Imine compounds as well as preparation method therefor and use thereof

A compound as shown in formula I:

• or an isotopic derivative thereof or a pharmaceutically acceptable salt of any of the foregoing;
• wherein X is N—OR1;
• R1 is hydrogen or C1-6 alkyl, and the C1-6 alkyl is optionally substituted with one or more R1a;
• each R1a is independently halogen, cyano, nitro, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, phenyl, 5- to 6-membered heteroaryl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl, halogenated C2-6 alkynyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, —OR5a, —SR5a, —N(R5a)(R5b), —C(O)R5a, —OC(O)R5a, —C(O)OR5a, —C(O)N(R5a)(R5b), —N(R5c)C(O)R5a, —N(R5c)C(O)N(R5a)(R5b), S(O)2R5a, —N(R5c)S(O)2R5a, —S(O)2N(R5a)(R5b), —Si(R5a)3, —Si(R5a)2(OR5b), —OSi(R5a)3, —Si(R5a)(OR5b)2, —OP(O)(OR5a)(OR5b), —P(O)(OR5a)(OR5b), —OP(O)(OR5a)(R5b), —P(O)(OR5a)(R5b), —OP(O)(R5a)(R5b) or —P(O)(R5a)(R5b);
• R3a is hydrogen, halogen, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, phenyl, 5- to 6-membered heteroaryl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl, halogenated C2-6 alkynyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl or -L1-R3c;
• R3b is hydrogen, halogen, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl, halogenated C2-6 alkynyl, -L1-R3c, —C(O)OR3d, —C(O)N(R3d)(R3e), —S(O)2R3d, —S(O)2N(R3d)(R3e), —P(O)(OR3d)(OR3e), —P(O)(OR3d)(R3e), —P(O)(R3d)(R3e) C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl or 5- to 6-membered heteroaryl, and the C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl or 5- to 6-membered heteroaryl optionally forms a fused ring with additional C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl or 5- to 6-membered heteroaryl;
• wherein the C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl and 5- to 6-membered heteroaryl are optionally substituted with one or more substituents independently selected from halogen, hydroxyl, amino, cyano, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl and halogenated C2-6 alkynyl;
• alternatively, R3a and R3b, together with the carbon atom to which they are attached, form C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl or 3- to 8-membered heterocycloalkenyl, and the C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl and 3- to 8-membered heterocycloalkenyl are optionally substituted with one or more substituents independently selected from halogen, hydroxyl, amino, cyano, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl and halogenated C2-6 alkynyl;
• each L1 is independently —[C(Ra)(Rb)]n—;
• wherein n is 1, 2 or 3;
• Ra and Rb are each independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl;
• alternatively, Ra and Rb, together with the carbon atom to which they are attached, form C3-8 cycloalkyl or 3- to 8-membered heterocycloalkyl;
• wherein the C1-6 alkyl, C3-8 cycloalkyl and 3- to 8-membered heterocycloalkyl are optionally substituted with one or more substituents independently selected from halogen, hydroxyl, amino, cyano, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl and halogenated C2-6 alkynyl;
• each R3c is independently —OR7a, —SR7a, —N(R7a)(R7b), —C(O)R7a, —OC(O)R7a, —C(O)OR7a, —C(O)N(R7a)(R7b), —N(R7c)C(O)R7a, —N(R7c)C(O)N(R7a)(R7b), S(O)2R7a, —N(R7c)S(O)2R7a, —S(O)2N(R7a)(R7b), —Si(R7a)3, —Si(R7a)2(OR7b), —OSi(R7a)3, —Si(R7a)(OR7b)2, —OP(O)(OR7a)(OR7b), —P(O)(OR7a)(OR7b), —OP(O)(OR7a)(R7b), —P(O)(OR7a)(R7b), —OP(O)(R7a)(R7b) or —P(O)(R7a)(R7b);
• L2 is —[C(R10a)(R10b)]t—, wherein one C(R10a)(R10b) moiety is optionally replaced by —O— or —N(R10a)—;
• s is 1 and t is 1;
• alternatively, s is 2 and t is 1;
• alternatively, s is 1 and t is 2;
• R9a and R9b are each independently hydrogen, halogen, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl or halogenated C2-6 alkynyl;
• alternatively, R9a and R9b, together with the atom to which they are attached, form C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl or 3- to 8-membered heterocycloalkenyl;
• alternatively, R9a and R3a are joined to form —CH2— or —CH2CH2—;
• R10a and R10b are each independently hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl or halogenated C2-6 alkynyl;
• alternatively, R10a and R10b, together with the carbon atom to which they are attached, form C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl or 3- to 8-membered heterocycloalkenyl;
• alternatively, R10a and R3a, together with the atom to which they are attached, form C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl or 3- to 8-membered heterocycloalkenyl;
• ring A is or
• wherein the * end is connected to the carbonyl group in formula I, and the # end is connected to ring B in formula I;
• each ---- bond is independently a single bond or a double bond;
• each A1 is independently CH, C(O), N, NH, O, S, N(R4a) or C(R4a);
• each A2 is independently CH, C(O), N, NH, O, S, N(R4b) or C(R4b) A3 is CH, C(O), N, N(R4c) or C(R4c);
• each A4 is independently CH, C(O), N, N(R4d) or C(R4d);
• A5 is CH, N, O, S, NH, C(R4d) or N(R4d);
• each A6 is independently C or N;
• each A7 is independently C or N;
• R4a, R4a, R4c and R4d are each independently halogen, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, phenyl, 5- to 6-membered heteroaryl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl, halogenated C2-6 alkynyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, —OR8a, —SR8a, —N(R8a)(R8b), —C(O)R8a, —OC(O)R8a, —C(O)OR8a, —C(O)N(R8a)(R8b), —N(R8c)C(O)R8a, —N(R8c)C(O)N(R8a)(R8b), —S(O)2R8a, —N(R8c)S(O)2R8a, —S(O)2N(R8a)(R8b), —Si(R8a)3, —Si(R8a)2(OR8b), —OSi(R8a)3, —Si(R8a)(0R8b)2, —OP(O)(OR8a)(OR8b), —P(O)(OR8a)(OR8b), —OP(O)(OR8a)(R8b), —P(O)(OR8a)(R8b), —OP(O)(R8a)(R8b) or —P(O)(R8a)(R8b);
• alternatively, R4a and R4b, together with the atom to which they are attached, form C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl or 5- to 6-membered heteroaryl;
• the C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl and 5- to 6-membered heteroaryl are optionally substituted with one or more substituents independently selected from halogen, hydroxyl, amino, cyano, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl and halogenated C2-6 alkynyl;
• in ring B, G1, G2 and G3 are each independently N or C(R2c);
• R2a, R2b and R2c are each independently hydrogen, halogen, cyano, nitro, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, phenyl, 5- to 6-membered heteroaryl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl, halogenated C2-6 alkynyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, —OR6, —SR6, —N(R6a)(R6b), —C(O)R6a, —OC(O)R6a, —C(O)OR6a, —C(O)N(R6a)(R6b), —N(R6c)C(O)R6a, —N(R6c)C(O)N(R6a)(R6b), —S(O)2R6a, —N(R6c)S(O)2R6a, —S(O)2N(R6a)(R6b), —Si(R6a)3, —Si(R6a)2(OR6b), —OSi(R6a)3, —Si(R6a)(OR6b)2, —OP(O)(OR6a)(OR6b), —P(O)(OR6a)(OR6b), —OP(O)(OR6a)(R6b), —P(O)(OR6a)(R6b), —OP(O)(R6a)(R6b) or —P(O)(R6a)(R6b);
• alternatively, R2b and R2a or R2c, together with the carbon atom to which they are attached, form C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl or 5- to 6-membered heteroaryl;
• the C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl and 5- to 6-membered heteroaryl are optionally substituted with one or more substituents independently selected from halogen, hydroxyl, amino, cyano, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl and halogenated C2-6 alkynyl;
• alternatively, R2a and R4b are joined to form —(CH2)p—, wherein p is 2, 3 or 4, and wherein one or two CH2 moieties are optionally replaced by —O— or —NH—;
• R3d, R3e, R5a, R5b, R6a, R6b, R7a, R7b, R5a and R5b are each independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl or 5- to 6-membered heteroaryl, and the C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl or 5- to 6-membered heteroaryl optionally forms a fused ring with additional C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl or 5- to 6-membered heteroaryl;
• wherein the C1-6 alkyl, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl and 5- to 6-membered heteroaryl are optionally substituted with one or more substituents independently selected from halogen, hydroxyl, amino, cyano, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl, halogenated C2-6 alkynyl, C3-8 cycloalkenyl, 3- to 8-membered heterocycloalkenyl, phenyl and 5- to 6-membered heteroaryl;
• R5c, R6c, R7c and R8c are each independently hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl or halogenated C2-6 alkynyl;
• in the aforementioned heterocycloalkyl, heterocycloalkenyl and heteroaryl, the number of heteroatoms is independently 1, 2, 3 or 4, and each heteroatom is independently N, O, S, Si, P and Se;
• provided that at least one of the following conditions (a), (b), (c), (d), and (e) is satisfied:
• condition (a):
• neither R2a nor R2b is hydrogen;
• moreover, when R2a is C1-6 alkyl, R3a is hydrogen and R3b is a group other than -L1-R3c, then R2b is not C1-6 alkyl;
• condition (b):
• R3a is C1-6 alkyl or -L1-R3c and R3b is -L-R3c;
• alternatively, R3a and R3b, together with the carbon atom to which they are attached, form C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl or 3- to 8-membered heterocycloalkenyl, and the C3-8 cycloalkyl, 3- to 8-membered heterocycloalkyl, C3-8 cycloalkenyl and 3- to 8-membered heterocycloalkenyl are optionally substituted with one or more substituents independently selected from halogen, hydroxyl, amino, cyano, oxo, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, C2-6 alkenyl, halogenated C2-6 alkenyl, C2-6 alkynyl and halogenated C2-6 alkynyl;
• condition (c):
• R3a is hydrogen, C1-6 alkyl or -L1-R3c;
• R3b is -L-R3c;
• ring A is
• wherein the * end is connected to the carbonyl group in formula I, and the # end is connected to ring B in formula I;
• moreover, R2a is not hydrogen;
• wherein each A1 is independently CH, N or C(R4a);
• each A2 is independently CH, N or C(R4b);
• each A3 is independently CH, N or C(R4c);
• each A4 is independently CH, N or C(R4d);
• A5 is O, S, NH or N(R4d);
• condition (d):
• R3b is —CH(C1-6 alkyl)-OH,
• —CH2NHC(O)CH2OH or —CH2OCH2CH2OH;
• condition (e):
• R9a and R3a are joined to form —CH2— or —CH2CH2—.