BTK Degrader and Use Thereof

A compound as shown in formula (I), or an isomer or pharmaceutically acceptable salt thereof:

• wherein,
• A is
• X is selected from N and CH;
• Cy1 is selected from
• and phenyl, wherein the
• and phenyl are unsubstituted or each independently substituted with 1-3 Ra1;
• each Ra1 is independently selected from hydrogen, halogen, hydroxy, carboxyl, amino, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, hydroxy C1-6 alkyl, C1-6 alkylamino, (C1-6 alkyl)2 amino, C2-8 alkenyl, C2-8 alkynyl, C1-6 alkylcarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, and (C1-6 alkyl)2 aminocarbonyl;
• B is -L2-Cy2-L3-(Cy3)p-L4-Cy4-L5-(Cy5)q-;
• p and q are independently 0 or 1;
• C is -L6-Cy6-L7-Cy7-L8-Cy8;
• L1, L2, L3, L4, L5, L6, L7 and L8 are independently selected from a bond, —(CH2)n—(NH)m—, —O—, —S—, —NR2, —CR31R32, —C(O)—, —C(O)O—, —C(O)NR4—, and —C1-6 alkyl-NR5—C(O)—;
• n and m are independently any integer from zero to six;
• R2, R31, R32, R4 and R5 are independently selected from hydrogen, halogen, hydroxy, carboxyl, amino, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, hydroxy C1-6 alkyl, C1-6 alkylamino, (C1-6 alkyl)2 amino, C2-8 alkenyl, C2-8 alkynyl, C1-6 alkylcarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, and (C1-6 alkyl)2 aminocarbonyl, wherein the C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, hydroxy C1-6 alkyl, C1-6 alkylamino, (C1-6 alkyl)2 amino, C2-8 alkenyl, C2-8 alkynyl, C1-6 alkylcarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, and (C1-6 alkyl)2 aminocarbonyl are unsubstituted or optionally substituted with one or more groups independently selected from hydroxy, amino, carboxyl, cyano, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkylamino, (C1-6 alkyl)2 amino, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, C1-6 alkylcarbonyloxy, C3-6 cycloalkyl, C3-6 cycloalkylcarbonyloxy, C2-8 alkynyl, halogenated C1-6 alkyl, C2-8 alkenyl, and halogenated C1-6 alkoxy;
• Cy2 is selected from a 4-6 membered cycloalkyl group, a 4-6 membered heterocyclyl group, a 4-6 membered cycloalkenyl group, a 4-6 membered heterocycloalkenyl group, a 4-6 membered cycloalkyl group substituted with 1-3 Ra2, a 4-6 membered heterocyclyl group substituted with 1-3 Ra2, a 4-6 membered cycloalkenyl group substituted with 1-3 Ra2, and a 4-6 membered heterocycloalkenyl group substituted with 1-3 Ra2, wherein the heteroatoms of the 4-6 membered heterocyclyl group and the 4-6 membered heterocycloalkenyl group are selected from O, N and S;
• Cy3 is selected from a 4-6 membered cycloalkyl group, a 4-6 membered heterocyclyl group, a 4-6 membered cycloalkenyl group, a 4-6 membered heterocycloalkenyl group, a 4-6 membered cycloalkyl group substituted with 1-3 Ra3, a 4-6 membered heterocyclyl group substituted with 1-3 Ra3, a 4-6 membered cycloalkenyl group substituted with 1-3 Ra3, and a 4-6 membered heterocycloalkenyl group substituted with 1-3 Ra3, wherein the heteroatoms of the 4-6 membered heterocyclyl group and the 4-6 membered heterocycloalkenyl group are selected from O, N and S;
• Cy4 is selected from a 4-12 membered cycloalkyl group, a 4-12 membered heterocyclyl group, a 4-12 membered cycloalkenyl group, a 4-12 membered heterocycloalkenyl group, a 4-12 membered cycloalkyl group substituted with 1-3 Ra4, a 4-12 membered heterocyclyl group substituted with 1-3 Ra4, a 4-12 membered cycloalkenyl group substituted with 1-3 Ra4, and a 4-12 membered heterocycloalkenyl group substituted with 1-3 Ra4, wherein the heteroatoms of the 4-12 membered heterocyclyl group and the 4-12 membered heterocycloalkenyl group are selected from O, N and S;
• Cy5 is a 4-6 membered cycloalkyl group, a 4-6 membered heterocyclyl group, a 4-6 membered heterocycloalkenyl group, a 4-6 membered cycloalkyl group substituted with 1-3 Ra5, a 4-6 membered heterocyclyl group substituted with 1-3 Ra5, a 4-6 membered heterocycloalkenyl group substituted with 1-3 Ra5, or
• X1 is N or CRb1;
• X2 is N or CRb2;
• X3 is N or CRb3;
• X4 is N or CRb4;
• X5 is N or CRb5;
• Rb1, Rb2, Rb3, Rb4 and Ra5 are independently selected from hydrogen, halogen, hydroxy, carboxyl, amino, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, hydroxy C1-6 alkyl, C1-6 alkylamino, (C1-6 alkyl)2 amino, C2-8 alkenyl, C2-8 alkynyl, C1-6 alkylcarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, and (C1-6 alkyl)2 aminocarbonyl;
• Cy6 is selected from a 5-6 membered heteroaryl group, a 5-6 membered heterocycloalkenyl group, a 9-10 membered heterocycloalkenyl group, a 9-10 membered heteroaryl group, a 5-6 membered heteroaryl group substituted with 1-3 Ra6, a 5-6 membered heterocycloalkenyl group substituted with 1-3 Ra6, a 9-10 membered fused heterocycloalkenyl group substituted with 1-3 Ra6, and a 9-10 membered fused heteroaryl group substituted with 1-3 Ra5, wherein the heteroatoms of the 5-6 membered heteroaryl group, the 5-6 membered heterocycloalkenyl group, the 9-10 membered fused heterocycloalkenyl group, and the 9-10 membered fused heteroaryl group are selected from O, N and S;
• Cy7 is selected from phenyl, a 5-6 membered heteroaryl group, phenyl substituted with 1-3 Ra7, and a 5-6 membered heteroaryl group substituted with 1-3 Ra7, wherein the heteroatom of the 5-6 membered heteroaryl group is selected from O, N and S;
• Cy8 is selected from phenyl, a 5-6 membered heteroaryl group, phenyl substituted with 1-3 Ra5, and a 5-6 membered heteroaryl group substituted with 1-3 Ra5, wherein the heteroatom of the 5-6 membered heteroaryl group is selected from O, N and S;
• and
• each of Ra2, Ra3, Ra4, Ra5, Ra6, Ra7, and Ra8 is at occurrence, independently selected from hydrogen, halogen, hydroxy, carboxyl, amino, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, C1-6 alkoxy, halogenated C1-6 alkoxy, hydroxy C1-6 alkyl, C1-6 alkylamino, (C1-6 alkyl)2 amino, C2-8 alkenyl, C2-8 alkynyl, C1-6 alkylcarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, and (C1-6 alkyl)2 aminocarbonyl.