Krasg12d inhibitor, preparation method therefor and application thereof

A compound of formula (I):

• Wherein,
• Each L1 at each occurrence is independently selected from bond, —C1-4alkyl-, —CR8R9—, —C1-2alkyl(R8)(OH)—, —C(O)—, —CR8R9O—, —OCR8R9—, —SCR8R9—, —CR8R9S—, —NR8—, —NR8C(O)—, —C(O)NR8—, —NR8C(O)NR9—, —CF2—, —O—, —S—, —S(O)m—, —NR8S(O)m—, —S(O)mNR8—;
• Each R1 at each occurrence is independently selected from phenyl, naphthyl, 5-membered heteroaryl, 6-membered heteroaryl, 7-membered heteroaryl, 8-membered heteroaryl, 9-membered heteroaryl, or 10-membered heteroaryl heteroaryl, each heteroaryl independently at each occurrence containing 1, 2, 3 or 4 heteroatoms selected from N, O, or S;
• each R1 at each occurrence independently and optionally substituted or unsubstituted with 1, 2, 3, 4, 5 or 6 R20;
• Each R20 at each occurrence is independently selected from deuterium, halogen, oxo, —C1-6 alkyl, —C2-6 alkenyl, —C2-alkynyl, —C1-6 alkylene-(halogen)1-3, C1-6 heteroalkyl, —CN, —OR6, —C1-6 alkylene-(OR6)1-3, —O—C1-6 alkylene-(halogen)1-3, —SR6, —S—C1-6 alkylene-(halogen)1-3, —NR6R7, —C1-6 alkylene-NR6R7, —C(═O)R6, —C(═O)OR6, —OC(═O)R6, —C(═O)NR6R7, —NR6C(═O)R7, —S(O)2NR6R7 or —C3-6 carbocyclyl;
• each R20 is independently and optionally substituted or unsubstituted with 1, 2, 3, 4, 5 or 6 substituents selected from deuterium, halogen, —C1-6 alkyl, —C1-6 alkoxy, oxo, —OR6, —NR6R7, —CN, —C(═O)R6, —C(═O)OR6, —OC(═O)R6, —C(═O)NR6R7, —NR6C(═O)R7 or —S(O)2NR6R7.
• Each X1, X2, X3, X4, X5 is independently selected from N, CR21 at each occurrence;
• Each R21 is independently selected from H, D, cyano, halogen, C1-6 alkyl, COOH, NHCOH, CONH2, OH or —NH2;
• Each R18 is independently selected from H, D, cyano, halogen, C1-6 alkyl, COOH, NHCOH, CONH2, OH or —NH2;
• Each L2 is independently selected at each occurrence from bond, OC0-6 alkyl, NC0-6 alkyl, C1-6 alkyl, COC0-6 alkyl or SC0-6 alkyl;
• Each R19 is independently selected from
• —C1-6 alkyl, —C2-6 alkenyl, —C2-alkynyl, —C1-6 alkylene-(halogen)1-3, C1-6 heteroalkyl , —CN, —OR6, —C1-6 alkylene-(OR6)1-3, —O—C1-6 alkylene-(halogen)1-3, —SR6, —S—C1-6 alkylene Base-(halogen)1-3, —NR6R7, —C1-6 alkylene-NR6R7, —C(═O)R6, —C(═O)OR6, —OC(═O)R6, —C(═O)NR6R7, —NR6C(═O)R7, —S(O)2NR6R7, —C3-6 carbocyclyl, 3-8 membered heterocycle;
• 3-8 membered heterocycle independently at each occurrence contains 1, 2, 3 or 4 heteroatoms selected from N, O, or S;
• each R19 is independently and optionally are substituted or unsubstituted with 1, 2, 3, 4, 5 or 6 substituents selected from deuterium, halogen, —C1-6alkane base, —C1-6alkoxy, oxo, —OR6, —NR6R7, —CN, —C(═O)R6, —C(═O)OR6, —OC(═O)R6, —C(═O) Substituents of NR6R7, —NR6C(═O)R7 or —S(O)2NR6R7.
• Each ring A is a C3-10 carbocyclic ring, and the
• can be attached to the same carbon atom or to a different atom of the ring A;
• Each R2 is —OR6, —NR6R7, —SR6, —S(═O)R6, —S(═O)2R6, 5-10 membered heteroaryl or 3-10 membered heterocyclyl, each heterocyclyl and heteroaryl at each occurrence independently contain 1, 2, 3 or 4 heteroatoms selected from N, O, S, S═O or S(═O)2, each R2 at each occurrence independently and optionally substituted or unsubstituted with 1, 2, 3, 4, 5 or 6 R22;
• Each R3 and R4 at each occurrence is independently selected from deuterium, hydrogen, halogen, —C1-6 alkyl, —C2-6 alkenyl, —C2-6 alkynyl, oxo, —OR6, —NR6R7, —CN, —C(═O)R6, —C(═O)OR6, —OC(═O)R6, —C(═O)NR6R7, —NR6C(═O)R7 or —S(O)2NR6R7 or —C3-10 carbocyclyl, each heterocyclyl and heteroaryl at each occurrence independently contain 1, 2, 3 or 4 heteroatonsselected from N, O, S, S═O or S(═O)2;
• each R3 and R4 at each occurrence is independently optionally substituted or unsubstituted with 1, 2, 3, 4, 5 or 6 substituents selected from deuterium, halogen, oxo, —C1-6 alkyl, —C1-6 alkoxy, oxo, —OR6, —NR6R7, —CN, —C(═O)R6, —C(═O)OR6, —OC(═O)R6, —C(═O)NR6R7, —NR6C(═O)R7 or —S(O)2NR6R7;
• Each R5 at each occurrence is independently selected from deuterium, halogen, oxo, —C1-6 alkyl, —C1-6 alkylene-(halogen)1-3, C1-6 heteroalkyl, —CN , —OR6, —C1-6 alkylene-(OR6)1-3, —O—C1-6 alkylene-(halogen)1-3, —SR6, —S—C1-6 alkylene-(Halogen)1-3, —NR6R7, —C1-6 alkylene-NR6R7, —C(═O)R6, —C(═O)OR6, —OC(═O)R6, —C(═O)NR6R7, —NR6C(═O)R7, —S(O)2NR6R7 or —C3-6 carbocyclyl, each heterocyclyl and heteroaryl independently at each occurrence contains 1, 2, 3 or 4 options A heteroatom from N, O, S, S═O or S(═O)2;
• each R3 and R4 at each occurrence independently and optionally substituted or unsubstituted with 1, 2, 3, 4, 5 or 6 substituents selected from deuterium, halogen, oxo, —C1-6 alkyl, —C1-6 alkoxy, oxo, —OR6, —NR6R7, —CN, —C(═O)R6, —C(═O)OR6, —OC(═O)R6, —C(═O)NR6R7, —NR6C(═O)R7 or —S(O)2NR6R7;
• Each R6 and R7 at each occurrence is independently selected from hydrogen or —C1-6 alkyl, each R6 and R7 is independently optionally substituted with 1, 2, 3, 4, 5 or 6 R22 or not or R7 and R7 together with the N atom to which they are connected together form a 3-10-membered heterocycle, and the 3-10-membered heterocycle may further comprise 1, 2, 3 or 4 selected from N, O, S, A heteroatom of S(═O) or S(═O)2, and the 3-10 membered heterocycle is independently optionally substituted or unsubstituted by 1, 2, 3, 4, 5 or 6 R22;
• Each R22 at each occurrence is independently selected from deuterium, halogen, oxo, —C1-6alkyl, —C1-6alkylene-(halogen)1-3, C1-6heteroalkyl, —CN , —O—C1-6 alkyl, —C1-6 alkylene-(O—C1-6 alkyl1-3, —O—C1-6 alkylene-(halogen)1-3, —S—C1-6 alkyl, —S—C1-6 alkylene-(halogen)1-3, —N—C1-6 alkyl—C1-6 alkyl, —C1-6 alkylene-NC1-6 alkyl base C1-6 alkyl, —C(═O)C1-6 alkyl, —C(═O)OC1-6 alkyl, —OC(═O)C1-6 alkyl, —C(═O)NC1-6 alkyl C1-6 alkyl, —NC1-6 alkyl C(═O)C1-6 alkyl, —S(O)2NC1-6 alkyl C1-6 alkyl or —C3-6 carbocyclyl;
• s is selected from 0, 1, 2, 3, 4, 5 or 6;
• p is selected from 0, 1, 2, 3, 4, 5 or 6;
• q is selected from 0, 1, 2, 3, 4, 5 or 6;
• m is selected from 1, 2, 3;
• n is selected from 1, 2, 3
• Y is absent or selected from 3-8 membered cycloalkyl, 3-8 membered heterocycloalkyl, 5-12 membered fused alkyl, 5-12 membered fused heterocyclyl, 5-12 membered spirocyclyl, 5-12 membered Membered spiroheterocyclyl, aryl or heteroaryl, each heterocycloalkyl, fused heterocyclyl, spiroheterocyclyl, heteroaryl at each occurrence independently contains 1, 2, 3 or 4 heteroatoms selected from N, O, or S, wherein the cycloalkyl, heterocycloalkyl, spiro, fused ring, fused heterocyclyl, spiroheterocyclyl, aryl, or heteroaryl group is optionally replaced by one or more G1s;
• G1 and G2 are each independently selected from deuterium, cyano, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl or 3-8 membered heterocyclyl, C6-10 aryl, 5-10 membered heteroaryl, —OR8, —OC(O)NR8R9, —C(O)OR8, —C(O)NR8R9, —C(O)R8, —NR8R9, —NR8C(O)R9, —NR8C(O)NR9R10, —S(O)iR8 or —NR8S(O)iR9, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl is optionally substituent with 1 or more deuterium, cyano, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl or 3-8 membered heterocyclyl, C6-10-aryl, 5-10-membered heteroaryl, —OR11, —OC(O)NR11R12, —C(O)OR11, —C(O)NR11R12, —C(O)R11, —NR11R12, —NR11C(O)R12, —NR11C(O)NR12R13, —S(O)iR11 or —NR11S(O)iR12;
• R8, R9, R10, R11, R12 and R13 are each independently selected from hydrogen, deuterium, cyano, halogen, C1-6 alkyl, C3-8 cycloalkyl or 3-8 membered monocyclic heterocyclyl, monocyclic heterocyclyl aryl or phenyl;
• and i is 1 or 2.