, -S(=O) 2 -C 3-20 cycloalkyl, -S(=O) 2 -3 to 20 heterocyclic, -C(=O)OC 1-6 alkyl, -C(=O)OC 3-20 cycloalkyl, -C(=O)-C 1-6 alkyl, -C(=O)-C 3-20 cycloalkyl, -C(=O)-C 6-14 aryl, -NR a1 R b1 , -C(=O)-NR a1 R b1 , -C(=O)-NR d1 -C 1-4 alkyl-R c1 , -OR c1 , -C 1-4 alkyl-S(=O) 2 -C 1-6 alkyl, -C 1-4 alkyl-S(=O) 2 -C 3-20 cycloalkyl, -C 1-4 alkyl-S(=O) 2 -3 to 20 heterocyclic, -C 1-4 alkyl-C(=O)OC 1-6 alkyl, -C 1-4 alkyl-C(=O)OC 3-20 cycloalkyl, -C 1-4 alkyl-C(=O)-C 1-6 alkyl, -C 1-4 alkyl-C(=O)-C 3-20 cycloalkyl, -C 1-4 alkyl-C(=O)-C 6-14 aryl, -C(=O)-5 or 6 monocyclic heteroaryl, -C(=O)-8 to 10 bicyclic heteroaryl, -C(=O)-C 1-6 alkyl-C 3-20 cycloalkyl, -C(=O)-C 1-6 alkyl-3 to 20 heterocyclic, -C(=O)-C 1-6 alkyl-C 6-14 aryl, -C(=O)-C 1-6 alkyl-5 or 6 monocyclic heteroaryl, -C(=O)-C 1-6 alkyl-8 to 10 bicyclic heteroaryl, -C 1-4 alkyl-NR a1 R b1 , -C 1-4 alkyl-C(=O)-NR a1 R b1 , -C≡CC(=O)-NR a1 R b1 , -C≡CC 1-4 alkyl-C(=O)-NR a1 R b1 , -C 1-4 alkyl-OR c1 , -C 1-4 Alkyl-P(=O)-( C1-6 alkyl) 2 , -P(=O)-( C1-6 alkyl) 2 , -C1-4 alkyl-NR d1 -C(=O)-R c1 , -C1-4 alkyl-NR d1 -C(=O)-NR a1 R b1 , -C1-4 alkyl-NR d1 -S(=O) 2 -R c1 , -C1-4 alkyl-S(=O) 2 -NR a1 R b1 , -C1-4 alkyl-NR d1 -S(=O) 2 -NR a1 R b1 , -NR d1 -C(=O)-R c1 , -NR d1 -C(=O) -C1-4 alkyl-R c1 , -NR d1 -C(=O)-NR a1 R b1 , -NR d1 Selected from the group consisting of -S(=O) 2 -R c1 , -S(=O) 2 -NR a1 R b1 , -NR d1 -S(=O) 2 -NR a1 R b1 , and -P(=O)-(C 1-6 alkyl) 2 ; wherein the C 1-6 alkyl, the C 1-6 alkoxy, the C 2-6 alkenyl, and the C 2-6 alkynyl are each independently optionally substituted by one, two, or three groups selected from halogen, deuterium, cyano, or hydroxy; The C 3-20 cycloalkyl, the 3 to 20-membered heterocyclyl, the C 6-14 aryl, the 5-membered or 6-membered monocyclic heteroaryl, and the 8-membered to 10-membered bicyclic heteroaryl are each independently selectively substituted by 1, 2, 3, or 4 groups selected from group S2; In each of the groups described above, each R a1 and R b1 is independently H, C 1-6 alkyl, C 1-6 alkyl halide, C 1-6 alkyl deuteride, -C 1-4 alkyl-hydroxy, -C 1-4 alkyl-cyano, -C 1-4 alkyl-C 1-6 alkyl halide, -C 1-4 alkyl-deuteride C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-C 1-6 alkoxy halide, -C 1-4 alkyl-deuteride C 1-6 alkoxy, C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-OC 3-6 monocyclic cycloalkyl, ternary to six-membered Monocyclic heterocyclyl, -C 1-4 alkyl-ternary to 6-membered monocyclic heterocyclyl, -C 1-4 alkyl-O-ternary to 6-membered monocyclic heterocyclyl, phenyl, -C 1-4 alkyl-phenyl, 5-membered or 6-membered monocyclic heteroaryl, -C 1-4 alkyl-5-membered or 6-membered monocyclic heteroaryl, 8-membered to 10-membered bicyclic heteroaryl, -C 1-4 alkyl-8-membered to 10-membered bicyclic heteroaryl, -S (=O) 2 -C 1-6 alkyl, -S(=O) 2 -C 3-6 monocyclic cycloalkyl, -S(=O) 2 -ternary to 6-membered monocyclic heterocyclyl, -C 1-4 alkyl-S(=O) 2 -C 1-6 alkyl, -C 1-4 alkyl-S(=O) 2 -C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-S(=O) 2 -3 to 6-membered monocyclic heterocyclyl, -C(=O)-C 1-6 alkyl, -C(=O)-C 3-6 monocyclic cycloalkyl, -C(=O)-3 to 6-membered monocyclic heterocyclyl; The C3-6 monocyclic cycloalkyl, the 3- to 6-membered monocyclic heterocyclyl, the phenyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are optionally selected from one or two groups consisting of halogen, hydroxy, carboxyl, nitro, C1-6 alkyl, C1-6 alkyl halides, C1-6 alkyl deuterides, C1-6 alkoxy, C1-6 alkoxy halides, C1-6 alkoxy deuterides, -NH2 , -NHC1-6 alkyl, -N( C1-6 alkyl) 2 , -C1-4 alkyl-P(=O)-( C1-6 alkyl) 2 , and -P(=O)-( C1-6 alkyl) 2 . Replaced by; or Each R a1 and R b1 co-forms a ternary to 20-membered heterocyclyl together with a nitrogen atom connected thereto; said ternary to 20-membered heterocyclyls are each independently optionally substituted by one or two groups selected from the group consisting of halogen, hydroxy, carboxyl, nitro, C 1-6 alkyl, C 1-6 alkyl halogenated, C 1-6 alkyl deuteride , C 1-6 alkoxy, C 1-6 alkoxy halogenated, C 1-6 alkoxy deuteride, -NH 2 , -NHC 1-6 alkyl, -N(C 1-6 alkyl) 2 , -C 1-4 alkyl-P(=O)-(C 1-6 alkyl) 2 and -P(=O)-( C 1-6 alkyl) 2 ; In each of the aforementioned groups, each R d1 is independently H, C 1-6 alkyl or deuterated C 1-6 alkyl; In each of the groups described above, each R c1 is independently H, C 1-6 alkyl, -C 1-4 alkyl-hydroxy, -C 1-4 alkyl-NR a1 R b1 , halogenated C 1-6 alkyl, deuteriumated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, deuteriumated C 1-6 alkoxy, -C 1-4 alkyl-halogenated C 1-6 alkyl, -C 1-4 alkyl-deuteriumated C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-halogenated C 1-6 alkoxy, -C 1-4 alkyl-deuteriumated C 1-6 alkoxy, C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-C 3-6 Monocyclic cycloalkyl, -C 1-4 alkyl-OC 3-6 monocyclic cycloalkyl, 3 to 6-membered monocyclic heterocyclyl, -C 1-4 alkyl-3 to 6-membered monocyclic heterocyclyl, -C 1-4 alkyl-O-3 to 6-membered monocyclic heterocyclyl, phenyl, -C 1-4 alkyl-phenyl, 5 or 6-membered monocyclic heteroaryl, -C 1-4 alkyl-5 or 6-membered monocyclic heteroaryl, 8 to 10-membered bicyclic heteroaryl or -C 1-4 alkyl-8 to 10-membered bicyclic heteroaryl; The C3-6 monocyclic cycloalkyl, the 3 to 6-membered monocyclic heterocyclyl, the phenyl, the 5 or 6-membered monocyclic heteroaryl, and the 8 to 10-membered bicyclic heteroaryl are composed of halogen, hydroxy, carboxyl, nitro, C1-6 alkyl, C3-6 monocyclic cycloalkyl, C1-6 alkyl halides, C1-6 alkyl deuterides, C1-6 alkoxy, C1-6 alkoxy halides, C1-6 alkoxy deuterides, -NH2, -NHC1-6 alkyl, -N( C1-6 alkyl ) 2 , -C1-4 alkyl-P(=O)-( C1-6 alkyl )2 , and -P(=O)-( C1-6 alkyl) 2 . Optionally substituted by one or two groups selected from the group; In each of the groups described above, each group of the S2 group is independently deuterium, oxo (=O), thio (=S), =CR e R f , =NR e , halogen, hydroxy, carboxyl, nitro, C 1-6 alkyl, C 1-6 alkyl halide, C 1-6 alkyl deuterium, C 1-6 alkoxy, C 1-6 alkoxy halide, C 1-6 alkoxy deuterium, -NH 2 , -NHC 1-6 alkyl, -N(C 1-6 alkyl) 2 , -(C=O)-NHC 1-6 alkyl, -(C=O)-N(C 1-6 alkyl) 2 , -C 1-4 alkyl-P(=O)-(C 1-6 alkyl) 2 , -P(=O)-(C 1-6 alkyl) 2 , Selected from the group consisting of -(C=O)C 1-6 alkyl, -SF 5 and -C 1-4 alkyl-hydroxy; In each of the groups described above, the -C 1-4 alkyl- is unsubstituted; or 1, 2, 3, or 4 hydrogen atoms on the -C 1-4 alkyl- are each independently substituted by a group selected from halogen, cyano, hydroxy, C 1-6 alkyl, halogenated C 1-6 alkyl, deuteriumated C 1-6 alkyl, -CH 2 -hydroxy, -CH 2 -cyano, phenyl, or C 3-6 monocyclic cycloalkyl; or two hydrogen atoms on the same carbon atom of the C 1-4 alkyl are simultaneously substituted by -(CH 2 ) j - to form a cycloalkyl, where j is 2, 3, 4, 5, or 6; or two hydrogen atoms on the same carbon atom of the C 1-4 alkyl are simultaneously substituted by =CR e R f ; In each of the aforementioned groups, R e is independently H, a halogen, a C1-6 alkyl, a C1-6 alkyl halide, or a C1-6 alkyl deuteride; In each of the aforementioned groups, R f is independently H, a halogen, a C1-6 alkyl, a C1-6 alkyl halide, or a C1-6 alkyl deuteride; In each of the groups described above, one or more (e.g., 1, 2, 3, or 4) ring atoms of the ternary to eighth heterocyclil, ternary to tenth heterocyclil, or ternary to eighth monocyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, or 4) ring atoms of the C 1-6 heteroalkyl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; and one or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the henary to twelveth cyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; One or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 3 to 20-membered heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, or 4) ring atoms of the above 5-membered or 6-membered monocyclic heteroaryl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 8 to 10-membered cyclic heteroaryl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; and one or more (e.g., 1, 2, 3, or 4) ring atoms of the above 3 to 6-membered monocyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; One or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 5- to 15-membered tricyclic heterocyclyl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 6- to 12-membered heteroaryl-fused cycloalkyl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; and one or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 6- to 12-membered heteroaryl-fused heterocyclyl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; Here, if the ring atom is a sulfur atom, the sulfur atom is optionally substituted by one or two groups selected from oxo and =NR e ; the definition of R e is the same as before; Here, where the ring atom is a phosphorus atom, the corresponding phosphorus atom is selectively substituted by one or two groups selected from oxo and =NR e ; the definition of R e is the same as above, a compound or its stable deuterated derivative or its stereoisomer, or its pharmaceutically acceptable salt, solvate or prodrug.
  2. In paragraph 1, here, Is , , , , , and It is selected from a group consisting of; where, the definition of X is the same as before; R3 is a compound or a stable deuterated derivative thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, which is hydrogen, a substituted or unsubstituted C1-6 alkyl , a substituted or unsubstituted C1-6 heteroalkyl, a substituted or unsubstituted C2-6 alkenyl, a substituted or unsubstituted C2-6 alkynyl, a substituted or unsubstituted C3-6 cycloalkyl, a substituted or unsubstituted ternary to octary, a substituted or unsubstituted C6-10 aryl, a substituted or unsubstituted pentary or six-membered monocyclic heteroaryl, or a substituted or unsubstituted octary to ten-membered cycloaryl.
  3. In paragraph 1, here, Is or Selected from; here, the definition of X is the same as before; R3 is hydrogen, a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C1-6 heteroalkyl, a substituted or unsubstituted C2-6 alkenyl, a substituted or unsubstituted C2-6 alkynyl, a substituted or unsubstituted C3-6 cycloalkyl, a substituted or unsubstituted ternary to octary heterocyclyl, a substituted or unsubstituted C6-10 aryl, a substituted or unsubstituted pentary or 6aryl monocyclic heteroaryl, or a substituted or unsubstituted octary to 10aryl bicyclic heteroaryl; and R13 is hydrogen, a halogen, a substituted or unsubstituted C1-6 alkoxy, or a substituted or unsubstituted C1-6 alkyl; or, R 13 and R 3 together with the connected atoms to form a substituted or unsubstituted nitrogen-containing ternary to octary monocyclic heterocyclyl or a substituted or unsubstituted quinary or hexacyclic heteroaryl; a compound or a stable deuterated derivative thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein one ring atom of the nitrogen-containing ternary to octary monocyclic heterocyclyl is a nitrogen atom and optionally one or more (e.g., 1, 2, or 3) ring atoms are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus.
  4. In claim 1, the compound of formula (I) is as represented by formula (A1), formula (A2), formula (A3), formula (A4), formula (A5), formula (A6), formula (B1), formula (B2), formula (B3) or formula (B4): (A1) (A2) (A3) (A4) (A5) (A6) (B1) (B2) (B3) (B4) In the equation, R3 is hydrogen, a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C1-6 heteroalkyl, a substituted or unsubstituted C2-6 alkenyl, a substituted or unsubstituted C2-6 alkynyl, a substituted or unsubstituted C3-6 cycloalkyl, a substituted or unsubstituted ternary to octary heterocyclyl, a substituted or unsubstituted C6-10 aryl, a substituted or unsubstituted pentary or six-membered monocyclic heteroaryl, or a substituted or unsubstituted octary to ten-membered bicyclic heteroaryl; R 13 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl or a substituted or unsubstituted C 1-6 alkoxy; or R 13 and R 3 together with connected atoms jointly form a substituted or unsubstituted nitrogen-containing ternary to octary monocyclic heterocyclyl; R 42 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; R 43 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; or R 42 and R 43 together form a substituted or unsubstituted C 3-6 cycloalkyl or a substituted or unsubstituted ternary to octary heterocyclyl with a connected carbon atom; L1 is -N( R00 )C(=O)-, -N( R00 )C(=O)-O-, -C1-4 alkyl-N( R00 )C(=O)-, -C(=O)N( R00 ) -C1-4 alkyl-, -C1-4 alkyl-N( R00 )C(=S)-, substituted or unsubstituted C1-6 alkyl, -substituted or unsubstituted C1-6 alkyl-O-, -substituted or unsubstituted C2-6 alkenyl-O-, substituted or unsubstituted C3-6 cycloalkyl, substituted or unsubstituted ternary to octary heterocyclyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted pentary or sixary monocyclic heteroaryl, substituted or unsubstituted octary to tenary bicyclic Heteroaryl, -L2 -substituted or unsubstituted C6-10 aryl, -L2 -substituted or unsubstituted 5- or 6-membered monocyclic heteroaryl, or -L2 -substituted or unsubstituted 3- to 8-membered heterocyclicl; L2 is -O-, -C 1-4 alkyl-, -N(R 00 )-, -C(=O)-, -CR 09 =CR 10 -, -N(R 00 )C(=O)- or -N(R 00 )C(=S)- and; R 00 is hydrogen or C 1-6 alkyl; R1 is hydrogen, deuterium, halogen, hydroxy, C1-6 alkyl, or a substituted or unsubstituted C1-6 heteroalkyl; R2 is hydrogen, deuterium, halogen, C1-6 alkyl, or a substituted or unsubstituted C1-6 heteroalkyl; R 4a is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted C 3-6 cycloalkyl, or a substituted or unsubstituted ternary to octary heterocyclyl; R5 is -NR O1 R O2 or -C 2-4 alkynyl-C 1-4 alkyl-NR O1 R O2 ; R O1 and R O2 are each independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 2-6 alkenyl, or substituted or unsubstituted C 2-6 alkynyl; or, R O1 and R O2 together with connected nitrogen atoms jointly form substituted or unsubstituted 5- to 15-membered tricyclic heterocyclils, substituted or unsubstituted 7- to 12-membered bicyclic heterocyclils, and substituted or unsubstituted 3- to 8-membered monocyclic heterocyclils; R O9 is hydrogen, deuterium, halogen, or a substituted or unsubstituted C 1-6 alkyl; said substitution refers to being substituted by one or more groups (e.g., 1, 2, 3, or 4) selected from the group consisting of deuterium and halogen; R 10 is hydrogen, deuterium, halogen, or a substituted or unsubstituted C 1-6 alkyl; said substitution refers to being substituted by one or more groups (e.g., 1, 2, 3, or 4) selected from the group consisting of deuterium and halogen; R6 is a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C1-6 heteroalkyl, a substituted or unsubstituted C3-6 cycloalkyl, a substituted or unsubstituted ternary to octary heterocyclyl, a substituted or unsubstituted C6-10 aryl, a substituted or unsubstituted pentary or 6-membered monocyclic heteroaryl, or a substituted or unsubstituted octary to 10-membered bicyclic heteroaryl; In each of the aforementioned groups, the substitution indicates that each of the aforementioned groups is independently substituted by 1, 2, 3, 4, 5, or 6 groups selected from group S1; The groups of the above S1 group are each independently -SF5 , deuterium, oxo (=O), thio (=S), =CR e R f , =NR e , halogen, cyano, hydroxy, carboxyl, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-20 cycloalkyl, ternary to 20-membered heterocyclyl, C6-14 aryl, 5-membered or 6-membered monocyclic heteroaryl, 8-membered to 10-membered bicyclic heteroaryl, -OC3-20 cycloalkyl, -O-ternary to 20-membered heterocyclyl, -OC6-14 aryl, -O-5-membered or 6-membered monocyclic heteroaryl, -O-8-membered to 10-membered bicyclic heteroaryl, -C≡CC 3-20 cycloalkyl, -C≡C-3 to 20-membered heterocyclyl, -C≡CC- 6-14 aryl, -C≡C-5 or 6-membered monocyclic heteroaryl, -C≡C-8 to 10-membered bicyclic heteroaryl, -C≡CC -1-4 alkyl-C 3-20 cycloalkyl, -C≡CC -1-4 alkyl-3 to 20-membered heterocyclyl, -C≡CC -1-4 alkyl-C 6-14 aryl, -C≡CC- 1-4 alkyl-5 or 6-membered monocyclic heteroaryl, -C≡CC -1-4 alkyl-8 to 10-membered bicyclic heteroaryl, -C 1-4 alkyl-hydroxy, -C 1-4 alkyl-cyano, -C 1-4 alkyl-C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-C 3-20 cycloalkyl, -C 1-4 alkyl-OC 3-20 cycloalkyl, -C 1-4 alkyl-3 to 20 heterocyclyl, -C 1-4 alkyl-O-3 to 20 heterocyclyl, -C 1-4 alkyl-C 6-14 aryl, -C 1-4 alkyl-OC 6-14 aryl, -C 1-4 alkyl-5 or 6 monocyclic heteroaryl, -C 1-4 alkyl-O-5 or 6 monocyclic heteroaryl, -C 1-4 alkyl-8 to 10 bicyclic heteroaryl, -C 1-4 alkyl-O-8 to 10-membered bicyclic heteroaryl, -OC 1-4 alkyl-hydroxy, -OC 1-4 alkyl-cyano, -OC 1-4 alkyl-C 1-6 alkyl, -OC 1-4 alkyl-C 1-6 alkoxy, -OC 1-4 alkyl-C 3-20 cycloalkyl, -OC 1-4 alkyl-OC 3-20 cycloalkyl, -OC 1-4 alkyl-3 to 20-membered heterocyclyl, -OC 1-4 alkyl-O-3 to 20-membered heterocyclyl, -OC 1-4 alkyl-C 6-14 aryl, -OC 1-4 alkyl-OC 6-14 aryl, -OC 1-4 alkyl-5-membered or 6-membered monocyclic heteroaryl, -OC 1-4 alkyl-O-5-membered or 6-membered monocyclic heteroaryl, -O -C 1-4 alkyl-8 to 10 bicyclic heteroaryl, -O -C 1-4 alkyl-O-8 to 10 bicyclic heteroaryl, -S(=O) 2 -C 1-6 alkyl, -S(=O) 2 -C 3-20 cycloalkyl, -S(=O) 2 -3 to 20 heterocyclic, -C(=O)OC 1-6 alkyl, -C(=O)OC 3-20 cycloalkyl, -C(=O)-C 1-6 alkyl, -C(=O)-C 3-20 cycloalkyl, -C(=O)-C 6-14 aryl, -NR a1 R b1 , -C(=O)-NR a1 R b1 , -C(=O)-NR d1 -C 1-4 alkyl-R c1 , -OR c1 , -C 1-4 alkyl-S(=O) 2 -C 1-6 alkyl, -C 1-4 alkyl-S(=O) 2 -C 3-20 cycloalkyl, -C 1-4 alkyl-S(=O) 2 -3 to 20 heterocyclic, -C 1-4 alkyl-C(=O)OC 1-6 alkyl, -C 1-4 alkyl-C(=O)OC 3-20 cycloalkyl, -C 1-4 alkyl-C(=O)-C 1-6 alkyl , -C 1-4 alkyl-C(=O)-C 3-20 cycloalkyl, -C 1-4 alkyl-C(=O)-C 6-14 aryl, -C(=O)-5 or 6 monocyclic heteroaryl, -C(=O)-8 to 10 bicyclic Heteroaryl, -C(=O)-C 1-6 alkyl-C 3-20 cycloalkyl, -C(=O)-C 1-6 alkyl-3 to 20-membered heterocyclyl, -C(=O)-C 1-6 alkyl-C 6-14 aryl, -C(=O)-C 1-6 alkyl-5-membered or 6-membered monocyclic heteroaryl, -C(=O)-C 1-6 alkyl-8 to 10-membered bicyclic heteroaryl, -C 1-4 alkyl-NR a1 R b1 , -C 1-4 alkyl-C(=O)-NR a1 R b1 , -C≡CC(=O)-NR a1 R b1 , -C≡CC 1-4 alkyl-C(=O)-NR a1 R b1 , -C 1-4 alkyl-OR c1 , -C 1-4 alkyl-P(=O)-(C 1-6 alkyl) 2 , -P(=O)-(C 1-6 alkyl) 2 , -C 1-4 alkyl-NR d1 -C(=O)-R c1 , -C 1-4 alkyl-NR d1 -C(=O)-NR a1 R b1 , -C 1-4 alkyl-NR d1 -S(=O) 2 -R c1 , -C 1-4 alkyl-S(=O) 2 -NR a1 R b1 , -C 1-4 alkyl-NR d1 -S(=O) 2 -NR a1 R b1 , -NR d1 -C(=O)-R c1 , -NR d1 -C(=O)-C 1-4 alkyl-R c1 , -NR d1 -C(=O)-NR a1 R b1 , Selected from the group consisting of -NR d1 -S(=O) 2 -R c1 , -S(=O) 2 -NR a1 R b1 , -NR d1 -S(=O) 2 -NR a1 R b1 and -P(=O)-(C 1-6 alkyl) 2 ; wherein the C 1-6 alkyl, the C 1-6 alkoxy, the C 2-6 alkenyl, and the C 2-6 alkynyl are each independently optionally substituted by one, two, or three groups selected from halogen, deuterium, cyano, or hydroxy; The C 3-20 cycloalkyl, the 3 to 20-membered heterocyclyl, the C 6-14 aryl, the 5-membered or 6-membered monocyclic heteroaryl, and the 8-membered to 10-membered bicyclic heteroaryl are each independently selectively substituted by 1, 2, 3, or 4 groups selected from group S2; In each of the groups described above, each R a1 and R b1 is independently H, C 1-6 alkyl, C 1-6 alkyl halide, C 1-6 alkyl deuteride, -C 1-4 alkyl-hydroxy, -C 1-4 alkyl-cyano, -C 1-4 alkyl-C 1-6 alkyl halide, -C 1-4 alkyl-deuteride C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-C 1-6 alkoxy halide, -C 1-4 alkyl-deuteride C 1-6 alkoxy, C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-OC 3-6 monocyclic cycloalkyl, ternary to six-membered Monocyclic heterocyclyl, -C 1-4 alkyl-ternary to 6-membered monocyclic heterocyclyl, -C 1-4 alkyl-O-ternary to 6-membered monocyclic heterocyclyl, phenyl, -C 1-4 alkyl-phenyl, 5-membered or 6-membered monocyclic heteroaryl, -C 1-4 alkyl-5-membered or 6-membered monocyclic heteroaryl, 8-membered to 10-membered bicyclic heteroaryl, -C 1-4 alkyl-8-membered to 10-membered bicyclic heteroaryl, -S (=O) 2 -C 1-6 alkyl, -S(=O) 2 -C 3-6 monocyclic cycloalkyl, -S(=O) 2 -ternary to 6-membered monocyclic heterocyclyl, -C 1-4 alkyl-S(=O) 2 -C 1-6 alkyl, -C 1-4 alkyl-S(=O) 2 -C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-S(=O) 2 -3 to 6-membered monocyclic heterocyclyl, -C(=O)-C 1-6 alkyl, -C(=O)-C 3-6 monocyclic cycloalkyl or -C(=O)-3 to 6-membered monocyclic heterocyclyl; The C3-6 monocyclic cycloalkyl, the 3- to 6-membered monocyclic heterocyclyl, the phenyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are optionally selected from one or two groups consisting of halogen, hydroxy, carboxyl, nitro, C1-6 alkyl, C1-6 alkyl halides, C1-6 alkyl deuterides, C1-6 alkoxy, C1-6 alkoxy halides, C1-6 alkoxy deuterides, -NH2 , -NHC1-6 alkyl, -N( C1-6 alkyl) 2 , -C1-4 alkyl-P(=O)-( C1-6 alkyl) 2 , and -P(=O)-( C1-6 alkyl) 2 . Replaced by; or Each R a1 and R b1 co-forms a ternary to 20-membered heterocyclyl together with a nitrogen atom connected thereto; said ternary to 20-membered heterocyclyls are each independently optionally substituted by one or two groups selected from the group consisting of halogen, hydroxy, carboxyl, nitro, C 1-6 alkyl, C 1-6 alkyl halogenated, C 1-6 alkyl deuteride , C 1-6 alkoxy, C 1-6 alkoxy halogenated, C 1-6 alkoxy deuteride, -NH 2 , -NHC 1-6 alkyl, -N(C 1-6 alkyl) 2 , -C 1-4 alkyl-P(=O)-(C 1-6 alkyl) 2 and -P(=O)-( C 1-6 alkyl) 2 ; In each of the aforementioned groups, each R d1 is independently H, C 1-6 alkyl or deuterated C 1-6 alkyl; In each of the groups described above, each R c1 is independently H, C 1-6 alkyl, C 1-6 alkyl halogenated, C 1-6 alkyl deuteriumated, C 1-6 alkoxy, C 1-6 alkoxy halogenated, C 1-6 alkoxy deuteriumated, -C 1-4 alkyl-C 1-6 alkyl halogenated, -C 1-4 alkyl-deuteriumated C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-C 1-6 alkoxy halogenated, -C 1-4 alkyl-deuteriumated C 1-6 alkoxy, C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl - C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-OC 3-6 monocyclic cycloalkyl, ternary to 6-membered monocyclic heterocyclyl, -C1-4 alkyl-3 to 6-membered monocyclic heterocyclyl, -C1-4 alkyl-O-3 to 6-membered monocyclic heterocyclyl, phenyl, -C1-4 alkyl-phenyl, 5-membered or 6-membered monocyclic heteroaryl, -C1-4 alkyl-5-membered or 6-membered monocyclic heteroaryl, 8 to 10-membered bicyclic heteroaryl or -C1-4 alkyl-8 to 10-membered bicyclic heteroaryl; The C3-6 monocyclic cycloalkyl, the 3 to 6-membered monocyclic heterocyclyl, the phenyl, the 5 or 6-membered monocyclic heteroaryl, and the 8 to 10-membered bicyclic heteroaryl are selected from one or two groups consisting of halogen, hydroxy, carboxyl, nitro, C1-6 alkyl, C1-6 alkyl halides, C1-6 alkyl deuterides, C1-6 alkoxy, C1-6 alkoxy halides, C1-6 alkoxy deuterides, -NH2 , -NHC1-6 alkyl, -N( C1-6 alkyl) 2 , -C1-4 alkyl-P(=O)-( C1-6 alkyl) 2 , and -P(=O)-( C1-6 alkyl) 2 Optionally substituted; In each of the groups described above, each group of the S2 group is independently deuterium, oxo (=O), thio (=S), =CR e R f , =NR e , halogen, hydroxy, carboxyl, nitro, C 1-6 alkyl, C 1-6 alkyl halide, C 1-6 alkyl deuterium, C 1-6 alkoxy, C 1-6 alkoxy halide, C 1-6 alkoxy deuterium, -NH 2 , -NHC 1-6 alkyl, -N(C 1-6 alkyl) 2 , -(C=O)-NHC 1-6 alkyl, -(C=O)-N(C 1-6 alkyl) 2 , -C 1-4 alkyl-P(=O)-(C 1-6 alkyl) 2 , -P(=O)-(C 1-6 alkyl) 2 , Selected from the group consisting of -(C=O)C 1-6 alkyl and -SF 5 ; In each of the groups described above, the -C 1-4 alkyl- is unsubstituted; or 1, 2, 3, or 4 hydrogen atoms on the -C 1-4 alkyl- are each independently substituted by a group selected from halogen, cyano, hydroxy, C 1-6 alkyl, halogenated C 1-6 alkyl, deuteriumated C 1-6 alkyl, -CH 2 -hydroxy, -CH 2 -cyano, or phenyl; or two hydrogen atoms on the same carbon atom of the C 1-4 alkyl are simultaneously substituted by -(CH 2 ) j - to form a cycloalkyl, where j is 2, 3, 4, 5, or 6; or two hydrogen atoms on the same carbon atom of the C 1-4 alkyl are simultaneously substituted by =CR e R f ; In each of the aforementioned groups, R e is independently H, a halogen, a C1-6 alkyl, a C1-6 alkyl halide, or a C1-6 alkyl deuteride; In each of the aforementioned groups, R f is independently H, a halogen, a C1-6 alkyl, a C1-6 alkyl halide, or a C1-6 alkyl deuteride; In each of the groups described above, one or more (e.g., 1, 2, 3, or 4) ring atoms of the ternary to eighth heterocyclil, ternary to tenth heterocyclil, or ternary to eighth monocyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, or 4) ring atoms of the C 1-6 heteroalkyl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; and one or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the henary to twelveth cyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; One or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 3 to 20-membered heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, or 4) ring atoms of the above 5-membered or 6-membered monocyclic heteroaryl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 8 to 10-membered cyclic heteroaryl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; and one or more (e.g., 1, 2, 3, or 4) ring atoms of the above 3 to 6-membered monocyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; One or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 5 to 15-membered tricyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; Here, if the ring atom is a sulfur atom, the sulfur atom is optionally substituted by one or two groups selected from oxo and =NR e ; the definition of R e is the same as before; Here, where the ring atom is a phosphorus atom, the corresponding phosphorus atom is selectively substituted by one or two groups selected from oxo and =NR e ; the definition of R e is the same as above, a compound or its stable deuterated derivative or its stereoisomer, or its pharmaceutically acceptable salt, solvate or prodrug.
  5. In claim 1, the compound of formula (I) is as represented by formula (C1): (C1) R 42 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; R 43 is hydrogen, a halogen, a substituted or unsubstituted C 1-6 alkyl; or R 42 and R 43 together form a substituted or unsubstituted C 3-6 cycloalkyl or a substituted or unsubstituted ternary to octary heterocyclyl with a connected carbon atom; L1 is -N( R00 )C(=O)-O-, -C1-4 alkyl-N( R00 )C(=O)-, -C(=O)N( R00 ) -C1-4 alkyl-, -C1-4 alkyl-N( R00 )C(=S)-, -substituted or unsubstituted C1-6 alkyl-O- or -substituted or unsubstituted C2-6 alkenyl-O-; R 00 is hydrogen or C 1-6 alkyl; R1 is hydrogen, deuterium, halogen, hydroxyl, C1-6 alkyl, or a substituted or unsubstituted C1-6 heteroalkyl; R2 is hydrogen, deuterium, halogen, C1-6 alkyl, or a substituted or unsubstituted C1-6 heteroalkyl; R3 is hydrogen, a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C1-6 heteroalkyl, a substituted or unsubstituted C2-6 alkenyl, a substituted or unsubstituted C2-6 alkynyl, a substituted or unsubstituted C3-6 cycloalkyl, a substituted or unsubstituted ternary to octary heterocyclyl, a substituted or unsubstituted C6-10 aryl, a substituted or unsubstituted pentary or six-membered monocyclic heteroaryl, or a substituted or unsubstituted octary to ten-membered bicyclic heteroaryl; R 4a is a substituted or unsubstituted C 1-6 alkyl, a substituted or unsubstituted C 3-6 cycloalkyl, or a substituted or unsubstituted ternary to eighth-membered heterocyclyl; R5 is -NR O1 R O2 or -C 2-4 alkynyl-C 1-4 alkyl-NR O1 R O2 ; R O1 and R O2 are each independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 alkoxy, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 2-6 alkenyl, or substituted or unsubstituted C 2-6 alkynyl; or, R O1 and R O2 together with connected nitrogen atoms jointly form substituted or unsubstituted 5- to 15-membered tricyclic heterocyclils, substituted or unsubstituted 7- to 12-membered bicyclic heterocyclils, and substituted or unsubstituted 3- to 8-membered monocyclic heterocyclils; R6 is a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C1-6 heteroalkyl, a substituted or unsubstituted C3-6 cycloalkyl, a substituted or unsubstituted ternary to octary heterocyclyl, a substituted or unsubstituted C6-10 aryl, a substituted or unsubstituted pentary or 6-membered monocyclic heteroaryl, or a substituted or unsubstituted octary to 10-membered bicyclic heteroaryl; In each of the aforementioned groups, the substitution indicates that each of the aforementioned groups is independently substituted by 1, 2, 3, 4, 5, or 6 groups selected from group S1; The groups of the above S1 group are each independently -SF5 , deuterium, oxo (=O), thio (=S), =CR e R f , =NR e , halogen, cyano, hydroxy, carboxyl, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-20 cycloalkyl, ternary to 20-membered heterocyclyl, C6-14 aryl, 5-membered or 6-membered monocyclic heteroaryl, 8-membered to 10-membered bicyclic heteroaryl, -OC3-20 cycloalkyl, -O-ternary to 20-membered heterocyclyl, -OC6-14 aryl, -O-5-membered or 6-membered monocyclic heteroaryl, -O-8-membered to 10-membered bicyclic heteroaryl, -C≡CC 3-20 cycloalkyl, -C≡C-3 to 20-membered heterocyclyl, -C≡CC- 6-14 aryl, -C≡C-5 or 6-membered monocyclic heteroaryl, -C≡C-8 to 10-membered bicyclic heteroaryl, -C≡CC -1-4 alkyl-C 3-20 cycloalkyl, -C≡CC -1-4 alkyl-3 to 20-membered heterocyclyl, -C≡CC -1-4 alkyl-C 6-14 aryl, -C≡CC- 1-4 alkyl-5 or 6-membered monocyclic heteroaryl, -C≡CC -1-4 alkyl-8 to 10-membered bicyclic heteroaryl, -C 1-4 alkyl-hydroxy, -C 1-4 alkyl-cyano, -C 1-4 alkyl-C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-C 3-20 cycloalkyl, -C 1-4 alkyl-OC 3-20 cycloalkyl, -C 1-4 alkyl-3 to 20 heterocyclyl, -C 1-4 alkyl-O-3 to 20 heterocyclyl, -C 1-4 alkyl-C 6-14 aryl, -C 1-4 alkyl-OC 6-14 aryl, -C 1-4 alkyl-5 or 6 monocyclic heteroaryl, -C 1-4 alkyl-O-5 or 6 monocyclic heteroaryl, -C 1-4 alkyl-8 to 10 bicyclic heteroaryl, -C 1-4 alkyl-O-8 to 10-membered bicyclic heteroaryl, -OC 1-4 alkyl-hydroxy, -OC 1-4 alkyl-cyano, -OC 1-4 alkyl-C 1-6 alkyl, -OC 1-4 alkyl-C 1-6 alkoxy, -OC 1-4 alkyl-C 3-20 cycloalkyl, -OC 1-4 alkyl-OC 3-20 cycloalkyl, -OC 1-4 alkyl-3 to 20-membered heterocyclyl, -OC 1-4 alkyl-O-3 to 20-membered heterocyclyl, -OC 1-4 alkyl-C 6-14 aryl, -OC 1-4 alkyl-OC 6-14 aryl, -OC 1-4 alkyl-5-membered or 6-membered monocyclic heteroaryl, -OC 1-4 alkyl-O-5-membered or 6-membered monocyclic heteroaryl, -O -C 1-4 alkyl-8 to 10 bicyclic heteroaryl, -O -C 1-4 alkyl-O-8 to 10 bicyclic heteroaryl, -S(=O) 2 -C 1-6 alkyl, -S(=O) 2 -C 3-20 cycloalkyl, -S(=O) 2 -3 to 20 heterocyclic, -C(=O)OC 1-6 alkyl, -C(=O)OC 3-20 cycloalkyl, -C(=O)-C 1-6 alkyl, -C(=O)-C 3-20 cycloalkyl, -C(=O)-C 6-14 aryl, -NR a1 R b1 , -C(=O)-NR a1 R b1 , -C(=O)-NR d1 -C 1-4 alkyl-R c1 , -OR c1 , -C 1-4 alkyl-S(=O) 2 -C 1-6 alkyl, -C 1-4 alkyl-S(=O) 2 -C 3-20 cycloalkyl, -C 1-4 alkyl-S(=O) 2 -3 to 20 heterocyclic, -C 1-4 alkyl-C(=O)OC 1-6 alkyl, -C 1-4 alkyl-C(=O)OC 3-20 cycloalkyl, -C 1-4 alkyl-C(=O)-C 1-6 alkyl , -C 1-4 alkyl-C(=O)-C 3-20 cycloalkyl, -C 1-4 alkyl-C(=O)-C 6-14 aryl, -C(=O)-5 or 6 monocyclic heteroaryl, -C(=O)-8 to 10 bicyclic Heteroaryl, -C(=O)-C 1-6 alkyl-C 3-20 cycloalkyl, -C(=O)-C 1-6 alkyl-3 to 20-membered heterocyclyl, -C(=O)-C 1-6 alkyl-C 6-14 aryl, -C(=O)-C 1-6 alkyl-5-membered or 6-membered monocyclic heteroaryl, -C(=O)-C 1-6 alkyl-8 to 10-membered bicyclic heteroaryl, -C 1-4 alkyl-NR a1 R b1 , -C 1-4 alkyl-C(=O)-NR a1 R b1 , -C≡CC(=O)-NR a1 R b1 , -C≡CC 1-4 alkyl-C(=O)-NR a1 R b1 , -C 1-4 alkyl-OR c1 , -C 1-4 alkyl-P(=O)-(C 1-6 alkyl) 2 , -P(=O)-(C 1-6 alkyl) 2 , -C 1-4 alkyl-NR d1 -C(=O)-R c1 , -C 1-4 alkyl-NR d1 -C(=O)-NR a1 R b1 , -C 1-4 alkyl-NR d1 -S(=O) 2 -R c1 , -C 1-4 alkyl-S(=O) 2 -NR a1 R b1 , -C 1-4 alkyl-NR d1 -S(=O) 2 -NR a1 R b1 , -NR d1 -C(=O)-R c1 , -NR d1 -C(=O)-C 1-4 alkyl-R c1 , -NR d1 -C(=O)-NR a1 R b1 , Selected from the group consisting of -NR d1 -S(=O) 2 -R c1 , -S(=O) 2 -NR a1 R b1 , -NR d1 -S(=O) 2 -NR a1 R b1 and -P(=O)-(C 1-6 alkyl) 2 ; wherein the C 1-6 alkyl, the C 1-6 alkoxy, the C 2-6 alkenyl, and the C 2-6 alkynyl are each independently optionally substituted by one, two, or three groups selected from halogen, deuterium, cyano, or hydroxy; The C 3-20 cycloalkyl, the 3 to 20-membered heterocyclyl, the C 6-14 aryl, the 5-membered or 6-membered monocyclic heteroaryl, and the 8-membered to 10-membered bicyclic heteroaryl are each independently selectively substituted by 1, 2, 3, or 4 groups selected from group S2; In each of the groups described above, each R a1 and R b1 is independently H, C 1-6 alkyl, C 1-6 alkyl halide, C 1-6 alkyl deuteride, -C 1-4 alkyl-hydroxy, -C 1-4 alkyl-cyano, -C 1-4 alkyl-C 1-6 alkyl halide, -C 1-4 alkyl-deuteride C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-C 1-6 alkoxy halide, -C 1-4 alkyl-deuteride C 1-6 alkoxy, C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-OC 3-6 monocyclic cycloalkyl, ternary to six-membered Monocyclic heterocyclyl, -C 1-4 alkyl-ternary to 6-membered monocyclic heterocyclyl, -C 1-4 alkyl-O-ternary to 6-membered monocyclic heterocyclyl, phenyl, -C 1-4 alkyl-phenyl, 5-membered or 6-membered monocyclic heteroaryl, -C 1-4 alkyl-5-membered or 6-membered monocyclic heteroaryl, 8-membered to 10-membered bicyclic heteroaryl, -C 1-4 alkyl-8-membered to 10-membered bicyclic heteroaryl, -S (=O) 2 -C 1-6 alkyl, -S(=O) 2 -C 3-6 monocyclic cycloalkyl, -S(=O) 2 -ternary to 6-membered monocyclic heterocyclyl, -C 1-4 alkyl-S(=O) 2 -C 1-6 alkyl, -C 1-4 alkyl-S(=O) 2 -C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-S(=O) 2 -3 to 6-membered monocyclic heterocyclyl, -C(=O)-C 1-6 alkyl, -C(=O)-C 3-6 monocyclic cycloalkyl or -C(=O)-3 to 6-membered monocyclic heterocyclyl; The C3-6 monocyclic cycloalkyl, the 3- to 6-membered monocyclic heterocyclyl, the phenyl, the 5- or 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are optionally selected from one or two groups consisting of halogen, hydroxy, carboxyl, nitro, C1-6 alkyl, C1-6 alkyl halides, C1-6 alkyl deuterides, C1-6 alkoxy, C1-6 alkoxy halides, C1-6 alkoxy deuterides, -NH2 , -NHC1-6 alkyl, -N( C1-6 alkyl) 2 , -C1-4 alkyl-P(=O)-( C1-6 alkyl) 2 , and -P(=O)-( C1-6 alkyl) 2 . Replaced by; or Each R a1 and R b1 co-forms a ternary to 20-membered heterocyclyl together with a nitrogen atom connected thereto; said ternary to 20-membered heterocyclyls are each independently optionally substituted by one or two groups selected from the group consisting of halogen, hydroxy, carboxyl, nitro, C 1-6 alkyl, C 1-6 alkyl halogenated, C 1-6 alkyl deuteride , C 1-6 alkoxy, C 1-6 alkoxy halogenated, C 1-6 alkoxy deuteride, -NH 2 , -NHC 1-6 alkyl, -N(C 1-6 alkyl) 2 , -C 1-4 alkyl-P(=O)-(C 1-6 alkyl) 2 and -P(=O)-( C 1-6 alkyl) 2 ; In each of the aforementioned groups, each R d1 is independently H, C 1-6 alkyl or deuterated C 1-6 alkyl; In each of the groups described above, each R c1 is independently H, C 1-6 alkyl, C 1-6 alkyl halogenated, C 1-6 alkyl deuteriumated, C 1-6 alkoxy, C 1-6 alkoxy halogenated, C 1-6 alkoxy deuteriumated, -C 1-4 alkyl-C 1-6 alkyl halogenated, -C 1-4 alkyl-deuteriumated C 1-6 alkyl, -C 1-4 alkyl-C 1-6 alkoxy, -C 1-4 alkyl-C 1-6 alkoxy halogenated, -C 1-4 alkyl-deuteriumated C 1-6 alkoxy, C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl - C 3-6 monocyclic cycloalkyl, -C 1-4 alkyl-OC 3-6 monocyclic cycloalkyl, ternary to 6-membered monocyclic heterocyclyl, -C1-4 alkyl-3 to 6-membered monocyclic heterocyclyl, -C1-4 alkyl-O-3 to 6-membered monocyclic heterocyclyl, phenyl, -C1-4 alkyl-phenyl, 5-membered or 6-membered monocyclic heteroaryl, -C1-4 alkyl-5-membered or 6-membered monocyclic heteroaryl, 8 to 10-membered bicyclic heteroaryl or -C1-4 alkyl-8 to 10-membered bicyclic heteroaryl; The C3-6 monocyclic cycloalkyl, the 3 to 6-membered monocyclic heterocyclyl, the phenyl, the 5 or 6-membered monocyclic heteroaryl, and the 8 to 10-membered bicyclic heteroaryl are selected from one or two groups consisting of halogen, hydroxy, carboxyl, nitro, C1-6 alkyl, C1-6 alkyl halides, C1-6 alkyl deuterides, C1-6 alkoxy, C1-6 alkoxy halides, C1-6 alkoxy deuterides, -NH2 , -NHC1-6 alkyl, -N( C1-6 alkyl) 2 , -C1-4 alkyl-P(=O)-( C1-6 alkyl) 2 , and -P(=O)-( C1-6 alkyl) 2 Optionally substituted; In each of the groups described above, each group of the S2 group is independently deuterium, oxo (=O), thio (=S), =CR e R f , =NR e , halogen, hydroxy, carboxyl, nitro, C 1-6 alkyl, C 1-6 alkyl halide, C 1-6 alkyl deuterium, C 1-6 alkoxy, C 1-6 alkoxy halide, C 1-6 alkoxy deuterium, -NH 2 , -NHC 1-6 alkyl, -N(C 1-6 alkyl) 2 , -(C=O)-NHC 1-6 alkyl, -(C=O)-N(C 1-6 alkyl) 2 , -C 1-4 alkyl-P(=O)-(C 1-6 alkyl) 2 , -P(=O)-(C 1-6 alkyl) 2 , Selected from the group consisting of -(C=O)C 1-6 alkyl and -SF 5 ; In each of the groups described above, the -C 1-4 alkyl- is unsubstituted; or 1, 2, 3, or 4 hydrogen atoms on the -C 1-4 alkyl- are each independently substituted by a group selected from halogen, cyano, hydroxy, C 1-6 alkyl, halogenated C 1-6 alkyl, deuteriumated C 1-6 alkyl, -CH 2 -hydroxy, -CH 2 -cyano, or phenyl; or two hydrogen atoms on the same carbon atom of the C 1-4 alkyl are simultaneously substituted by -(CH 2 ) j - to form a cycloalkyl, where j is 2, 3, 4, 5, or 6; or two hydrogen atoms on the same carbon atom of the C 1-4 alkyl are simultaneously substituted by =CR e R f ; In each of the aforementioned groups, R e is independently H, a halogen, a C1-6 alkyl, a C1-6 alkyl halide, or a C1-6 alkyl deuteride; In each of the aforementioned groups, R f is independently H, a halogen, a C1-6 alkyl, a C1-6 alkyl halide, or a C1-6 alkyl deuteride; In each of the groups described above, one or more (e.g., 1, 2, 3, or 4) ring atoms of the ternary to eighth heterocyclil, ternary to tenth heterocyclil, or ternary to eighth monocyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, or 4) ring atoms of the C 1-6 heteroalkyl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; and one or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the henary to twelveth cyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; One or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 3 to 20-membered heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, or 4) ring atoms of the above 5-membered or 6-membered monocyclic heteroaryl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; one or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 8 to 10-membered cyclic heteroaryl are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; and one or more (e.g., 1, 2, 3, or 4) ring atoms of the above 3 to 6-membered monocyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; One or more (e.g., 1, 2, 3, 4, or 5) ring atoms of the above 5 to 15-membered tricyclic heterocyclil are heteroatoms selected from nitrogen, oxygen, sulfur, or phosphorus; Here, if the ring atom is a sulfur atom, the sulfur atom is optionally substituted by one or two groups selected from oxo and =NR e ; the definition of R e is the same as before; Here, where the ring atom is a phosphorus atom, the corresponding phosphorus atom is selectively substituted by one or two groups selected from oxo and =NR e ; the definition of R e is the same as above, a compound or its stable deuterated derivative or its stereoisomer, or its pharmaceutically acceptable salt, solvate or prodrug.
  6. In claim 1, where R 4a is a -C 1-6 alkyl-C 1-6 alkoxyne, a compound or a stable deuterated derivative thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof.
  7. In paragraph 1, where R 5 is hydrogen, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or A compound selected from, or a stable deuterated derivative thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
  8. In claim 1, wherein R3 is a compound or a stable deuterated derivative thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, where R3 is hydrogen, C1-6 alkyl, C1-6 alkyl halogenated, C1-6 alkyl deuteride or C3-6 cycloalkyl.
  9. A compound or a stable deuterated derivative thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R1 is hydrogen and R2 is hydrogen.
  10. In paragraph 1, where, L1 is , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or A compound selected from, or a stable deuterated derivative thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
  11. In paragraph 1, where, R 6 is , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or A compound selected from, or a stable deuterated derivative thereof or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
  12. In claim 1, the compound is a compound selected from Table A, Table B, or Table C, a stable deuterated derivative thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
  13. A pharmaceutical composition comprising: a compound according to any one of claims 1 to 12, a stable deuterated derivative thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof; and a pharmaceutically acceptable carrier.
  14. The use of a compound according to any one of claims 1 to 12, a stable deuterated derivative thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition according to claim 13, in the manufacture of a drug for preventing and/or treating diseases or pathologies associated with RAS protein activity.
  15. In Clause 14, the disease or pathology associated with the above RAS protein activity is cancer.
  16. In paragraph 15, the above cancer is a pancreatic cancer, colorectal cancer, non-small cell lung cancer, acute myeloid leukemia, multiple myeloma, thyroid adenocarcinoma, myelodysplastic syndrome, squamous cell lung cancer, esophageal cancer, ovarian cancer, uterine cancer, melanoma, bladder cancer, or head and neck cancer.

Description

Macrocyclic compounds, methods of preparation thereof, and uses **Macrocyclic compounds and their uses** Citation of related applications The present application claims priority of the prior application with patent application number 202311130834X filed with the National Intellectual Property Administration of China on September 1, 2023; the prior application with patent application number 2024104662832 filed with the National Intellectual Property Administration of China on April 17, 2024; the prior application with patent application number 2024106442663 filed with the National Intellectual Property Administration of China on May 22, 2024; the prior application with patent application number 2024108449718 filed with the National Intellectual Property Administration of China on June 26, 2024; and the prior application with patent application number 2024111714441 filed with the National Intellectual Property Administration of China on August 23, 2024. The entire contents of five prior applications are incorporated into the present application by means of citation. Technology field The present disclosure belongs to the field of medicine and, specifically, relates to a macrocyclic compound capable of inhibiting RAS protein activity, a method for preparing the same, and uses. The RAS gene (Rat sarcoma viral oncogene homolog) codes for a small GTP hydrolase family protein with a molecular weight of approximately 21 kDa. The mammalian RAS family includes three members—HRAS, KRAS, and NRAS—which act as molecular switches in various cellular signaling pathways. When RAS binds to GDP, it enters an inactive state known as dormancy or closure. When a cell is exposed to a specific growth-promoting stimulant, RAS is induced to convert the bound GDP to GTP; subsequently, it becomes activated, recruits and activates other downstream target proteins (e.g., Raf and PI3K), and promotes cell proliferation. RAS proteins possess the intrinsic activity of hydrolyzing GTP to GDP (thereby converting itself into an inactive state), but the conversion rate is relatively slow. However, when it binds to GTP hydrolase activating protein (GAP), the interaction between the two significantly accelerates the rate at which the RAS protein converts GTP to GDP, causing the RAS to rapidly return to an inactive state at the end of cell stimulation, thereby blocking signaling pathway transmission. RAS gene mutations have been found in approximately 30% of human tumors; among them, KRAS mutations are the most common, accounting for about 85%, while NRAS and HRAS account for 12% and 3%, respectively. KRAS mutations account for the majority in pancreatic cancer (86%), colorectal cancer (41%), and lung cancer (32%); NRAS mutations are common in melanoma and acute myeloid leukemia; and HRAS mutations are common in bladder cancer and head and neck cancer. In tumors, RAS gene mutations occur primarily through point mutations. Over 150 different types of RAS point mutations have been identified, among which mutations at G12, G13, and Q61 are the most common. These pathogenic mutations typically affect the interaction between RAS and GAP and the endogenous GTP hydrolase activity of RAS, causing the mutated RAS protein to exist in an activated form within the cell that binds primarily to GTP. Consequently, the signaling pathway mediated by this remains in a continuously activated state, leading to uncontrolled cell proliferation and ultimately promoting tumor formation. Currently, regarding KRAS G12C mutations, AMG510 and MRTX849, targeted drugs for the treatment of KRAS G12C-mutated non-small cell lung cancer, have received marketing approval. However, there are no approved corresponding targeted drugs for KRAS G12D and KRAS G12V mutations, which frequently occur in pancreatic and colorectal cancers, and NRAS and HRAS mutations, which are common in melanoma and head and neck cancers. Therefore, researching and developing effective inhibitors for various RAS mutations is of great clinical value and is both a key and challenging task in the field of new drug research and development. The present disclosure provides a RAS inhibitor capable of inhibiting RAS activity by driving the formation of a high-affinity ternary complex between a RAS protein and a cytoplasmic chaperone protein (e.g., cyclophilinA) and through non-covalent interactions with both the RAS protein and the cytoplasmic chaperone protein. The RAS inhibitor of the present disclosure has advantages such as high activity and low toxicity side effects, and is expected to have excellent physicochemical properties and pharmacokinetic characteristics. A first aspect of the present disclosure provides a compound represented by formula (I), a stable deuterated derivative thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt, solvate, or prodrug thereof: (I) In the equation, Ring A is or And; is a phenyl, pentagonal or hexagonal heteroaryl or a pentagonal or hexagonal heterocyclil