Multi-targeting degrader and use thereof

Abstract

The present application relates to the field of pharmaceutical chemistry. Provided are a multi-targeting degrader and the use thereof, and particularly provided are a compound as shown in formula (IA), and a stereoisomer, N-oxide, deuterated derivative and pharmaceutically acceptable salt thereof, wherein the definition of each substituent in the formula is detailed in the description. The compound of formula (IA) can degrade the BTK protein and / or IRAK4 protein, can simultaneously degrade the BTK and IRAK4 proteins in various tumor cells and efficiently inhibit tumor cell proliferation and induce tumor cell apoptosis, and can provide a new drug for treating cancers and other autoimmune diseases.

Description

This application claims priority to Chinese Patent Application No. 2024101782052, filed on February 8, 2024; Chinese Patent Application No. 2024106069292, filed on May 15, 2024; and Chinese Patent Application No. 2025100793872, filed on January 17, 2025, the disclosure of each of which is incorporated herein by reference in its entirety. TECHNICAL FIELD The present application relates to the field of pharmaceutical chemistry, and particularly to a multi-target degrader and a preparation method and use thereof. BACKGROUND ART Interleukin-1 receptor-associated kinase 4 (IRAK4) is a serine / threonine-specific protein kinase. As an important mediator at the intersection of interleukin-1 (IL-1) family receptors and Toll-like receptor (TLR) signaling, IRAK4 possesses a wide range of physiological functions. IRAK4 undergoes autophosphorylation and activates the kinase activities of other IRAKs, thereby activating downstream signaling pathways (such as NF-kappa B, JNK, and p38), which in turn promote the secretion of inflammatory cytokines and the proliferation and differentiation of immune cells. IRAK4 plays a bridging role in the entire signaling pathway, altering its activity through conformational changes and post-translational modifications. In the Myddosome, IRAK4 is activated by trans-autophosphorylation, and then activates IRAK1 / 2 through phosphorylation, which subsequently activates downstream signaling pathways and produces pro-inflammatory factors. Previous pharmacological studies have shown that IRAK4 plays a key role in various inflammatory diseases, such as arthritis, atherosclerosis, Alzheimer's disease, gout, systemic lupus erythematosus, and psoriasis. Some studies have shown that mutating IRAK4 or inhibiting its activity in animal models exhibits therapeutic effects on inflammatory diseases (such as septic shock, SLE, cardiovascular diseases, and Alzheimer's disease). Therefore, IRAK4 has currently become an important drug development target, and the treatment of various diseases such as inflammatory diseases, autoimmune diseases, and tumors can be achieved by inhibiting IRAK4 activity. Bruton's tyrosine kinase (BTK) is a non-receptor cytoplasmic tyrosine kinase of the Tec family. In B lymphocytes, BTK activity is essential for B cell receptor (BCR)-mediated activation, which can induce cell development, antibody and cytokine production, and co-stimulatory molecule expression. BTK is a key kinase that links BCR signaling, FcR signaling, TLR signaling, and chemokine receptor signaling. The central role of BTK in B cell signaling and function makes it an important drug development target for B cell malignancies as well as autoimmune and inflammatory diseases. Currently, several BTK inhibitors that have been approved for marketing are primarily indicated for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and other B cell malignancies, as well as graft-versus-host disease (GvHD). Currently, various inflammatory or autoimmune diseases driven by B cells or myeloid cells are gradually becoming important indications for clinical research on BTK inhibitors, and multiple BTK molecules have entered clinical studies. However, to date, no BTK inhibitor has been approved for inflammatory or autoimmune diseases. Currently, in the research on activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL), it has been found that ABC-DLBCL patients with the MyD88L265P mutation exhibit poor response to BCR inhibitors due to aberrant MyD88 signaling. Moreover, extensive research data from Bayer, Nimbus, and AstraZeneca have demonstrated that in ABC-DLBCL xenograft animal models, the combination of an IRAK4 inhibitor and a BTK inhibitor significantly improves the in vivo efficacy of Ibrutinib. If the aberrations in both the BCR pathway and the MyD88 pathway can be effectively inhibited simultaneously, it would be a more effective approach for treating ABC-DLBCL. Therefore, the development of dual-target inhibitors of IRAK4 and BTK can achieve dual benefits in blocking the NF-kB pathway, which is a highly efficient and effective strategy from a therapeutic mechanism perspective, providing a potentially effective new treatment method for ABC-DLBCL patients. PROTAC (Proteolysis Targeting Chimera) technology, also known as protein-targeted degradation technology, is an emerging chemical probe or drug discovery approach that induces targeted protein degradation using the ubiquitin-proteasome system. PROTAC technology employs bifunctional small molecules that simultaneously bind to target proteins and E3 ligases, causing the target proteins to be recognized by E3 ligases and tagged with ubiquitin, which are then degraded by the proteasome. These bifunctional compounds provide the possibility of temporarily controlling protein expression and have been widely used in the research and treatment of diseases including tumors, autoimmune diseases, and anti-infective therapies. SUMMARY OF THE INVENTION The present application achieves degradation of dual target proteins BTK and IRAK4 through protein-targeted degradation technology, with good degradation activity and high selectivity. The corresponding bifunctional compounds can efficiently achieve degradation of both target proteins, while the molecules possess better druggability, higher bioavailability, and higher drug exposure, providing a more sufficient material basis for the potential clinical application of such compounds. The present application has discovered a series of carboxylic acid fragments with structural diversity that exhibit efficient degradation activity against target proteins such as IRAK4 and BTK. Such carboxylic acid fragments have not been explicitly reported in the prior art, which constitutes an innovation in the PROTAC drug moiety. This is the primary innovation point. Additionally, the combination based on the E3 moiety and the linker moiety is also different, which constitutes a secondary innovation point. The present application achieves degradation of dual target proteins BTK and IRAK4 through protein-targeted degradation technology, with good degradation activity and high selectivity. The degradation activity against target proteins exhibits a good concentration-dependent relationship with compound concentration. The corresponding bifunctional compounds can efficiently achieve degradation of both target proteins, while the molecules possess better druggability, higher bioavailability, and higher drug exposure, providing a more sufficient material basis for the potential clinical application of such compounds. Specifically, in one aspect, the present application provides a compound of Formula (IA), a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof: Rx                        (IA) wherein, Ring B is wherein “' /  ” is a single bond or a double bond; W1, W2, W3, W4 are each independently C=O, CH, CH2, O, N, CR1, or NR1; W5, W6, W7 are each independently N or CH; R1 is hydrogen, halogen, C1-6 alkyl, or C1-6 haloalkyl; Rx is hydrogen, C1-6 alkoxy, -C(O)NRx1Rx2, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkoxy is optionally substituted with one or more C3-6 cycloalkyl groups; said 4- to 8-membered nitrogen-containing heterocycloalkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more substituents selected from halogen, hydroxyl, C1-6 alkyl, or hydroxy-substituted C1-6 alkyl; said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or S as ring atoms; Rx1, Rx2 are each independently hydrogen or C1-6 alkyl; Lx is -C(O)NH- or -CH2-NH-; Ring A is: (i) an 8- to 10-membered bicyclic heteroaryl; said 8- to 10-membered bicyclic heteroaryl is formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring; (ii) an 8- to 10-membered bicyclic heteroaryl; said 8- to 10-membered bicyclic heteroaryl is formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring; (iii) a 9- or 10-membered bicyclic heteroaryl; said 9- or 10-membered bicyclic heteroaryl is formed by fusion of a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring; (iv) a 5- or 6-membered monocyclic heteroaryl; or, (v) C6-8 aryl; or, Ring A is: wherein S1, S2, S3, S4, S5, S6, S7, S8 are each independently selected from CH2, CH, NH, N, O, or S; S9, S10 are each independently selected from N or CH; q1, q2 are each independently 0, 1, or 2; Ry is hydrogen, halogen, hydroxyl, =O, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C3-6 cycloalkyl, -O-Ra-, -NRbRc, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more R1 substituents; R1 is halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, -OC(O)-C1-6 alkyl, -OP(O)(OH)2, or a 4- to 12-membered heterocycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl, or C1-6 alkoxy; preferably, R1 is halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, -OC(O)-C1-6 alkyl, -OP(O)(OH)2, or a 4- to 12-membered heterocycloalkyl, wherein said 4- to 12-membered heterocycloalkyl is optionally substituted with one or more substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl, or C1-6 alkoxy; Ra is C1-6 alkyl or C6-8 aryl; Rb, Rc are each independently hydrogen or C1-3 alkyl; y is 0, 1, 2, 3, or 4; L is ; wherein the position indicated by “    ” is the point of attachment to E3, and the position indicated by is the point of attachment to Ring B; Q1, Q2, Q3 are each independently a 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl, wherein said 4- to 12-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom; said 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl is optionally substituted with one or more substituents selected from halogen and hydroxyl; L1, L2, L3, L4 are each independently -CRL1RL2-, -NRL3-, -CRL1RL2-NRL3-, -NRL3-CRL1RL2-, or -ORL4; RL1, RL2, RL3, RL4 are each independently hydrogen, halogen, =O, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkynyl; m1, m2, m3, m4, m5, m6, m7 are each independently 0 or 1; E3 is an E3 ubiquitin ligase binding moiety. . .. In one embodiment, L is                m5                             ^  ; wherein the position indicated by “    ” is the point of attachment to E3, and the position indicated by “      ” is the point of attachment to Ring B; Q1, Q2, Q3 are each independently a 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl, wherein said 4- to 12-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom; said 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl is optionally substituted with one or more substituents selected from halogen and hydroxyl; L1, L2, L3, L4 are each independently -CRL1RL2-, -NRL3-, -CRL1RL2-NRL3-, -NRL3-CRL1RL2-, or -ORL4; RL1, RL2, RL3, RL4 are each independently hydrogen, halogen, =O, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkynyl; m1, m2, m3, m4, m5 are each independently 0 or 1; E3 is an E3 ubiquitin ligase binding moiety. In one aspect, the present application provides a compound of Formula (I), a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof: A /   '   ' y wherein, “' /  ” is a single bond or a double bond; (I) W1, W2, W3, W4 are each independently C=O, CH, CH2, O, N, CR1, or NR1; R1 is hydrogen, halogen, C1-6 alkyl, or C1-6 haloalkyl; Rx is hydrogen or a 4- to 8-membered nitrogen-containing heterocycloalkyl, wherein said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or S as ring atoms; Lx is -C(O)NH- or -CH2-NH-; Ring A is: (i) an 8- to 10-membered bicyclic heteroaryl; said 8- to 10-membered bicyclic heteroaryl is formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring; (ii) an 8- to 10-membered bicyclic heteroaryl; said 8- to 10-membered bicyclic heteroaryl is formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring; (iii) a 9- or 10-membered bicyclic heteroaryl; said 9- or 10-membered bicyclic heteroaryl is formed by fusion of a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring; (iv) a 5- or 6-membered monocyclic heteroaryl; or, (v) C6-8 aryl; Ry is hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, -O-Ra-, -NRbRc, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said 5- or 6-membered monocyclic heteroaryl or C6-8 aryl is optionally substituted with one or more R1 substituents; R1 is halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, or C3-6 cycloalkyl; Ra is C1-6 alkyl or C6-8 aryl; Rb, Rc are each independently hydrogen or C1-3 alkyl; y is 0, 1, 2, 3, or 4; ..... y L is                  m5                                **   ; wherein the position indicated by “'    ” is the point of attachment to E3, and the position indicated by “      ” is the point of attachment to Ring B; Q1, Q2, Q3 are each independently a 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl, wherein said 4- to 12-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom; said 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl is optionally substituted with one or more substituents selected from halogen and hydroxyl; L1, L2, L3, L4 are each independently -CRL1RL2-, -NRL3-, -CRL1RL2-NRL3-, -NRL3-CRL1RL2-, or -ORL4; RL1, RL2, RL3, RL4 are each independently hydrogen, halogen, =O, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkynyl; m1, m2, m3, m4, m5 are each independently 0 or 1; E3 is an E3 ubiquitin ligase binding moiety. In one aspect, the present application provides a compound of Formula (I-1), a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof: (I-1) wherein, Rx is hydrogen, C1-6 alkoxy, -C(O)NRx1Rx2, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkoxy is optionally substituted with one or more C3-6 cycloalkyl groups; said 4- to 8-membered nitrogen-containing heterocycloalkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more substituents selected from halogen, hydroxyl, C1-6 alkyl, or hydroxy-substituted C1-6 alkyl; said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or S as ring atoms; Rx1, Rx2 are each independently hydrogen or C1-6 alkyl; Lx is -C(O)NH- or -CH2-NH-; Ring A is: (i) an 8- to 10-membered bicyclic heteroaryl; said 8- to 10-membered bicyclic heteroaryl is formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring; (ii) an 8- to 10-membered bicyclic heteroaryl; said 8- to 10-membered bicyclic heteroaryl is formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring; (iii) a 9- or 10-membered bicyclic heteroaryl; said 9- or 10-membered bicyclic heteroaryl is formed by fusion of a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring; (iv) a 5- or 6-membered monocyclic heteroaryl; or, (v) C6-8 aryl; or, Ring A is: wherein S1, S2, S3, S4, S5, S6, S7, S8 are each independently selected from CH2, CH, NH, N, O, or S; S9, S10 are each independently selected from N or CH; q1, q2 are each independently 0, 1, or 2; Ry is hydrogen, halogen, hydroxyl, =O, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C3-6 cycloalkyl, -O-Ra-, -NRbRc, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more R1 substituents; R1 is halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, -OC(O)-C1-6 alkyl, -OP(O)(OH)2, or a 4- to 12-membered heterocycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl, or C1-6 alkoxy; preferably, R1 is halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, -OC(O)-C1-6 alkyl, -OP(O)(OH)2, or a 4- to 12-membered heterocycloalkyl, wherein said 4- to 12-membered heterocycloalkyl is optionally substituted with one or more substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl, or C1-6 alkoxy; Ra is C1-6 alkyl or C6-8 aryl; Rb, Rc are each independently hydrogen or C1-3 alkyl; y is 0, 1, 2, 3, or 4; L is m5                   m      '   ; wherein the position indicated by “ ” is the point of attachment to E3, and the position indicated by “      ” is the point of attachment to Ring B; Q1, Q2, Q3 are each independently a 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl, wherein said 4- to 12-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom; said 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl is optionally substituted with one or more substituents selected from halogen and hydroxyl; L1, L2, L3, L4 are each independently -CRL1RL2-, -NRL3-, -CRL1RL2-NRL3-, -NRL3-CRL1RL2-, or -ORL4; RL1, RL2, RL3, RL4 are each independently hydrogen, halogen, =O, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkynyl; m1, m2, m3, m4, m5, m6, m7 are each independently 0 or 1; E3 is an E3 ubiquitin ligase binding moiety. In one embodiment, the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A is a structure represented by Formula (A1) or Formula (A2): wherein U1 is N or CRU1; U2 is N or CRU2; U3 is N or CRU3; U4 is N or CRU4; U5 is N or CRU5; U6 is N or CRU6; U7 is N or CRU7; U8 is N or CRU8; and at least one of U1, U2, U3, U4, U5, U6, U7, U8 is N; RU1, RU2, RU3, RU4, RU5, RU6, RU7, RU8 are each independently hydrogen or Ry. In one embodiment, the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A is a structure represented by Formula (A3) or Formula (A4): (A3); (A4); wherein Z1 is N or CRZ1; Z2 is NRZ2, O, or S; Z3 is N or CRZ3; Z4 is N or CRZ4; Z5 is N or CRZ5; Z6 is N or CRZ6; and at least one of Z3, Z4, Z5, Z6 is N; RZ0, RZ1, RZ2, RZ3, RZ4, RZ5, RZ6 are each independently hydrogen or Ry. In one embodiment, the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A is a structure represented by Formula (A5): xJ P3^^-P2 X ? Pl P4 (A5); wherein P1 is NRP1, O, or S; P2 is NRP2, O, or S; P3 is N or CRP3; P4 is N or CRP4; and at least one of P3, P4 is N; RP1, RP2, RP3, RP4 are each independently hydrogen or Ry. In one embodiment, the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A is a structure represented by Formula (A6): / V.    .V8 V2^        v7 -H         H *V3^ ^V9<. ^V6 V3      V5 (A6); wherein V1 is N or CRV1; V2 is N or CRV2; V3 is N or CRV3; V4 is N or CRV4; V5 is N or CRV5; V6 is N or CRV6; V7 is N or CRV7; V8 is N or CRV8; V9 is N or CRV9; and at least one of V1, V2, V3, V4, V5, V6, V7, V8, V9 is N; RV1, RV2, RV3, RV4, RV5, RV6, RV7, RV8, RV9 are each independently hydrogen or Ry. In one embodiment, the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring in Ring A is a structure represented by Formula (A7), Formula (A8), Formula (A9), Formula (A10), or Formula (A11): (A7); (A8); (A9); (A10); (A11); wherein H1 is N or CRH1; H2 is N or CRH2; H3 is N or CRH3; H4 is NRH4a, O, S, or CRH4bRH4c; H5 is NRH5a, O, S, or CRH5bRH5c; H6 is NRH6a, O, S, or CRH6bRH6c; H7 is NRH7a, O, S, or CRH7bRH7c; RH0, RH1, RH2, RH3, RH4a, RH4b, RH4c, RH5a, RH5b, RH5c, RH6a, RH6b, RH6c, RH7a, RH7b, RH7c are each independently hydrogen or Ry; G1 is N, O, S, or CRG1; G2 is NRG2a, O, S, or CRG2bRG2c; G3 is NRG3a, O, S, or CRG3bRG3c; G4 is NRG4a, O, S, or CRG4bRG4c; G5 is NRG5a, O, S, or CRG5bRG5c; G6 is NRG6a, O, S, or CRG6bRG6c; RG0, RG1, RG2a, RG2b, RG2c, RG3a, RG3b, RG3c, RG4a, RG4b, RG4c, RG5a, RG5b, RG5c, RG6a, RG6b, RG6c are each independently hydrogen or Ry. In one embodiment, the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring is a structure represented by Formula (A12) or Formula (A13): (A12); (A13); wherein M1 is N or CRM1; M2 is N or CRM2; M3 is N or CRM3; M4 is NRM4; M5 is NRM5a, O, S, or CRM5bRM5c; M6 is NRM6a, O, S, or CRM6bRM6c; M7 is NRM7a, O, S, or CRM7bRM7c; M8 is NRM8a, O, S, or CRM8bRM8c; RM1, RM2, RM3, RM4, RM5a, RM5b, RM5c, RM6a, RM6b, RM6c, RM7a, RM7b, RM7c, RM8a, RM8b, RM8c are each independently hydrogen or Ry; p1, p2 are each independently 0, 1, or 2. In one embodiment, in the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A, the two 5- or 6-membered monocyclic heteroaryl rings are each independently selected from the group consisting of: said groups being optionally substituted with one or more Ry substituents; “    ” represents the carbon atom or heteroatom to which the ring is attached, which is an adjacent atom pair of the carbon atom or heteroatom shared by an other ring when the ring is fused to the other ring. In one embodiment, in the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring in Ring A, the 5- or 6-membered monocyclic heteroaryl ring is selected from the group consisting of: said groups being optionally substituted with one or more Ry substituents; “    ” represents the carbon atom or heteroatom to which the ring is attached, which is an adjacent atom pair of the carbon atom or heteroatom shared by an other ring when the ring is fused to the other ring. In one embodiment, in the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring in Ring A, the 5- or 6-membered monocyclic heterocycloalkyl ring is selected from the group consisting of: , said groups being optionally substituted with one or more Ry substituents; “ represents the carbon atom or heteroatom to which the ring is attached, which is an adjacent atom pair of the carbon atom or heteroatom shared by an other ring when the ring is fused to the other ring. In one embodiment, in the 9- or 10-membered bicyclic heteroaryl formed by fusion of a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A, the 5- or 6-membered monocyclic heteroaryl ring is selected from the group consisting of: wherein RD is hydrogen or Ry; “    ” represents two carbon atoms to which the ring is attached, which is an adjacent atom pair of the carbon atoms shared by an other ring when the ring is fused to the other ring. In one embodiment, when Ring A is a 5- or 6-membered monocyclic heteroaryl, the 5- or 6-membered monocyclic heteroaryl is selected from the group consisting of: / =N      / "“N / =N.    / =\ .s / =N              / =N N \ N n -04           Nw NC J) NC N-C N-< N , N        ,       N,N,N        ,           ,       X, said groups being optionally substituted with one or more Ry substituents; the position indicated by ” represents the point of attachment to Lx. In one embodiment, when Ring A is C6-8 aryl, the C6-8 aryl is selected from phenyl or naphthyl, said groups being optionally substituted with one or more Ry substituents. In one embodiment, Ring A is: wherein S1, S2, S3, S4, S5, S6, S7, S8 are each independently selected from CH2, CH, NH, N, O, or S; wherein said Ring A contains at least 1, 2, 3, 4, or 5 N atoms; S9, S10 are each independently selected from N or CH; q1, q2 are each independently 0, 1, or 2. In    one     embodiment,     Ring    A    is: In one embodiment, Ring B is In one embodiment, Ring B is In one embodiment, Ring B is In one embodiment, Ring B is In one embodiment, Ry is selected from: halogen, =O, hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, -NH2, -NHCH3, -N(CH3)2, -CH2-OC(O)(CH3)3, -CH2-OP(O)(OH)2, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, thienyl, N-alkylpyrrolidinonyl, furyl, morpholinyl, piperazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, naphthyl, -O-thienyl, -O-N-alkylpyrrolidinonyl, -O-furyl, -O-thiazolyl, -O-isothiazolyl, -O-imidazolyl, -O-oxazolyl, -O-pyrrolyl, -O-pyrazolyl, -O-triazolyl, -O-1,2,3-triazolyl, -O-1,2,4-triazolyl, -O-1,2,5-triazolyl, -O-1,3,4-triazolyl, -O-tetrazolyl, -O-isoxazolyl, -O-oxadiazolyl, -O-1,2,3-oxadiazolyl, -O-1,2,4-oxadiazolyl, -O-1,2,5-oxadiazolyl, -O-1,3,4-oxadiazolyl, -O-thiadiazolyl, -O-pyridyl, -O-pyridazinyl, -O-pyrimidinyl, -O-pyrazinyl, -O-phenyl; wherein said thienyl, N-alkylpyrrolidinonyl, furyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, and naphthyl are optionally substituted with one or more substituents selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, fluoromethyl, difluoromethyl, or trifluoromethyl. In one embodiment, Ry is selected from: halogen, =O, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, -NH2,  -NHCH3,  -N(CH3)2, -CH2-OC(O)(CH3)3,  -CH2-OP(O)(OH)2,   fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, thienyl, N-alkylpyrrolidinonyl, furyl, morpholinyl, piperazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, naphthyl, -O-thienyl, -O-N-alkylpyrrolidinonyl, -O-furyl, -O-thiazolyl, -O-isothiazolyl, -O-imidazolyl, -O-oxazolyl, -O-pyrrolyl, -O-pyrazolyl, -O-triazolyl, -O-1,2,3-triazolyl, -O-1,2,4-triazolyl, -O-1,2,5-triazolyl, -O-1,3,4-triazolyl, -O-tetrazolyl, -O-isoxazolyl, -O-oxadiazolyl, -O-1,2,3-oxadiazolyl, -O-1,2,4-oxadiazolyl, -O-1,2,5-oxadiazolyl, -O-1,3,4-oxadiazolyl, -O-thiadiazolyl, -O-pyridyl, -O-pyridazinyl, -O-pyrimidinyl, -O-pyrazinyl, -O-phenyl; wherein said thienyl, N-alkylpyrrolidinonyl, furyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, and naphthyl are optionally substituted with one or more substituents selected from F, Cl, Br, I, methyl, or ethyl. In one embodiment, Ry is selected from: halogen, =O, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, -NH2, -NHCH3, -N(CH3)2, fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, thienyl, N-alkylpyrrolidinonyl, furyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, naphthyl, -O-thienyl, -O-N-alkylpyrrolidinonyl, -O-furyl, -O-thiazolyl, -O-isothiazolyl, -O-imidazolyl, -O-oxazolyl, -O-pyrrolyl, -O-pyrazolyl, -O-triazolyl, -O-1,2,3-triazolyl, -O-1,2,4-triazolyl, -O-1,2,5-triazolyl, -O-1,3,4-triazolyl, -O-tetrazolyl, -O-isoxazolyl, -O-oxadiazolyl, -O-1,2,3-oxadiazolyl, -O-1,2,4-oxadiazolyl, -O-1,2,5-oxadiazolyl, -O-1,3,4-oxadiazolyl, -O-thiadiazolyl, -O-pyridyl, -O-pyridazinyl, -O-pyrimidinyl, -O-pyrazinyl, -O-phenyl; wherein said thienyl, N-alkylpyrrolidinonyl, furyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, and naphthyl are optionally substituted with one or more substituents selected from F, Cl, Br, I, methyl, or ethyl. In one embodiment, Ry is selected from: halogen, =O, hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, -NH2, -NHCH3, -N(CH3)2, -CH2-OC(O)(CH3)3,  -CH2-OP(O)(OH)2,   fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,  1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, naphthyl, -O-phenyl; wherein said imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,   1,2,5-triazolyl,   1,3,4-triazolyl,  tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl,  1,2,5-oxadiazolyl,  1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, and naphthyl are optionally substituted with one or more substituents selected from F, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, fluoromethyl, difluoromethyl, or trifluoromethyl. In one embodiment, Ry is selected from: halogen, =O, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, -NH2,  -NHCH3,  -N(CH3)2,  -CH2-OC(O)(CH3)3,  -CH2-OP(O)(OH)2, fluoromethyl, difluoromethyl, trifluoromethyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, naphthyl, -O-phenyl; wherein said imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, and naphthyl are optionally substituted with one or more substituents selected from F, Cl, Br, I, methyl, ethyl, propyl, or isopropyl. In one embodiment, Ry is selected from: halogen, =O, methyl, ethyl, isopropyl, tert-butyl, methoxy, -NH2, -NHCH3, -N(CH3)2, -CH2-OC(O)(CH3)3, -CH2-OP(O)(OH)2, fluoromethyl, difluoromethyl, trifluoromethyl, pyrazolyl, imidazolyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl, phenyl, -O-phenyl; wherein said pyrazolyl, imidazolyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl, and phenyl are optionally substituted with one or more substituents selected from F, Cl, Br, methyl, or ethyl. In one embodiment, Ry is selected from: halogen, methyl, tert-butyl, methoxy, -NH2, -NHCH3, -N(CH3)2, -CH2-OC(O)(CH3)3, -CH2-OP(O)(OH)2, difluoromethyl, trifluoromethyl, pyrazolyl, pyridyl, pyrimidinyl, phenyl, -O-phenyl; wherein said pyrazolyl, pyridyl, pyrimidinyl, and phenyl are optionally substituted with one or more substituents selected from F, Cl, or methyl. In one embodiment, Ry is selected from: halogen, hydroxyl, =O, amino, methylamino, dimethylamino, methyl, tert-butyl, trifluoromethyl, methoxy, -CH2-OC(O)(CH3)3, -CH2-OP(O)(OH)2, morpholinyl, In one embodiment, Ry is selected from: halogen, hydroxyl, amino, methyl, tert-butyl, trifluoromethyl, h T Q 'X Cl (5 Tv T) methoxy, I , '—' ,        F, '—' ,        ,     V N , N or '— / . In one embodiment, Ring A is selected from the following groups: 838883888 838 8" 38 8883 83 S S 8- 8.5 8 8 8 S.OO5QOQ0 C GOO H o o & 8 S 2 8 3" £  8. ; saivi groups being optionally substituted with one or more Ry substituents. In one embodiment, Ring A is selected from: NH HA 3 '^N / "A [A W W r\ ^n-n' U^n VJ n^3 Vnh hn^n W xU hn^n , ,,,,,,, , 382833888 ,, ,,, ,,,, 3883088888 ,,  ,,,  ,,,  ,  , groups being optionally substituted with one or more Ry substituents. g p p p p g In one embodiment, Ring A is selected from:        , '''x ,   x^ ,   \ / ,  \ /  , \ / , O p Q P Q m Ax R u O >0" N-g S^N        BBp' pj> N^p ,,,,,  ,  ,,, S Q B S 5 Q S S 6 ,,,, , ,, ,, p "g "B S S S.., . ............ '---'  ,      ''X  ,    '---'  ,    '---'  , n / , x / ; said groups being optionally substituted with one or more Ry substituents. In one embodiment, Ring A is selected from the following groups: ; said groups being optionally substituted with one or more Ry substituents. In        one        embodiment,        Ring        A        is        selected        from: 23 embodiment, Ring is selected In A one from: I                                                                                                                                                                                                                                                                                                                                                                 I I ,g- g g embodiment, Ring is selected In A one from: A         is         selected In        one        embodiment,        Ring from: In one embodiment, Ring A is In one embodiment, Rx is hydrogen, C1-6 alkoxy, -C(O)NRx1Rx2, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkoxy is optionally substituted with one or more C3-6 cycloalkyl groups; said 4- to 8-membered nitrogen-containing heterocycloalkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more substituents selected from halogen, hydroxyl, C1-6 alkyl, hydroxy-substituted C1-6 alkyl, or halogen-substituted C1-6 alkyl; said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or S as ring atoms. In one embodiment, Rx is hydrogen, C1-6 alkoxy, -C(O)NRx1Rx2, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkoxy is optionally substituted with one or more C3-6 cycloalkyl groups; said 4- to 8-membered nitrogen-containing heterocycloalkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more substituents selected from halogen, hydroxyl, C1-6 alkyl, or hydroxy-substituted C1-6 alkyl; said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or S as ring atoms. In one embodiment, Rx1, Rx2 are each independently hydrogen or methyl, ethyl, or propyl. In one embodiment, Rx1, Rx2 are each independently hydrogen or methyl. In one embodiment, Rx is hydrogen, C1-6 alkoxy, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkoxy is optionally substituted with one or more C3-6 cycloalkyl groups; said 4- to 8-membered nitrogen-containing heterocycloalkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more substituents selected from halogen, hydroxyl, C1-6 alkyl, hydroxy-substituted C1-6 alkyl, or halogen-substituted C1-6 alkyl; said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or S as ring atoms. In one embodiment, Rx is hydrogen, methoxy, ethoxy, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, optionally substituted with one or more substituents selected from halogen, hydroxyl, C1-6 alkyl, hydroxy-substituted C1-6 alkyl, or halogen-substituted C1-6 alkyl; said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or S as ring atoms. In one embodiment, Rx is methoxy, ethoxy, -C(O)N(CH3)2, -C(O)NH2, or t)...... '—' , wherein said methoxy or ethoxy is optionally substituted with one or more cyclopropyl groups, and said or are optionally substituted with one or more substituents selected from hydroxyl, F, Cl, Br, methyl, ethyl, propyl, isopropyl, hydroxymethyl, hydroxyethyl, or hydroxypropyl. In one embodiment, Rx is methoxy, -C(O)NH2, or t)......                . '—' , wherein said methoxy is optionally substituted with one or more cyclopropyl groups, and said or are optionally substituted with one or more substituents selected from hydroxyl, F, Cl, Br, or hydroxyethyl. In one embodiment, Rx is methoxy, -C(O)NH2, In one embodiment, Rx is methoxy, In one embodiment, Rx is or In one embodiment, Rx is a 4- to 8-membered nitrogen-containing heterocycloalkyl, wherein said 4- to 8-membered nitrogen-containing heterocycloalkyl contains 1 or 2 N atoms. In one embodiment, the 4- to 8-membered nitrogen-containing heterocycloalkyl is selected from: In one embodiment, Lx is selected from *-C(O)NH-**, *-CH2-NH-**, or *-NH-C(O)-**; wherein the position indicated by “*” represents the point of attachment to Ring A, and the position indicated by “**” represents the point of attachment to the group on the other side of Lx. In one embodiment, Lx is selected from *-C(O)NH-** or *-CH2-NH-**; wherein the position indicated by “*” represents the point of attachment to Ring A, and the position indicated by “**” represents the point of attachment to the group on the other side of Lx. In one embodiment, Lx is *-C(O)NH-**; wherein the position indicated by “*” represents the point of attachment to Ring A, and the position indicated by “**” represents the point of attachment to the group on the other side of Lx. In one embodiment, the compound is a compound represented by Formula (IA1) or Formula (IA2): Rx                                (IA1) Rx                                   (IA2) wherein E3, L, W1, W2, W3, W4, Rx, Lx, and Ring A are each defined as above; F1 is NRF1, O, or S; F2 is N or CRF2; F3 is N or CRF3; F4 is N or CRF4; and at least one of F1, F2, F3, F4 is N; RF1, RF2, RF3, RF4 are each independently hydrogen or R1; K1 is NRK1 or CRK2; K2 is N or CRK2; K3 is N or CRK3; K4 is N or CRK4; K5 is N or CRK5; and at least one of K1, K2, K3, K4, K5 is N; RK1, RK2, RK3, RK4, RK5 are each independently hydrogen or R1. In one embodiment, the compound is a compound represented by Formula (IA1-1) or Formula (IA2-1): Rx                                  (IA1-1) Rx                                   (IA2-1) wherein E3, L, Rx, Lx, and Ring A are each defined as above; F1 is NRF1, O, or S; F2 is N or CRF2; F3 is N or CRF3; F4 is N or CRF4; and at least one of F1, F2, F3, F4 is N; RF1, RF2, RF3, RF4 are each independently hydrogen or R1; K1 is NRK1 or CRK2; K2 is N or CRK2; K3 is N or CRK3; K4 is N or CRK4; K5 is N or CRK5; and at least one of K1, K2, K3, K4, K5 is N; RK1, RK2, RK3, RK4, RK5 are each independently hydrogen or R1. In one embodiment, the compound is a compound represented by Formula (IB1), Formula (IB2), Formula (IB3), Formula (IB4), or Formula (IB5): it                                   tz                                   it                                  it T 2 2 2 2 ><      ,___________ Qi                ><      ___________. Qi              ><       ___________ tk              x V / V     V / V     V / \V    ~ V / \V o o o o ' CO____CXI                                    X CO____CXI                                  X co____CXI                                  X co          <N / L ^z^      ^z^      ^z^ —1                                   —1                                  —I                                   —1 CO                                 CO                                00                                co LU                                   LU                                  LU                                   LU (IB1) (IB2) (IB3) (IB4) E3----L (IB5) wherein E3, L, W1, W2, W3, W4, Rx, Lx, Ry, and y are each defined as above. In one embodiment, the compound is a compound represented by Formula (IB1-1), Formula (IB2-1), Formula (IB3-1), Formula (IB4-1), or Formula (IB5-1): E3 E3 E3 R (IB1-1) Lx (IB2-1) Lx (IB3-1) E3----L (IB4-1) E3----L (IB5-1) wherein E3, L, Rx, Lx, Ry, and y are each defined as above. In one embodiment, the 4- to 12-membered nitrogen-containing heterocycloalkyl is selected from: X1, X2, X3, X4 are each independently N or -CRd; X5 is a single bond, -O-, -S-, -NRa-, or -NReRf; n1, n2, n3, n4, n5, n6 are each independently 0, 1, 2, or 3; wherein Rd, Re, Rf are each independently hydrogen, hydroxyl, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, or C3-6 cycloalkyl. In one embodiment, L is selected from: 6*—x. wherein, X1, X2, X3, X4, X11, X12, X21, X22, X31, X32, X41, X42 are each independently N or -CRd; wherein Rd is hydrogen, hydroxyl, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, or C3-6 cycloalkyl; n1, n2, n3, n4, n11, n12, n21, n22, n31, n32 are each independently 0, 1, 2, or 3; L1, L2, L3, L4 are each independently -CRL1RL2-, -NRL3-, -CRL1RL2-NRL3-, -NRL3-CRL1RL2-, or -ORL4; RL1, RL2, RL3, RL4 are each independently =O, hydrogen, halogen, C1-6 alkyl, or C1-6 haloalkyl; m1, m2, m3, m4 are each independently 0 or 1; wherein the position indicated by “    ” represents the point of attachment to E3, and the position indicated by “ ” represents the point of attachment to Ring B. In one embodiment, L is selected from: wherein, X1, X2, X3, X4, n1, n2, n3, n4 are each independently as defined above; L1, L2, L3, L4 are each independently -CRL1RL2-, -NRL3-, -CRL1RL2-NRL3-, -NRL3-CRL1RL2-, or -ORL4; RL1, RL2, RL3 are each independently =O, hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkynyl; m1, m2, m3, m4 are each independently 0 or 1; wherein the position indicated by “    ” represents the point of attachment to E3, and the position indicated by “ ” represents the point of attachment to Ring B. In one embodiment, L is selected from: ; wherein, the position indicated by “ represents the point of attachment to E3, and the position indicated by “      ” represents the point of attachment to Ring B. In one embodiment, L is selected from: , ; wherein the position , indicated by “    ” represents the point of attachment to E3, and the position indicated by “ ” represents the point of attachment to Ring B. In one embodiment, L is selected from: wherein the position indicated by “    ” represents the point of attachment to E3, and the position indicated by “ ” represents the point of attachment to Ring B. In one embodiment, L is selected from: wherein the position indicated by “    ” represents the point of attachment to E3, and the position indicated by “ represents the point of attachment to Ring B. In one embodiment, L is selected from: ; wherein the position indicated by “ represents the point of attachment to E3, and the position indicated by “ ” represents the point of attachment to Ring B. In one embodiment, E3 has a structure represented by Formula (C1), (C2), (C3), (C4), (C5), (C6), (C7), (C8), or (C9): (C2) (C1) r5 Rs (C3) (C5) (C7) (C8) (C9) wherein T1, T2, T3, T4, T5 are each independently CH, C, or N; T is CH2, CH(C1-6 alkyl), C=O, SO2, NH, or N(C1-6 alkyl); R2, R5, R6, R8, R9 are each independently hydrogen, C1-6 alkyl, or C1-6 alkoxy, wherein said C1-6 alkyl is optionally substituted with one or more substituents selected from C1-6 alkoxy or -OC(O)-C1-6 alkyl; preferably, R2, R5, R6, R8, R9 are each independently hydrogen or C1-6 alkyl; R3 is hydrogen, hydroxyl, or C1-6 alkyl; R4, R7, R10 are each independently hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, or halo-C1-6 alkyl; preferably, R4, R7, R10 are each independently hydrogen, halogen, C1-6 alkyl, or halo-C1-6 alkyl; m7, m8, m9, m10 are each independently 0, 1, 2, or 3. o, r5 m9 r5 R, m9 m9 r5-n (R?)m9 O 0 r5-n In one embodiment, E3 is o 0 H N R7 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, or halo-C1-6 alkyl; R5 is hydrogen, C1-6 alkyl, or C1-6 alkoxy, wherein said C1-6 alkyl is optionally substituted with one or more substituents selected from C1-6 alkoxy or -OC(O)-C1-6 alkyl; m9 is 1, 2, or 3. In one embodiment, E3 is ; R7 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, or halo-C1-6 alkyl; R5 is hydrogen, C1-6 alkyl, or C1-6 alkoxy, wherein said C1-6 alkyl is optionally substituted with one or more substituents selected from C1-6 alkoxy or -OC(O)-C1-6 alkyl; m9 is 1, 2, or 3. In one embodiment, E3 is or halo-C1-6 alkyl; R5 is hydrogen, C1-6 alkyl, or C1-6 alkoxy, wherein said C1-6 alkyl is optionally substituted with one or more substituents selected from C1-6 alkoxy or -OC(O)-C1-6 alkyl; m9 is 1, 2, or 3. In one embodiment, R7 is hydrogen, F, Cl, Br, methyl, methoxy, or trifluoromethyl. In one embodiment, R5 is hydrogen or -CH2-OC(O)(CH3)3. In one embodiment, E3 is In one embodiment, E3 is In one embodiment, E3 is In one embodiment, E3 is In one embodiment, E3 is In one embodiment, E3 is In one embodiment, E3 is In one embodiment, the compound is a compound from Table A, Table B, Table C, Table D, or Table E. In one embodiment, the compound is capable of degrading BTK protein and / or IRAK4 protein. In one embodiment, the compound is capable of simultaneously degrading BTK and IRAK4 proteins. In yet another aspect, the present application provides a pharmaceutical composition comprising the aforementioned compound, a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof. In yet another aspect, the present application provides the use of the aforementioned compound, a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof, or the aforementioned pharmaceutical composition, in the preparation of a medicament for treating a disorder mediated by BTK protein and / or IRAK4 protein in a patient. In yet another aspect, the present application provides the use of the aforementioned compound, a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof, or the aforementioned pharmaceutical composition, in the preparation of a BTK and / or IRAK4 degrader; preferably, said degrader is a bifunctional BTK and IRAK4 degrader. In yet another aspect, the present application provides a method for simultaneously degrading BTK and / or IRAK4 proteins in a biological sample, comprising contacting the biological sample with the aforementioned compound, a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof, or the aforementioned pharmaceutical composition. In yet another aspect, the present application provides a method for treating a disorder mediated by BTK protein and / or IRAK4 protein in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the aforementioned compound, a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof, or the aforementioned pharmaceutical composition. In one embodiment, the IRAK and / or BTK-mediated disorder is selected from: cancer, neurodegenerative disease, viral disease, autoimmune disease, inflammatory disorder, genetic disorder, hormone-related disease, metabolic disorder, condition associated with organ transplantation, immunodeficiency disorder, destructive bone lesion, proliferative disorder, infectious disease, condition associated with cell death, thrombin-induced platelet aggregation, liver disease, pathological immune condition mediated by T cell activation, cardiovascular disorder, and CNS disorder. In one embodiment, the cancer or proliferative disorder is selected from: benign or malignant tumors, solid tumors, brain cancer, kidney cancer, liver cancer, adrenal cancer, bladder cancer, breast cancer, gastric cancer, stomach tumor, ovarian cancer, colon cancer, rectal cancer, prostate cancer, pancreatic cancer, lung cancer, vaginal cancer, cervical cancer, testicular cancer, genitourinary tract cancer, esophageal cancer, laryngeal cancer, skin cancer, bone cancer or thyroid cancer, sarcoma, glioblastoma, neuroblastoma, multiple myeloma, gastrointestinal cancer, colon cancer, colorectal adenoma, tumors of the head and neck, epidermal hyperproliferation, psoriasis, prostatic hyperplasia, neoplasia, neoplasia of epithelial character, adenoma, adenocarcinoma, keratoacanthoma, epidermoid carcinoma, large cell carcinoma, non-small cell lung cancer, lymphoma, Hodgkin's or non-Hodgkin's lymphoma, mammary carcinoma, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, hematological cancers of IL-1 driven disorders, MyD88 driven disorders, multiple myeloma (including smoldering or indolent types), hematological malignancies, myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, myelodysplastic syndromes, Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma) hairy cell, mantle cell lymphoma, Waldenstrom's macroglobulinemia, marginal zone lymphoma, and follicular lymphoma; said hematological malignancy is selected from leukemia, diffuse large B-cell lymphoma (DLBCL), activated B cell-like diffuse large B-cell lymphoma (ABC DLBCL), chronic lymphocytic leukemia (CLL), chronic lymphocytic lymphoma, primary effusion lymphoma, Burkitt's lymphoma / leukemia, acute lymphocytic leukemia, B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenstrom's macroglobulinemia (WM), splenic marginal zone lymphoma, plasmacytoma, or intravascular large B-cell lymphoma. In one embodiment, the MyD88-driven disorder is selected from: ABC DLBCL, Waldenstrom's macroglobulinemia, Hodgkin's lymphoma, primary cutaneous T-cell lymphoma, and chronic lymphocytic leukemia. In one embodiment, the neurodegenerative disease is selected from: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, cerebral ischemia, and neurodegenerative diseases caused by traumatic injury, glutamate neurotoxicity, hypoxia, epilepsy, diabetes treatment, metabolic syndrome, obesity, organ transplantation, and graft-versus-host disease. In one embodiment, the inflammatory disorder is selected from the group consisting of: ocular allergy, conjunctivitis, dry eye syndrome, vernal conjunctivitis; allergic rhinitis, hemolytic anemia, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, or another inflammatory disease involving autoimmune response or having an autoimmune component or etiology, systemic lupus erythematosus, rheumatoid arthritis, polychondritis, scleroderma, Wegener's granulomatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Stevens-Johnson syndrome, idiopathic steatorrhea, ulcerative colitis, Crohn's disease or another autoimmune inflammatory bowel disease, irritable bowel syndrome, celiac disease, periodontitis, hyaline membrane disease, nephropathy, glomerular disease, alcoholic liver disease, endocrine ophthalmopathy, Graves' disease, sarcoidosis, alveolitis, chronic hypersensitivity pneumonitis, multiple sclerosis, primary biliary cirrhosis, uveitis (anterior and posterior), Sjogren's syndrome, vernal keratoconjunctivitis, interstitial pulmonary fibrosis, psoriatic arthritis, systemic juvenile idiopathic arthritis, nephritis, diverticulitis, interstitial cystitis, glomerulonephritis (with or without nephrotic syndrome, optionally including idiopathic nephrotic syndrome or minimal change nephropathy), chronic granulomatous disease, endometriosis, leptospiral nephropathy, glaucoma, retinal disease, aging, headache, pain, complex regional pain syndrome, cardiac hypertrophy, muscle atrophy, catabolic disorders, obesity, fetal growth retardation, hypercholesterolemia, heart disease, chronic heart failure, mesothelioma, anhidrotic ectodermal dysplasia, Behcet's disease, incontinentia pigmenti, Paget's disease, pancreatitis, hereditary periodic fever syndromes, asthma (allergic, non-allergic, mild, moderate, severe, bronchitic, or exercise-induced), acute lung injury, acute respiratory distress syndrome, eosinophilia, anaphylaxis, systemic anaphylaxis, sinusitis, silica-induced disease, COPD (injury, airway inflammation, bronchial hyperresponsiveness, remodeling, or reduced disease progression), pulmonary disease, cystic fibrosis, acid-induced lung injury, pulmonary hypertension, polyneuropathy, cataract, muscle inflammation with systemic sclerosis, inclusion body myositis, myasthenia gravis, thyroiditis, Addison's disease, lichen planus, type 1 diabetes, type 2 diabetes, appendicitis, atopic dermatitis, allergy, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, chronic graft rejection, colitis, conjunctivitis, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, Henoch-Schonlein purpura, hepatitis, hidradenitis suppurativa, IgA nephropathy, interstitial lung disease, laryngitis, mastitis, meningitis, myelitis, myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, phlebitis, pneumonia, polymyositis, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendinitis, tonsillitis, vaginitis, vasculitis, vulvitis, alopecia areata, erythema multiforme, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity vasculitis, urticaria, bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, epidermolysis bullosa acquisita, acute and chronic gout, chronic gouty arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, cryopyrin-associated periodic syndromes (CAPS), and osteoarthritis. In one embodiment, the autoimmune disease is selected from: urticaria, graft-versus-host disease, pemphigus vulgaris, achalasia, Addison's disease, Adult Still's disease, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM / anti-TBM nephritis, antiphospholipid syndrome, autoimmune angioedema, autoimmune familial autonomic dysfunction, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, axonal and neuronal neuropathy (AMAN), Balo disease, Behcet's disease, benign mucosal pemphigoid, bullous pemphigoid, Castleman disease (CD), celiac disease, Chagas disease, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic recurrent multifocal osteomyelitis (CRMO), allergic granulomatous angiitis (CSS) or eosinophilic granulomatosis (EGPA), cicatricial pemphigoid, Cogan's syndrome, cold agglutinin disease, congenital heart block, coxsackie myocarditis, CREST syndrome, Crohn's disease, dermatitis herpetiformis, dermatomyositis, Devic's disease (neuromyelitis optica), discoid lupus, Dressler's syndrome, endometriosis, eosinophilic esophagitis (EoE), eosinophilic fasciitis, erythema nodosum, mixed cryoglobulinemia, Evans syndrome, fibromyalgia, fibrosing alveolitis, giant cell arteritis (temporal arteritis), giant cell myocarditis, glomerulonephritis, Goodpasture's syndrome, granulomatosis with polyangiitis, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, hemolytic anemia, Henoch-Schonlein purpura (HSP), herpes gestationis or pemphigoid gestationis (PG), hidradenitis suppurativa (HS) (acne inversa), hypogammaglobulinemia, IgA nephropathy, IgG4-related sclerosing disease, immune thrombocytopenic purpura (ITP), inclusion body myositis (IBM), interstitial cystitis (IC), juvenile arthritis, juvenile diabetes (type 1 diabetes), juvenile myositis (JM), Kawasaki disease, Lambert-Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus et atrophicus, ligneous conjunctivitis, linear IgA disease (LAD), lupus, chronic Lyme disease, Meniere's disease, microscopic polyangiitis (MPA), mixed connective tissue disease (MCTD), Mooren's ulcer, Mucha-Habermann disease, multifocal motor neuropathy (MMN) or MMNCB, multiple sclerosis, myasthenia gravis, myositis, narcolepsy, neonatal lupus, neuromyelitis optica, neutropenia, ocular cicatricial pemphigoid, optic neuritis, palindromic rheumatism (PR), PANDAS, paraneoplastic cerebellar degeneration (PCD), paroxysmal nocturnal hemoglobinuria (PNH), Parry-Romberg syndrome, pars planitis (peripheral uveitis), Parsonage-Turner syndrome, pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia (PA), POEMS syndrome, polyarteritis nodosa, polyglandular syndromes type I, II, III, polymyalgia rheumatica, polymyositis, post-myocardial infarction syndrome, post-pericardiotomy syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, progesterone dermatitis, psoriasis, psoriatic arthritis, pure red cell aplasia (PRCA), pyoderma gangrenosum, Raynaud's phenomenon, reactive arthritis, reflex sympathetic dystrophy, relapsing polychondritis, restless legs syndrome (RLS), retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis, scleroderma, Sjogren's syndrome, sperm and testicular autoimmune disease, stiff person syndrome (SPS), subacute bacterial endocarditis (SBE), Susac's syndrome, sympathetic ophthalmia (SO), Takayasu's arteritis, temporal arteritis (giant cell arteritis), thrombotic thrombocytopenic purpura (TTP), Tolosa-Hunt syndrome (THS), transverse myelitis, type 1 diabetes, ulcerative colitis (UC), undifferentiated connective tissue disease (UCTD), uveitis, vasculitis, vitiligo, Vogt-Koyanagi-Harada disease, and Wegener's granulomatosis (or granulomatosis with polyangiitis (GPA)). BRIEF DESCRIPTION OF THE FIGURES Figure 1 shows the degradation activity of compounds of the present application against BTK and IRAK4 in TMD8 cells at various concentrations, as measured in Test Example 3, with an incubation time of 16 hours. DETAIL DESCRIPTION OF THE INVENTION I. DEFINITIONS In the present application, unless otherwise stated, scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, the relevant terms and laboratory operation procedures used herein are terms and routine procedures widely used in the corresponding fields. Meanwhile, for a better understanding of the present application, definitions and explanations of relevant terms are provided below. As used herein and unless otherwise specified, the term “about” or “approximately” means within plus or minus 10% of a given value or range. Where integers are required, the term means within plus or minus 10% of a given value or range, rounded up or down to the nearest integer. In the description herein, references to “some examples,” “some embodiments,” or “some implementations” describe a subset of all possible embodiments, but it is understood that “some embodiments” may be the same or different subsets of all possible embodiments, and may be combined with each other without conflict. As used herein and unless otherwise specified, the terms “comprising,” “including,” “having,” “containing,” including their grammatical equivalents, shall generally be understood as open-ended and non-limiting, for example, not excluding other unlisted elements or steps. As used herein, the term “heteroatom” is selected from nitrogen, oxygen, or sulfur, wherein nitrogen may be optionally substituted; sulfur may also be optionally substituted, for example by oxo, i.e., forming S(O)t3 (where t3 is an integer from 0 to 2). As used herein, when a group such as alkyl is located in the middle of a structural formula, the group is a divalent radical. For example, alkyl is alkylene, etc. As used herein, the term “alkyl” refers to a chain (straight or branched) saturated aliphatic hydrocarbon group. The term “alkyl” may be a straight or branched chain alkyl group containing 1 to 20 carbon atoms (C1-20 alkyl), preferably an alkyl group containing 1 to 12 carbon atoms (C1-12 alkyl). Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl,   3-methylbutyl,   n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl,   3,3-dimethylpentyl,   2-ethylpentyl,   3-ethylpentyl,   n-octyl,   2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, and various branched isomers thereof. More preferred are lower alkyl groups containing 1 to 6 carbon atoms (C1-6 alkyl), non-limiting examples including methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl,   1,1-dimethylpropyl, 1,2-dimethylpropyl,  2,2-dimethylpropyl,   1-ethylpropyl,  2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, etc. Lower alkyl groups containing 1 to 3 carbon atoms (C1-3 alkyl), non-limiting examples including methyl, ethyl, n-propyl, isopropyl, etc are more preferred. Alkyl groups may be substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the groups described herein. As used herein, the term “alkynyl” refers to a straight or branched aliphatic hydrocarbon group containing at least one C=C triple bond. The triple bond may be located at any possible position of the hydrocarbon chain. As used herein, the term “C2-6 alkynyl” refers to an alkynyl group containing 2 to 6 carbon atoms, such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, etc. Alkynyl groups may be optionally substituted with one or more suitable substituents. As used herein, the terms “cycloalkyl” and “cycloalkyl ring” are used interchangeably and refer to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon group. The term “cycloalkyl” may be a cycloalkyl group containing 3 to 20 carbon atoms (C3-20 cycloalkyl), typically containing 3 to 6 carbon atoms (C3-6 cycloalkyl) for a monocyclic cycloalkyl (C3-6 monocyclic cycloalkyl). As used herein, “3-to 6-membered monocyclic,” “3- to 6-membered monocyclic cycloalkyl,” “C3-6 monocyclic cycloalkyl,” and “C3-6 cycloalkyl” are used interchangeably and refer to a saturated or partially unsaturated all-carbon monocyclic ring containing 3 to 6 ring atoms. The ring carbon atoms of said monocyclic ring may be optionally substituted with 1, 2, or 3 oxo groups to form a cyclic ketone structure. Examples of 3- to 6-membered monocyclic rings include (but are not limited to): cyclopropyl ring, cyclobutyl ring, cyclopentyl ring, cyclopentenyl ring, cyclohexyl ring, cyclohexenyl ring, cyclohexadienyl ring, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, cyclohexane-1,3-dione, etc. As used herein, the terms “heterocycloalkyl” and “heterocycloalkyl ring” are used interchangeably and refer to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon group, wherein one or more (preferably 1 to 4, or 1 to 3, or 1 to 2) ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)t3 (where t3 is an integer from 0 to 2), excluding ring moieties of -O-O-, -O-S-, or -S-S-, with the remaining ring atoms being carbon. The term "heterocycloalkyl" may be a heterocycloalkyl group containing 3 to 20 ring atoms (i.e., 3- to 20-membered); preferably 3- to 12-membered heterocycloalkyl; more preferably 3-to 10-membered heterocycloalkyl; even more preferably 3- to 6-membered heterocycloalkyl; wherein one or more (preferably 1 to 4) ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)t3 (where t3 is an integer from 0 to 2), excluding ring moieties of -O-O-, -O-S-, or -S-S-, with the remaining ring atoms being carbon. Nitrogen atoms may be substituted or unsubstituted (i.e., N or NR, where R is hydrogen or any substituent as defined herein). The ring carbon atoms of said heterocycloalkyl may be optionally substituted with 1, 2, or 3 oxo groups to form a cyclic ketone, cyclic lactone, or cyclic lactam structure. In some embodiments of the present application, “heterocycloalkyl” refers to a monocyclic heterocycloalkyl, which is saturated or partially unsaturated, preferably containing 3 to 8 ring atoms (i.e., 3- to 8-membered), wherein 1, 2, or 3 are heteroatoms, more preferably containing 3 to 6 ring atoms (i.e., 3- to 6-membered), wherein 1, 2, or 3 are heteroatoms, most preferably containing 5 or 6 ring atoms (i.e., 5- or 6-membered), wherein 1, 2, or 3 are heteroatoms. As used herein, the term “3- to 6-membered heterocycloalkyl” is used interchangeably with “3- to 6-membered monocyclic heterocycloalkyl,” and the term “5- or 6-membered heterocycloalkyl” is used interchangeably with “5- or 6-membered monocyclic heterocycloalkyl.” When the heteroatom is nitrogen, the nitrogen atom may be substituted or unsubstituted (i.e., N or NR, where R is hydrogen or other substituents as defined herein). When the heteroatom is sulfur, the sulfur atom may be optionally oxidized (i.e., S(O)t3, where t3 is an integer from 0 to 2). The ring carbon atoms of said monocyclic heterocycloalkyl may be optionally substituted with 1, 2, or 3 oxo groups to form a cyclic ketone, cyclic lactone, or cyclic lactam structure. Non-limiting examples of monocyclic heterocycloalkyl include: aziridine, oxirane, azetidine, azetidin-2-one, oxetane, oxetan-2-one, oxazolidine, pyrrolidin-2-one, pyrrolidine-2,5-dione, 1,3-dioxolane, dihydrofuran-2(3H)-one, dihydrofuran-2,5-dione, piperidin-2-one, piperidine-2,6-dione, tetrahydro-2H-pyran-2-one,   imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolan-2-one, oxazolidin-2-one, imidazolidin-2-one, piperidine, piperazine, piperazin-2-one, morpholine, morpholin-3-one,      morpholin-2-one,      thiomorpholin-3-one      1,1-dioxide,      thiomorpholine, thiomorpholine-1,1-dioxide,        tetrahydropyran,        1,2-dihydroazetidine,        1,2-dihydrooxetene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3-dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4-tetrahydropyridine,      3,6-dihydro-2H-pyran,       1,2,3,6-tetrahydropyridine,       1,3-oxazinane, hexahydropyrimidine,         1,4-dioxane,        tetrahydropyrimidin-2(1H)-one,        1,4-dioxan-2-one, 5,6-dihydro-2H-pyran-2-one,        5,6-dihydropyrimidin-4(3H)-one,        3,4-dihydropyridin-2(1H)-one, 5,6-dihydropyridin-2(1H)-one, 5,6-dihydropyrimidin-4(1H)-one, pyrimidin-4(3H)-one, pyrimidin-4(1H)-one, 4,5-dihydro-1H-imidazole, 2,3-dihydro-1H-imidazole, 2,3-dihydrooxazole, 1,3-dioxole, 2,3-dihydrothiophene, 2,5-dihydrothiophene,      3,4-dihydro-2H-1,4-oxazine,      3,4-dihydro-2H-1,4-thiazine       1,1-dioxide, 1,2,3,4-tetrahydropyrazine, 1,3-dihydro-2H-pyrrol-2-one, 1,5-dihydro-2H-pyrrol-2-one, 1H-pyrrole-2,5-dione, furan-2(3H)-one, furan-2(5H)-one, 1,3-dioxol-2-one, oxazol-2(3H)-one, 1,3-dihydro-2H-imidazol-2-one, furan-2,5-dione, 3,6-dihydropyridin-2(1H)-one, pyridine-2,6(1H,3H)-dione, 5,6-dihydro-2H-pyran-2-one, 3,6-dihydro-2H-pyran-2-one,            3,4-dihydro-2H-1,3-oxazine,            3,6-dihydro-2H-1,3-oxazine, 1,2,3,4-tetrahydropyrimidine, etc. In one embodiment of the present application, non-limiting examples of the 5- or 6-membered HN-"\ HN'A r NH 1 0 monocyclic heterocycloalkyl include:             ,          , H       H H H           / N\ 0 Q A   h ,,,  ,,  , 000 oY HnA HnA     J / =0 A., / I 0      1   0      1 NH                    0 N L-^y    ky    <y    0 U         H ,,    ,     , H            H H     / N^O 0. _N. r y Y k hny YY 0^    u A  Y 0 0 0          H      H       H ,  ,  ,,, 0      0      0 Ah Ah Ah      rNY° r V      kA kA hnxA hn ,,,,  , kA kA kA O H     H     O     O     S     S     H ,,,,,,, H A / 3 r> z>° n N              n^N     y^O H °H°H°H  0 U C ,,,  ,, 1 O          L / L / N H     O     S    H ,,,,, ° H ° H     O ° ,,  ,, H 1   kA   Z\   °^vNy O^N^O k Y   kA H      0^0     0 ,    ,,, / 0   HN'^ / 0^0   y\ x J cYiA L J Y J 0   HO  0^0 ,,,, -N^°  HN-"\    HN""\  0""\ ^A A / NH Y° A / ° ,                                  ,                         ,                         , H H N 0 0 0 A A H     0' 0' 0   °''fe ,,,, , 000 \ / oY hnA hnA Ls-y0 Uyo A / NH ,,,    , Two ring atoms attached to the above monocyclic heterocycloalkyl, including C-C and N-C, may optionally be fused with a 5- or 6-membered monocyclic heteroaryl ring as defined in the present application to form a fused polycyclic ring. In some embodiments of the present application, “heterocycloalkyl” refers to a polycyclic heterocycloalkyl, including spiroheterocycloalkyl, fused heterocycloalkyl, and bridged heterocycloalkyl. As used herein, the term “spiroheterocycloalkyl” refers to a saturated or partially unsaturated polycyclic heterocycloalkyl group in which the monocyclic rings share one atom (called the spiro atom) in the ring system, wherein one or more (for example, 1 to 4, or 1 to 3, or 1 to 2) ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)t4 (where t4 is an integer from 0 to 2), with the remaining ring atoms being carbon. The term “saturated spiroheterocycloalkyl” means that the spiroheterocycloalkyl ring system has no unsaturated bonds. The term “partially unsaturated spiroheterocycloalkyl” means that one or more rings in the spiroheterocycloalkyl ring system may contain one or more double bonds, but no ring has a fully conjugated n-electron system. The term “spiroheterocycloalkyl” may be a spiroheterocycloalkyl containing 5 to 20 ring atoms (i.e., 5- to 20-membered), wherein 3- to 8-membered (i.e. containing 3-8 ring atoms) monocyclic rings share one atom (called the spiro atom), preferably 6- to 14-membered spiroheterocycloalkyl, more preferably 7- to 11-membered spiroheterocycloalkyl; wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)t4 (where t4 is an integer from 0 to 2), with the remaining ring atoms being carbon. When the heteroatom is nitrogen, the nitrogen atom may be substituted or unsubstituted (i.e., N or NR, where R is hydrogen or other substituents as defined herein). Each monocyclic ring may contain one or more double bonds, but no ring has a fully conjugated n-electron system. Based on the number of spiro atoms shared between rings, spiroheterocycloalkyl can be divided into monospiroheterocycloalkyl, dispiroheterocycloalkyl, or polyspiroheterocycloalkyl, preferably monospiroheterocycloalkyl and dispiroheterocycloalkyl. More preferred are 7-membered (4-membered / 4-membered), 8-membered (4-membered / 5-membered), 9-membered (4-membered / 6-membered,  5-membered / 5-membered), 10-membered (5-membered / 6-membered), or 11-membered   (6-membered / 6-membered)   monospiroheterocycloalkyl.   Non-limiting   examples of spiroheterocycloalkyl include: As used herein, the term “fused heterocycloalkyl” refers to a saturated or partially unsaturated polycyclic heterocycloalkyl group in which each ring in the ring system shares an adjacent pair of atoms with another ring in the ring system, and wherein one or more (for example, 1 to 4, or 1 to 3, or 1 to 2) ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)t4 (where t4 is an integer from 0 to 2), with the remaining ring atoms being carbon. The term “saturated fused heterocycloalkyl” means that the fused heterocycloalkyl ring system has no unsaturated bonds. The term “partially unsaturated fused heterocycloalkyl” means that one or more rings in the fused heterocycloalkyl ring system may contain one or more double bonds, but no ring has a fully conjugated n-electron system. The term “fused heterocycloalkyl” may be a fused heterocycloalkyl containing 5 to 20 ring atoms (i.e., 5- to 20-membered), preferably 6- to 14-membered fused heterocycloalkyl, more preferably 6- to 10-membered fused heterocycloalkyl, even more preferably 8- to 10-membered fused heterocycloalkyl; wherein one or more ring atoms in the ring system are heteroatoms selected from nitrogen, oxygen, or S(O)t4 (where t4 is an integer from 0 to 2), with the remaining ring atoms being carbon. When the heteroatom is nitrogen, the nitrogen atom may be substituted or unsubstituted (i.e., N or NR, where R is hydrogen or other substituents as defined herein). Based on the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic, or polycyclic fused heterocycloalkyl, preferably bicyclic or tricyclic, more preferably 8-membered (5-membered / 5-membered fused), 9-membered (5-membered / 6-membered fused), or 10-membered (6-membered / 6-membered fused) bicyclic fused heterocycloalkyl. Non-limiting examples of As used herein, the term “bridged heterocycloalkyl” refers to a saturated or partially unsaturated polycyclic heterocycloalkyl group in which any two rings share two atoms that are not directly connected, wherein one or more (for example, 1 to 4, or 1 to 3, or 1 to 2) ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)t3 (where t3 is an integer from 0 to 2), with the remaining ring atoms being carbon. The term “saturated bridged heterocycloalkyl” means that the bridged heterocycloalkyl ring system has no unsaturated bonds. The term “partially unsaturated bridged heterocycloalkyl” means that one or more rings in the bridged heterocycloalkyl ring system may contain one or more double bonds, but no ring has a fully conjugated n-electron system. The term “bridged heterocycloalkyl” may be a bridged heterocycloalkyl containing 5 to 20 ring atoms (i.e., 5- to 20-membered), preferably 6- to 14-membered bridged heterocycloalkyl, more preferably 7- to 10-membered bridged heterocycloalkyl; wherein one or more (for example, 1 to 4, or 1 to 3, or 1 to 2) ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)t3 (where t3 is an integer from 0 to 2), with the remaining ring atoms being carbon. Based on the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic, or polycyclic bridged heterocycloalkyl, preferably bicyclic, tricyclic, or tetracyclic, more preferably bicyclic or tricyclic. Non-limiting examples of bridged                                      heterocycloalkyl                                      include: or In the present application, the various types of heterocycloalkyl groups described above may be optionally substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the groups described herein. As used herein, in “spiroheterocycloalkyl,” “bridged heterocycloalkyl,” or “fused heterocycloalkyl,” when the ring containing the heteroatom is a 3-membered ring and contains only 1 heteroatom as a ring atom, said heteroatom is not nitrogen. As used herein, the terms “aryl,” “aryl ring,” and “aromatic ring” are used interchangeably and refer to a fully unsaturated aliphatic hydrocarbon group. It may be an all-carbon monocyclic, all-carbon polycyclic (rings connected by covalent bonds, not fused), or all-carbon fused polycyclic (i.e., rings sharing adjacent carbon atom pairs) group containing 6 to 14 ring atoms (i.e., 6- to 14-membered or C6-14), wherein at least one ring in the ring system is aromatic, i.e., has a conjugated n-electron system. Preferred are aryl groups containing 6 to 10 ring atoms (i.e., 6- to 10-membered or C6-10). Each ring in the ring system contains 5 or 6 ring atoms. In some embodiments of the present application, “aryl” refers to a monoaryl or polyaryl ring, non-limiting examples of which include: phenyl, biphenyl, etc. In some embodiments of the present application, “aryl” refers to an aromatic fused polycyclic ring, which is a polycyclic group formed by fusion of a monoaryl ring with one or more monoaryl rings, non-limiting examples of which include: naphthyl, anthryl, etc. In some embodiments of the present application, the aryl ring described herein (e.g., monoaryl ring, preferably phenyl) may be fused with one or more non-aromatic rings to form a polycyclic group, wherein the ring attached to the parent structure is an aromatic or non-aromatic ring. Said non-aromatic rings include but are not limited to: 3- to 6-membered monocyclic heterocycloalkyl rings, preferably 5- or 6-membered monocyclic heterocycloalkyl rings (wherein the ring carbon atoms of said monocyclic heterocycloalkyl ring may be substituted with 1 to 2 oxo groups to form a cyclic lactam or cyclic lactone structure); 3- to 6-membered monocyclic cycloalkyl rings, preferably 5- or 6-membered monocyclic cycloalkyl rings (wherein the ring carbon atoms of said monocyclic cycloalkyl ring may be substituted with 1 or 2 oxo groups to form a cyclic ketone structure), etc. The polycyclic group formed by fusion of the above monoaryl ring with one or more non-aromatic rings may be attached to other groups or the parent structure through a nitrogen atom or carbon atom, and the ring attached to the parent structure is a monoaryl ring or a non-aromatic ring. Herein, the fusion of a phenyl group with a 5- or 6-membered monocyclic heterocycloalkyl ring to form a 9- or 10-membered bicyclic ring means that two adjacent substituent groups on the phenyl ring together with the ring atoms to which they are attached form a fused 5- or 6-membered monocyclic heterocycloalkyl ring, as defined herein, and the resulting 9- or 10-membered bicyclic ring may also be referred to as a 9- or 10-membered phenyl-heterocycloalkyl ring. Herein, the fusion of a phenyl group with a 5- or 6-membered monocyclic cycloalkyl ring to form a 9- or 10-membered bicyclic ring means that two adjacent substituent groups on the phenyl ring together with the ring atoms to which they are attached form a fused 5- or 6-membered monocyclic cycloalkyl ring, as defined herein, and the resulting 9- or 10-membered bicyclic ring may also be referred to as a 9- or 10-membered phenyl-cycloalkyl ring. In the present application, the various types of aryl groups described above may be substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the groups described herein. As used herein, the terms “heteroaryl,” “heteroaryl ring,” and “heteroaromatic ring” are used interchangeably and refer to a fully unsaturated aliphatic hydrocarbon group containing heteroatoms. It may be a monocyclic or fused polycyclic (i.e., sharing adjacent carbon or heteroatom pairs) group having 5 to 14 ring atoms (i.e., 5- to 14-membered), preferably 5 to 10 ring atoms (i.e., 5- to 10-membered), more preferably 5, 6, 8, 9, or 10 ring atoms, containing 1 to 4 heteroatoms as ring atoms, selected from oxygen, sulfur, and nitrogen. Nitrogen and sulfur atoms may be optionally oxidized, and nitrogen atoms may be optionally quaternized. Said heteroaryl preferably has 6, 10, or 14 n electrons shared in the ring system. At least one ring in the ring system is aromatic. In some embodiments of the present application, “heteroaryl” refers to a monocyclic heteroaryl ring (preferably a 5- or 6-membered monocyclic heteroaryl ring), non-limiting examples of which include: thiophene, N-alkylpyrrolidinone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, etc. In some embodiments of the present application, “heteroaryl” refers to a fused polyheteroaryl ring (preferably an 8- to 10-membered bicyclic heteroaryl ring). Said fused polyheteroaryl ring includes both polycyclic groups formed by fusion of a monoaryl ring (preferably phenyl) with a monocyclic heteroaryl ring (preferably a 5- or 6-membered monocyclic heteroaryl ring) (preferably a 9- or 10-membered bicyclic heteroaryl ring), and polycyclic groups formed by fusion of a monocyclic heteroaryl (preferably a 5- or 6-membered monocyclic heteroaryl) with a monocyclic heteroaryl (preferably a 5- or 6-membered monocyclic heteroaryl) (preferably an 8- to 10-membered bicyclic heteroaryl ring). In some embodiments of the present application, non-limiting examples of monocyclic heteroaryl rings (preferably 5- or 6-membered monocyclic heteroaryl rings) that form fused polycyclic rings include: Non-limiting examples of fused polyheteroaryl rings include: benzo[d]isoxazole, 1H-indole, isoindole, 1H-benzo[d]imidazole, benzo[d]isothiazole, 1H-benzo[d][1,2,3]triazole, benzo[d]oxazole, benzo[d]thiazole, indazole, benzofuran, benzo[b]thiophene, quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline, pyrido[3,2-d]pyrimidine, pyrido[2,3-d]pyrimidine,   pyrido[3,4-d]pyrimidine,   pyrido[4,3-d]pyrimidine, 1,8-naphthyridine, 1,7-naphthyridine, 1,6-naphthyridine, 1,5-naphthyridine, pyrazolo[1,5-a]pyrimidine, imidazo[1,2-b]pyridazine, etc. In some embodiments of the present application, the heteroaryl ring described herein (e.g., a monocyclic heteroaryl ring, preferably a 5- or 6-membered monocyclic heteroaryl ring) may be fused with one or more non-aromatic rings to form a polycyclic group, wherein the ring attached to the parent structure is a heteroaryl ring or a non-aromatic ring. Said non-aromatic rings include but are not limited to: 3- to 6-membered (preferably 5- or 6-membered) monocyclic heterocycloalkyl rings (wherein the ring carbon atoms of said monocyclic heterocycloalkyl ring may be substituted with 1 to 2 oxo groups to form a cyclic lactam or cyclic lactone structure); 3- to 6-membered (preferably 5- or 6-membered) monocyclic cycloalkyl rings (wherein the ring carbon atoms of said monocyclic cycloalkyl ring may be substituted with 1 or 2 oxo groups to form a cyclic ketone structure), etc. The polycyclic group formed by fusion of the above monocyclic heteroaryl ring with one or more non-aromatic rings may be attached to other groups or the parent structure through a nitrogen atom or carbon atom, and the ring attached to the parent structure is a heteroaryl ring or a non-aromatic ring. Herein, the fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring to form an 8- to 10-membered bicyclic heterocyclic ring means that two adjacent substituent groups on the 5- or 6-membered monocyclic heteroaryl ring together with the ring atoms to which they are attached form a fused 5- or 6-membered monocyclic heterocycloalkyl ring, as defined herein, and the resulting 8- to 10-membered bicyclic heterocyclic ring may also be referred to as an 8- to 10-membered heteroaryl-heterocycloalkyl ring. Herein, the fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic cycloalkyl ring to form an 8- to 10-membered bicyclic heterocyclic ring means that two adjacent substituent groups on the 5- or 6-membered monocyclic heteroaryl ring together with the ring atoms to which they are attached form a fused 5- or 6-membered monocyclic cycloalkyl ring, as defined herein, and the resulting 8- to 10-membered bicyclic heterocyclic ring may also be referred to as an 8- to 10-membered heteroaryl-cycloalkyl ring. In the present application, the various types of heteroaryl groups described above may be substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the groups described herein. As used herein, the term “C1-6 alkoxy” refers to -O-(C1-6 alkyl), wherein alkyl is as defined above. Preferred is C1-3 alkoxy. Non-limiting examples include methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, isobutoxy, pentyloxy, etc. Alkoxy groups may be optionally substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the groups described herein. As used herein, “deuterated” means that one or more (e.g., 1, 2, 3, 4, or 5) or all hydrogen atoms in a group are replaced by deuterium atoms. For example, “deuterated C1-6 alkyl” means that one or more (e.g., 1, 2, 3, 4, or 5) or all hydrogen atoms in an alkyl group are replaced by deuterium atoms, wherein alkyl is as defined above. Preferred is deuterated C1-3 alkyl. For example, deuterated methyl may be monodeuterated methyl, dideuterated methyl, or perdeuterated methyl. As used herein, “halo” means that one or more (e.g., 1, 2, 3, 4, or 5) hydrogen atoms in a group are replaced by halogen. For example, “halo C1-6 alkyl” means that an alkyl group is substituted with one or more (e.g., 1, 2, 3, 4, or 5) halogen atoms, wherein alkyl is as defined above. Halo C1-3 alkyl is preferred. Examples of halo C1-6 alkyl include (but are not limited to) monochloromethyl, dichloromethyl, trichloromethyl, monochloroethyl, 1,2-dichloroethyl, trichloroethyl, monobromoethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, etc. For another example, “halo C1-6 alkoxy” means that an alkoxy group is substituted with one or more (e.g., 1, 2, 3, 4, or 5) halogens, wherein alkoxy is as defined above. Halo C1-3 alkoxy is preferred. Examples include (but are not limited to) trifluoromethoxy, trifluoroethoxy, monofluoromethoxy, monofluoroethoxy, difluoromethoxy, difluoroethoxy, etc. As used herein, the term “hydroxyl” refers to -OH. Herein, the wavy line “^ ” shown on a group, regardless of the form in which it appears, indicates the point of attachment to the rest of the molecule. If no wavy line is indicated on a group, it means that any position in the group may be attached to the rest of the molecule. The chemical bond “  ” shown on a ring indicates that the chemical bond can be attached to any ring atom on the ring, for example, includes \    , etc. The term “optional” or “optionally” means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs and instances where it does not. For example, “heterocycloalkyl optionally substituted with alkyl” means that alkyl may but need not be present, and the description includes instances where the heterocycloalkyl group is substituted with alkyl and instances where the heterocycloalkyl group is not substituted with alkyl. “Substituted” means that one or more hydrogen atoms in a group, preferably up to 5, more preferably 1 to 3 hydrogen atoms, are independently replaced by a corresponding number of substituents. It goes without saying that substituents are only at their possible chemical positions, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without undue effort. For example, an amino or hydroxyl group with a free hydrogen may be unstable when bonded to a carbon atom with an unsaturated (e.g., olefinic) bond. Unless otherwise defined, when a group described in the present application is substituted with a substituent, it means that all occurrences of the same group in the present application may be substituted with the substituent, i.e., it means that the group may be substituted when present alone, and may also be substituted when present in combination with other groups. For example, R is -C1-6 alkyl, C6-10 aryl, C3-6 monocyclic cycloalkyl, -C(O)C1-6 alkyl, -C1-4 alkyl-C6-10 aryl, or -S(O)2-C3-6 monocyclic cycloalkyl, wherein said C1-6 alkyl, C6-10 aryl, and C3-6 monocyclic cycloalkyl are optionally substituted; this description also includes that the C1-6 alkyl, C6-10 aryl, and C3-6 monocyclic cycloalkyl in -C(O)C1-6 alkyl, -C1-4 alkyl-C6-10 aryl, and -S(O)2-C3-6 monocyclic cycloalkyl are optionally substituted. Unless otherwise defined, “...... are the same or different, and each independently is ...” in the present application means that when there is more than one identical substituent group in a formula, the groups may be the same or different, and are each independently selected. For example, L is (CRL1RL2)s, and when s is 2, i.e., L is (CRL1RL2)-(CRL1RL2), the two RL1 or RL2 groups may be the same or different, and are each independently selected, for example, L may be C(CH3)(CN)-C(CH2CH3)(OH), C(CH3)(CN)-C(CH3)(OH), or C(CN)(CH2CH3)-C(OH)(CH2CH3). Unless otherwise defined, “each independently selected from ... substituents” in the present application means that when more than one hydrogen atom on a group is substituted with substituents, the substituents may be the same or different, and the selected substituents are each independently selected. In the present context, C1-6 may preferably be C1-4; more preferably C1-3. In one embodiment of the present application, in any group, said C3-6 cycloalkyl is selected from: cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. In one embodiment of the present application, in any group, said 5- or 6-membered monocyclic heteroaryl is selected from: thiophene, N-alkylpyrrolidinone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine. In one embodiment of the present application, in any group, said 5- or 6-membered monocyclic heteroaryl N— .   000^« n^n b b B is selected from: NH , ° , S , NH , S , NH , NH , S , H , 0 In one embodiment of the present application, in any group, said 8- to 10-membered bicyclic heteroaryl is selected from: benzoxazole, benzisoxazole, benzimidazole, benzothiazole, benzisothiazole, benzotriazole, benzofuran, benzothiophene, indole, indazole, isoindole, quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline, pyridopyrimidine, naphthyridine. “Pharmaceutical composition” means a mixture containing one or more of the compounds described herein or physiologically / pharmaceutically acceptable salts or prodrugs thereof with other chemical components, as well as other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to an organism, facilitate absorption of the active ingredient, and thereby exert biological activity. “Pharmaceutically acceptable salts” include pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. “Pharmaceutically acceptable acid addition salts” refers to salts formed with inorganic or organic acids that retain the biological effectiveness of the free base without other side effects. “Pharmaceutically acceptable base addition salts” include but are not limited to salts of inorganic bases such as sodium salts, potassium salts, calcium salts, magnesium salts, etc. Include but are not limited to salts of organic bases such as ammonium salts, triethylamine salts, lysine salts, arginine salts, etc. “Solvate” mentioned in the present application refers to a complex formed by a compound of the present application with a solvent. They are either reacted in a solvent or precipitated or crystallized from a solvent. For example, a complex formed with water is called a “hydrate.” Solvates of the compounds of Formula (I) of the present application are within the scope of the present application. The compounds of Formula (I) of the present application may contain one or more chiral centers and exist in different optically active forms. When a compound contains one chiral center, the compound comprises enantiomers. The present application includes both isomers and mixtures of isomers, such as racemic mixtures. Enantiomers can be resolved by methods known in the art, such as crystallization and chiral chromatography. When the compounds of Formula (I) contain more than one chiral center, diastereomers may exist. The present application includes resolved optically pure specific isomers as well as mixtures of diastereomers. Diastereomers can be resolved by methods known in the art, such as crystallization and preparative chromatography. “Stereoisomers” of the present application include (but are not limited to) enantiomers, diastereomers, etc. The present application includes prodrugs of the above compounds. Prodrugs include known amino protecting groups and carboxyl protecting groups, which are hydrolyzed under physiological conditions or released via enzymatic reactions to yield the parent compound. Specific methods for preparing prodrug can be found in (Saulnier, M.G.; Frennesson, D.B.; Deshpande, M.S.; Hansel, S.B and Vysa, D.M. Bioorg. Med. Chem. Lett. 1994, 4, 1985-1990; and Greenwald, R.B.; Choe, Y.H.; Conover, C.D.; Shum, K.; Wu, D.; Royzen, M. J. Med. Chem. 2000, 43, 475.) Generally, the compounds of the present application, their stereoisomers, N-oxides, deuterated derivatives, pharmaceutically acceptable salts, or prodrugs thereof can be formulated with one or more pharmaceutical carriers into suitable dosage forms for administration. These dosage forms are suitable for oral, rectal, topical, buccal, and other parenteral administration (e.g., subcutaneous, intramuscular, intravenous, etc.). For example, dosage forms suitable for oral administration include capsules, tablets, granules, syrups, etc. The compounds of the present application contained in these formulations may be in the form of solid powders or granules; solutions or suspensions in aqueous or non-aqueous liquids; water-in-oil or oil-in-water emulsions, etc. The above dosage forms can be prepared from the active compound with one or more carriers or excipients by general pharmaceutical methods. The above carriers need to be compatible with the active compound or other excipients. For solid preparations, commonly used non-toxic carriers include but are not limited to mannitol, lactose, starch, magnesium stearate, cellulose, glucose, sucrose, etc. Carriers for liquid preparations include water, physiological saline, aqueous glucose solutions, glycols, polyethylene glycols, etc. The active compound can form solutions or suspensions with the above carriers. The compositions of the present application are formulated, dosed, and administered in a manner consistent with good medical practice. The administration of “therapeutically effective amount” of a compound is determined by factors such as the specific condition to be treated, the individual being treated, the cause of the condition, the target of the drug, and the mode of administration. As used herein, “therapeutically effective amount” refers to an amount of a compound of the present application that will elicit a biological or medical response in an individual, for example, reducing or inhibiting enzyme or protein activity, or ameliorating symptoms, alleviating conditions, slowing or delaying disease progression, or preventing disease, etc. The therapeutically effective amount of the compound of the present application or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof comprised in the pharmaceutical composition of the present application is preferably 0.1 mg to 5 g / kg (body weight). As used herein, “pharmaceutically acceptable carrier” refers to a non-toxic, inert, solid, semi-solid substance or liquid filler, diluent, encapsulating material, or auxiliary formulation of any type of excipient that is compatible with the patient, preferably a mammal, more preferably a human, suitable for delivering the active agent to the target site without terminating the agent's activity. As used herein, “patient” refers to an animal, preferably a mammal, more preferably a human. The term “mammal” refers to warm-blooded vertebrate mammals, including such as cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, mice, pigs, and humans. As used herein, “treatment / treating” refers to alleviating, slowing progression, attenuating, preventing, or maintaining an existing disease or condition (e.g., cancer). Treatment / treating also includes curing, preventing the development of, or alleviating to some extent one or more symptoms of a disease or disorder. As used herein, the term “proteolysis targeting chimeras,” i.e., PROTAC, is a chemical molecule containing different ligands at both ends. One end is a ligand that binds to an E3 ligase (e.g., the ULM moiety of the present application), and the other end is a ligand that binds to an intracellular protein (e.g., the BTK-binding moiety of the present application). These two ligands are connected by a linker (e.g., L of the present application). Such a chemical molecule can bind to both an E3 ubiquitin ligase and an intracellular protein, bringing the targeted protein to the vicinity of the E3 ubiquitin ligase to achieve polyubiquitination of the target protein, which is then degraded by the proteasome. PROTACs can be recycled and are not degraded by the proteasome. As used herein, the term “capable of degrading BTK protein” means that the degradation ability against BTK protein is not less than 10% (degradation percentage >10%), and “capable of degrading IRAK4 protein” means that the degradation ability against IRAK4 protein is not less than 30% (degradation percentage >30%). The term “capable of simultaneously degrading BTK and IRAK4 proteins” means that the compound has a degradation ability of not less than 10%, or even not less than 30% or 50% or greater than 90%, against both target proteins. The term “treatment / treating” includes inhibiting, alleviating, preventing, or eliminating one or more symptoms or side effects associated with the disease, disorder, or condition being treated. As used herein, the term “ubiquitin ligase” refers to a family of proteins that promote the transfer of ubiquitin to specific substrate proteins, targeting the substrate proteins for degradation. For example, cereblon is an E3 ubiquitin ligase protein that, alone or in combination with an E2 ubiquitin-conjugating enzyme, causes the attachment of ubiquitin to lysine on the target protein, and subsequently targets specific protein substrates for degradation by the proteasome. Thus, an E3 ubiquitin ligase, alone or in complex with an E2 ubiquitin-conjugating enzyme, is responsible for the transfer of ubiquitin to the target protein. In general, ubiquitin ligases are involved in polyubiquitination, such that a second ubiquitin is attached to the first ubiquitin; a third ubiquitin is attached to the second ubiquitin, and so on. Polyubiquitination marks proteins for degradation by the proteasome. However, there are some ubiquitination events that are limited to monoubiquitination, where only a single ubiquitin is added to the substrate molecule by the ubiquitin ligase. Monoubiquitinated proteins are not targeted to the proteasome for degradation but may be altered in their cellular location or function, for example, by binding to other proteins that have domains capable of binding ubiquitin. More complexly, different lysines of ubiquitin can be targeted by E3 to produce chains. The most common lysine is Lys48 on the ubiquitin chain. This is the lysine used to make polyubiquitin recognized by the proteasome. II. EXAMPLES To clarify the objectives, technical solutions and advantages of the present application, the present application will be described in further detail below. The described examples shall not be construed as limitations on the present application. All other examples obtained by a person of ordinary skill in the art without creative efforts shall fall within the protection scope of the present application. Before further elaborating on the examples of the present application, the nouns and terms involved in the examples of the present application are defined, and the nouns and terms involved in the examples of the present application shall be interpreted as follows. The starting materials and equipment used in the specific embodiments of the present disclosure are all known products and can be obtained by purchasing commercially available products. Synthesis of Intermediate B1 HCl H2N B1 Step 1: Synthesis of methyl 4-(4-(dimethoxymethyl)piperidin-1-yl)-2-fluorobenzoate A mixture of 4-(dimethoxymethyl)piperidine (5.5 g, 34.9 mmol), methyl 2,4-difluorobenzoate (4 g, 23.3 mmol), and potassium carbonate (6.4 g, 46.6 mmol) in DMSO (40 mL) was purged with nitrogen three times, then heated to 80°C and stirred for 2 hours. The reaction mixture was cooled to room temperature, quenched with water, and extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (petroleum ether-ethyl acetate, from 95:5 to 90:10) to afford 3.5 g of the title compound as a white solid, yield 49%. MS (ESI) m / z = 312.0 [M+H]+. Step 2: Synthesis of 4-(4-(dimethoxymethyl)piperidin-1-yl)-2-fluorobenzoic acid A solution of lithium hydroxide monohydrate (7.9 g, 329.8 mmol) in water (60 mL) was slowly added to a solution of methyl 4-(4-(dimethoxymethyl)piperidin-1-yl)-2-fluorobenzoate (25.4 g, 82.5 mmol) in methanol (60 mL). The mixture was heated to 50°C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to remove methanol, diluted with water, and dilute hydrochloric acid was added dropwise with stirring until a large amount of precipitate formed. The mixture was filtered, and the filter cake was washed with water and dried to afford 20 g of the title compound as a white solid, yield 87.0%. MS (ESI) m / z = 298.1 [M+H]+. Step                            3:                            Synthesis                            of 4-(4-(dimethoxymethyl)piperidin-1-yl)-N-(2,6-dioxopiperidin-3-yl)-2-fluorobenzamide 2-(7-Azabenzotriazol-1-yl)-N,N,N‘,N‘-tetramethyluronium hexafluorophosphate (32.3 g, 85.5 mmol) was added in one portion to a solution of 4-(4-(dimethoxymethyl)piperidin-1-yl)-2-fluorobenzoic acid (17 g, 57 mmol), 3-aminopiperidine-2,6-dione hydrochloride (9.35 g, 57 mmol), and N,N-diisopropylethylamine (22.1 g, 171 mmol) in DMF (1700 mL). The mixture was stirred at room temperature for 1 hour. Water was added to quench the reaction, and the mixture was washed with ethyl acetate. The mixture was filtered to afford 17 g of the title compound as a pale yellow solid, yield 73.0%. MS (ESI) m / z = 408.3 [M+H]+. Step 4: Synthesis of N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(4-formylpiperidin-1-yl)benzamide Trifluoroacetic acid (17 mL) was added dropwise to a solution of 4-(4-(dimethoxymethyl)piperidin-1-yl)-N-(2,6-dioxopiperidin-3-yl)-2-fluorobenzamide (17 g, 41.7 mmol) in dichloromethane (170 mL). The mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, and the residue was adjusted to weakly basic pH with saturated sodium bicarbonate solution. DCM was added to extract the organic phase, which was concentrated to afford 12 g of the title compound as an off-white solid, yield 79%. MS (ESI) m / z = 362.1 [M+H]+. ‘H-NMR (400 MHz, DMSO-do) 5 10.85 (s, 1H), 9.62 (s, 1H), 8.03 (t, J = 7.2 Hz, 1H), 7.63 (t, J = 9.1 Hz, 1H), 6.97-6.64 (m, 2H), 4.76-4.72 (m, 1H), 3.82-3.76 (m, 2H), 3.06-3.02 (m, 2H), 2.79-2.73 (m, 1H), 2.502.52 (m, 2H), 2.19-1.97 (m, 2H), 1.93-1.86 (m, 2H), 1.57-1.51 (m, 2H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate B1: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ B2 ,0 0   .~.           _ °\ 374.2 B3 0 362.2 B4 0 378.1 B5 o=\ fsk.iNH ,--.    -- HN-<     Vn>_. O o N= /  \-- / 345.1 B6 < N-?  2—\   / --\ HN—)=O F        NH 0 334.1 B7 0 O=\ (SW'iiNH / ^=\ F 348.1 B8 F 380.1 B9 O= / (sY'iNH Y—X   Z\^F 352.1 B10 CsYnNH / =\   / --< OH HN-Z   —G Y— N Y^\ 0 0              ' xo F 378.1 B11 0 HN—¥ O= / Y—NH          / --< / p '  —\ / N o7 \= / x—' 344.2 B12 J? <V r^N-x j^u   NH O J                 H / / OCF3 0 428.1 B13 V>Qi£x>o \f3 y-NH 0 412.1 B14 0 w c> 374.2 B15 °=\ (sYhnh .—    __ HN1 oH>€Xo 344.2 B16 0 0 '-     0 \   ZI 0 348.1 B17 6 0 i^o I z if1 0 345.1 B18 ^"'NH Y—< hna O^>Y nvJho 0 \ 392.2 B19 0= / (S»«hNH N—a    / y hn—Z       y-N O oz )--   0 375.2 B20 H O O 345.1 B21 \ 374.2 B22 0 'Op ii 1 H o F 362.1 B23 0 0 345.1 B24 (____K 0 0     / ---\   [ / \ / ---\ J     N \     / ij»■   / i^\ --\ /   n=N            / x—1  N N     Vnh Q 346.1 B25 O JLl r z L s? Y^o O\^Z 317.1 B26 o r z L o 316.1 B27 o r z I _k ° O\^z 'l 1 . 316.1 B28 .   / --\   7=X    0 0 ° \X  N —<x z>—NH V   7       HN—y ^=O 370.2 B29 6 4 z J o 378.1 B30 s A z \\ o 346.1 Synthesis of Intermediate B31 B31 Step 1: Synthesis of tert-butyl 4-(3-fluoro-4-(methoxycarbonyl)phenyl)piperazine-1-carboxylate A mixture of tert-butyl piperazine-1-carboxylate (6.5 g, 34.9 mmol), methyl 2,4-difluorobenzoate (4 g, 23.3 mmol), and potassium carbonate (6.4 g, 46.6 mmol) in DMSO (40 mL) was purged with nitrogen three times, then heated to 80°C and stirred for 2 hours. The reaction mixture was cooled to room temperature, quenched with water, and extracted twice with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (petroleum ether-ethyl acetate, 95~90%) to afford 3.3 g of the title compound as a white solid, yield 41.5%. MS (ESI) m / z = 339.1 [M+H]+. Step 2: Synthesis of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-fluorobenzoic acid A solution of lithium hydroxide monohydrate (1.58 g, 37.6 mmol) in water (20 mL) was slowly added to a solution of tert-butyl 4-(3-fluoro-4-(methoxycarbonyl)phenyl)piperazine-1-carboxylate (3.3 g, 9.7 mmol) in methanol (20 mL). The mixture was heated to 50°C and stirred for 1 h. The reaction mixture was concentrated under reduced pressure to remove methanol, diluted with water, and dilute hydrochloric acid solution (1 mol / L) was added dropwise with stirring until a large amount of precipitate formed. The mixture was filtered, and the filter cake was washed with water and dried to afford 2.7 g of the title compound as a white solid, yield 85.9%. MS (ESI) m / z = 325.1 [M+H]+. Step                    3:                    Synthesis                    of                    tert-butyl (S)-4-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperazine-1-carboxylate 2-(7-Azabenzotriazol-1-yl)-N,N,N‘,N‘-tetramethyluronium hexafluorophosphate (4.7 g, 12.5 mmol) was added to a solution of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-2-fluorobenzoic acid (2.7 g, 8.3 mmol), (S)-3-aminopiperidine-2,6-dione hydrochloride (1.36 g, 8.3 mmol), and N,N-diisopropylethylamine (3.22 g, 24.9 mmol) in DMF (30 mL). The mixture was stirred at room temperature for 1 hour. Water was added to quench the reaction, and the mixture was washed with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (petroleum ether-ethyl acetate, 95~90%) to afford 3.0 g of the title compound as a white solid, yield 83.4%. MS (ESI) m / z = 435.2 [M+H]+. Step 4: Synthesis of (S)-N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(piperazin-1-yl)benzamide hydrochloride 4 M HCl in dioxane (6 mL) was added dropwise to a solution of tert-butyl (S)-4-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperazine-1-carboxylate (3.0 g, 6.9 mmol) in dichloromethane (30 mL). The mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure to afford 2.2 g of the title compound as an off-white solid, yield 95%. MS (ESI) m / z = 335.1 [M+H]+. The following intermediates were prepared according to the synthetic route and methods described for Intermediate B31: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ B32 0= /   / '"NH  z=\    / --v / HN—Z X—Z    N y—NH O O   / —'   '—' F 378.1 Synthesis of Intermediate B33 Step 1: Synthesis of 3-(6-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione Sodium acetate (5.4 g, 65.8 mmol) was added to a solution of 3-amino-2,6-piperidinedione hydrochloride (5.69 g, 36.2 mmol) in methanol (160 mL), followed by dropwise addition of glacial acetic acid (19.76 g, 0.33 mol). Methyl 5-bromo-2-formylbenzoate (8 g, 33 mmol) was added, followed by sodium cyanoborohydride (4.13 g, 65.8 mmol). The mixture was heated to 35°C and stirred for 16 hours. Water was added dropwise to the reaction mixture, then methanol was removed under reduced pressure. Water was added, and the mixture was filtered and dried to afford 8.3 g of the title compound as a white solid, yield 78.1%. MS (ESI) m / z = 323.0 / 325.0 [M+H]+. Step 2: Synthesis of 3-(6-(4-(dimethoxymethyl)piperidin-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (SP-4-1)-[1,3-Bis[2,6-bis(1-propylbutyl)phenyl]-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene]dichlor o(3-chloropyridine-KN)palladium   (0.3 g, 0.3 mmol) was added to a mixture of 3-(6-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione (2 g, 6.2 mmol), 4-(dimethoxymethyl)piperidine (1.28 g, 8.1 mmol), and cesium carbonate (6.06 g, 18.6 mmol) in dioxane (40 mL). The mixture was purged with nitrogen, then heated to 100°C and stirred for 3 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered. The filtrate was concentrated under reduced pressure and purified by column chromatography to afford 0.9 g of the title compound as a yellow solid, yield 35.5%. MS (ESI) m / z = 402.0 [M+H]+. Step 3: Synthesis of 1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidine-4-carbaldehyde trifluoroacetate Trifluoroacetic acid (6 mL) was added dropwise to a solution of 3-(6-(4-(dimethoxymethyl)piperidin-1-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (0.9 g, 2.2 mmol) in dichloromethane (20 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to afford 0.83 g of the title compound as a gray solid, yield 72.7%. MS (ESI) m / z = 356.2 [M+H]+. 'H-NMR (400 MHz, DMSO) 5 10.98 (s, 1H), 9.64 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.27 (m, 2H), 5.10 (dd, J = 13.3, 5.1 Hz, 1H), 4.34 (d, J = 16.7 Hz, 1H), 4.20 (d, J = 16.8 Hz, 1H), 3.67 (d, J = 12.6 Hz, 2H), 2.96-2.85 (m, 3H), 2.61-2.52 (m, 2H), 2.43-2.32 (m, 1H), 2.04-1.90 (m, 3H), 1.66-1.56 (m, 2H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate B33: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ B34 0 H if L N \ / 0 V NH 0 0 356.2 B35 0 |l J L N \ / 0 VnH 0 0 374.1 B36 0 H F T L n \ / ° NH 0 0 374.1 B37 2            Q HN^<yv<y 0    ' F 374.1 B38 X ^=° 2^ \    / — 2  ° 2 J o 374.1 B39 s o r 2=o ^2 2^ / 1 u o 342.1 B40 / =° -n   2—' 2 J o 374.1 B41 / =° 2—' ■n—K 2  ° 2 J o 374.1 Synthesis of Intermediate B42 Step                            1:                            Synthesis                            of 2-(2,6-dioxopiperidin-3-yl)-5-(4-(hydroxymethyl)piperidin-1-yl)isoindoline-1,3-dione N,N-Diisopropylethylamine   (4.21 g, 32.58 mmol) was added to a solution of 2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione (1.80 g, 6.52 mmol) and piperidin-4-ylmethanol (0.83 g, 7.17 mmol) in DMSO (15 mL). The mixture was heated to 120°C and stirred for 2 hours. After completion, the mixture was concentrated under reduced pressure, and the residue was purified by C18 column chromatography to afford 2.2 g of the title compound as a yellow solid, yield 90%. MS (ESI) m / z = 372.1 [M+H]+. Step 2: Synthesis of 1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidine-4-carbaldehyde At                                     room                                     temperature, 2-(2,6-dioxopiperidin-3-yl)-5-(4-(hydroxymethyl)piperidin-1-yl)isoindoline-1,3-dione (2.00 g, 5.39 mmol) was dissolved in dichloromethane (50 mL). Pyridinium chlorochromate (5.80 g, 26.93 mmol) was added in portions to the reaction mixture, which was then stirred at room temperature for 2 hours. The reaction mixture was filtered, and the filtrate was concentrated to give the crude product, which was purified to afford 668 mg of the title compound as a yellow solid, yield 32.4%. MS (ESI) m / z = 370.0 [M+H]+. 'H-NMR (400 MHz, DMSO) 5 11.09 (s, 1H), 9.62 (s, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.34 (d, J = 2.1 Hz, 1H), 7.25 (dd, J = 8.6, 2.2 Hz, 1H), 5.07 (dd, J = 12.9, 5.4 Hz, 1H), 3.94 (d, J = 13.4 Hz, 2H), 3.23-3.11 (m, 2H), 2.92-2.85 (m, 1H), 2.70-2.51 (m, 3H), 2.05-1.86 (m, 3H), 1.59-1.50 (m, 2H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate B42: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ B43 O /  ZI °VZ ° T y=o z or 410.2 B44 0^0 L z n1 o 356.1 B45 O 0 Vnh '0 342.1 B46 396.1 Synthesis of Intermediate B47 B47 Step                    1:                    Synthesis                    of                   tert-butyl 4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)piperazine-1-carboxylate N,N-Diisopropylethylamine   (2.34 g, 18.10 mmol) was added to a solution of 2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindoline-1,3-dione   (1.00 g, 3.62 mmol) and   tert-butyl 4-(azetidin-3-yl)piperazine-1-carboxylate (2.09 g, 8.69 mmol) in DMSO (10 mL). The mixture was heated to 120°C and stirred for 2 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography to afford 1.2 g of the title compound as a yellow solid, yield 69.8%. MS (ESI) m / z = 498.2 [M+H]+. Step 2: Synthesis of 2-(2,6-dioxopiperidin-3-yl)-5-(3-(piperazin-1-yl)azetidin-1-yl)isoindoline-1,3-dione hydrochloride 4 M HCl in dioxane (4 mL) was added dropwise to a solution of tert-butyl 4-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)piperazine-1-carboxylate (1.2 g, 2.4 mmol) in dichloromethane (20 mL). The mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated to afford 2.2 g of the title compound as a yellow solid. MS (ESI) m / z = 398.1 [M+H]+. The following intermediates were prepared according to the synthetic route and methods described for Intermediate B47: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ B48 O \\ i z'2 V / ^o z^° o= / J ^2 z^y i 397.2 B49 °Vzo-y" 371.2 Synthesis of Intermediate B50 0H                                                                                                         B50 Step 1: Synthesis of (1-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperidin-4-yl)methyl acetate Glacial acetic acid (4.70 g, 78.2 mmol) was added to a solution of (1-(4-aminophenyl)piperidin-4-yl)methanol (6.8 g, 33.0 mmol) and acrylic acid (2.38 g, 33 mmol) in water (8 mL). The mixture was purged with nitrogen three times, then heated to 105°C and stirred for 20 h. After cooling to room temperature, a solution of urea (9.91 g, 0.165 mol) in glacial acetic acid (70 mL) was added. The mixture was purged with nitrogen, then heated to 120°C and stirred for 20 h. After completion, hydrochloric acid (14 mL) was added, and the mixture was heated to 120°C and stirred for 1 h. After cooling to room temperature, water was added to dilute, the pH was adjusted to 8, and the mixture was extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 5 g of the title compound as a pink solid, yield 23%. MS (ESI) m / z = 346.3 [M+H]+. Step 2: Synthesis of 1-(4-(4-(hydroxymethyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione A solution of (1-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperidin-4-yl)methyl acetate (5 g, 0.0072 mol) in hydrochloric acid (50 mL, 2 mol / L) was purged with nitrogen, then heated to 100°C and stirred for 16 h. After cooling to room temperature, water was added to dilute, pH was adjusted to 8, and the mixture was extracted with ethyl acetate. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 3 g of the title compound as a pink solid, yield 68%. MS (ESI) m / z = 304.3 [M+H]+. Step 3: Synthesis of 1-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)phenyl)piperidine-4-carbaldehyde trifluoroacetate Dess-Martin periodinane (5.09 g, 12 mmol) was added to a solution of 1-(4-(4-(hydroxymethyl)piperidin-1-yl)phenyl)dihydropyrimidine-2,4(1H,3H)-dione (1.2 g, 0.004 mol) in DMF (30 mL). The mixture was purged with nitrogen three times, then stirred at 25°C for 2 hours. After completion, water was added to dilute, the mixture was filtered, and the filtrate was concentrated. The residue was purified by column chromatography to afford 347 mg of the title compound as a brown solid, yield 31.4%. MS (ESI) m / z = 302.1 [M+H]+. 'H-NMR (400 MHz, DMSO) 5 10.33 (s, 1H), 9.64 (s, 1H), 7.21 (t, J = 22.7 Hz, 4H), 3.72 (t, J = 6.7 Hz, 2H), 3.67-3.55 (m, 2H), 3.03 (s, 2H), 2.68 (t, J = 6.7 Hz, 2H), 2.57 (t, J = 10.6 Hz, 1H), 2.04-1.96 (m, 2H), 1.72-1.62 (m, 2H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate B50: B53 / 0 o=^ n—r / \—K HN~^ / = / ' x0 O F 350.1 B54 o ft 9 350.1 B55 HN-Z \=N   '--'  0 0 303.1 B56 0 HN^ / r~\ / \ / ° o=^ 7N / N0— 274.1 B57 0 HN^ / =x   / - N—(( Vn \ \—z        — / 0 302.1 Synthesis of Intermediate B58 H B58 Step 1: Synthesis of 3-((4-bromo-2,6-difluorophenyl)amino)propanoic acid Tetrabutylammonium bromide (0.700 g, 2.18 mmol) was added in portions to a solution of 4-bromo-2,6-difluoroaniline (4.51 g, 21.8 mmol) and acrylic acid (1.73 g, 23.9 mmol) in dilute hydrochloric acid (48 mL, 2 mol / L). The mixture was heated to 100°C and stirred for 16 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, and purified by column chromatography to afford 3.25 g of the title compound as a yellow solid, yield 53.5%. MS (ESI) m / z = 280.0 / 282.0 [M+H]+. Step 2: Synthesis of 1-(4-bromo-2,6-difluorophenyl)dihydropyrimidine-2,4(1H,3H)-dione Sodium cyanate (3.67 g, 0.0565 mol) was added to a solution of 3-((4-bromo-2,6-difluorophenyl)amino)propanoic acid (3.3 g, 0.0113 mol) in acetic acid (33 mL). The mixture was heated to 120°C and stirred for 16 hours. The reaction mixture was concentrated under reduced pressure, ice water was added to precipitate the product, which was filtered and dried to afford 1.98 g of the title compound as a gray solid, yield 62.8%. MS (ESI) m / z = 305.0 / 307.0 [M+H]+. Step                    3:                    Synthesis                    of                    tert-butyl 1-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-3,5-difluorophenyl)piperidine-4-carboxylate Methanesulfonato(2-dicyclohexylphosphino-2‘,6‘-diisopropoxy-1,1‘-biphenyl)(2‘-amino-1,1‘-biphenyl-2-y l)palladium(II) (544.18 mg, 0.650 mmol) was added to a mixture of 1-(4-bromo-2,6-difluorophenyl)dihydropyrimidine-2,4(1H,3H)-dione (1.32 g, 4.33 mmol), tert-butyl piperidine-4-carboxylate (801 mg, 4.33 mmol), 2-dicyclohexylphosphino-2‘,6‘-diisopropoxy-1,1‘-biphenyl (303 mg, 0.650 mmol), and sodium tert-butoxide (4.23 g, 13.0 mmol) in dioxane (50 mL). The mixture was purged with nitrogen, then heated to 100°C and stirred for 1 hour. The reaction mixture was concentrated under reduced pressure and purified by column chromatography to afford 377.4 mg of the title compound as a yellow solid, yield 21.3%. MS (ESI) m / z = 410.2 [M+H]+. Step                            4:                            Synthesis                            of 1-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-3,5-difluorophenyl)piperidine-4-carboxylic acid Trifluoroacetic acid (3     mL) was added to a solution of    tert-butyl 1-(4-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-3,5-difluorophenyl)piperidine-4-carboxylate (377.4 mg, 0.92 mmol) in dichloromethane (9 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by column chromatography to afford 211.8 mg of the title compound as a blue solid, yield 65.2%. MS (ESI) m / z = 354.1 [M+H]+. The following intermediates were prepared according to the synthetic route and methods described for Intermediate B58: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ B59 0^N_^yNQH° hn-< )= /       oh 0 F 336.1 Synthesis of Intermediate B60 Step                    1:                    Synthesis                    of                   tert-butyl 1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-3,5-difluorophenyl)piperidine-4-carboxylate Bis(dibenzylideneacetone)palladium (570 mg, 0.622 mmol) was added to a mixture of 2-dicyclohexylphosphino-2‘,4‘,6‘-triisopropylbiphenyl         (593         mg,         1.24         mmol), 2,6-bis(benzyloxy)-3-(4-bromo-2,6-difluorophenyl)pyridine    (3.00 g, 6.22 mmol),    tert-butyl piperidine-4-carboxylate (1.73 g, 9.33 mmol), and sodium tert-butoxide (1.20 g, 12.4 mmol) in dioxane (30 mL). The mixture was purged with nitrogen, then heated to 100°C and stirred for 1 hour. The reaction mixture was concentrated under reduced pressure and purified by column chromatography to afford 1.30 g of the title compound as a pale yellow oil, yield 35.6%. MS (ESI) m / z = 587.1 [M+H]+. Step 2: Synthesis of tert-butyl 1-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)piperidine-4-carboxylate Palladium on carbon (0.65 g, 50% wt) was added to  a solution of tert-butyl 1-(4-(2,6-bis(benzyloxy)pyridin-3-yl)-3,5-difluorophenyl)piperidine-4-carboxylate (1.30 g, 2.22 mmol) in ethyl acetate (50 mL). The mixture was purged with hydrogen and stirred at room temperature. After completion, the reaction mixture was filtered through Celite, and the filtrate was concentrated to afford 700 mg of the title compound as a blue solid, yield 77.3%. MS (ESI) m / z = 408.9 [M+H]+. Step 3: Synthesis of 1-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)piperidine-4-carboxylic acid Trifluoroacetic acid (2 mL) was added to a solution of    tert-butyl 1-(4-(2,6-dioxopiperidin-3-yl)-3,5-difluorophenyl)piperidine-4-carboxylate (700 mg, 3.80 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by column chromatography to afford 532 mg of the title compound as a blue-gray solid, yield 66.6%. MS (ESI) m / z = 353.0 [M+H]+. 'H-NMR (400 MHz, DMSO-de) 5 12.23 (s, 1H), 10.87 (s, 1H), 6.63 (d, J = 12.8 Hz, 2H), 4.04 (dd, J = 12.2, 4.6 Hz, 1H), 3.69 (d, J = 12.6 Hz, 2H), 2.93-2.70 (m, 3H), 2.48-2.38 (m, 1H), 2.18-2.03 (m, 1H), 2.01-1.91 (m, 1H), 1.90-1.79 (m, 2H), 1.65-1.49 (m, 2H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate B60: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ B61 0 HN \         / —\ 0H °=< }— / V- n 2—Z 317.1 B62 —0 / —v         / —k 0 O=\   / —X / N / —\ HN—Z )= /  '--' OH O F 365.1 B63 O F HN—¥  2=\   / --v OH °=^ 2—K    n 2— \-- /  \__7   \-- / xo 335.1 B64 0 F\ HN^ \=N / <   O o=( / —4 zHN / — \ '            X' OH 336.1 B65 0 HN^ / =   / -\ OH o=^ / —4       / — '---'               X' O O 348.1 B66 0 F\ HN^ >=   / -\ OH o=( / —4 # N )— \--- / \--- / 'o —O 365.1 B67 —0 / —\       / —\ p °=\  )—C y—N  )— HN~^        X' OH O 347.2 Synthesis of Intermediate B68 Step 1: Synthesis of 2,6-bis(benzyloxy)-3-(4-bromo-2-fluoro-6-methoxyphenyl)pyridine Tetrakis(triphenylphosphine)palladium (0.89 g, 0.77 mmol) was added to a solution of 5-bromo-1-fluoro-2-iodo-3-methoxybenzene           (2.54           g,            7.7           mmol), 2,6-bis(benzyloxy)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (4.84 g, 11.6 mmol), and sodium carbonate (2.45 g, 23.1 mmol) in dioxane (40 mL). Water (10 mL) was added, the mixture was purged with nitrogen, then heated to 90°C and stirred for 16 hours. After completion, water was added to dilute, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 2.0 g of the title compound as a white solid, yield 85.7%. MS (ESI) m / z = 494.1 [M+H]+. Step                            2:                            Synthesis                            of 2,6-bis(benzyloxy)-3-(4-(4-(dimethoxymethyl)piperidin-1-yl)-2-fluoro-6-methoxyphenyl)pyridine Tris(dibenzylideneacetone)dipalladium          (354.36          mg,          0.39          mmol), 2-dicyclohexylphosphino-2‘,6‘-dimethoxybiphenyl (238.29 mg, 0.58 mmol), and cesium carbonate (3.78 g, 11.6       mmol)       were       sequentially       added       to       a       solution       of 2,6-bis(benzyloxy)-3-(4-bromo-2-fluoro-6-methoxyphenyl)pyridine    (1.9 g, 3.87 mmol) and 4-(dimethoxymethyl)piperidine (615.7 mg, 3.87 mmol) in DMF (50 mL). The mixture was purged with nitrogen, then heated to 110°C and stirred for 10 h. The mixture was cooled to room temperature, water was added to dilute, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 956.7 mg of the title compound as a yellow oil, yield 43.2%. MS (ESI) m / z = 573.3 [M+H]+. Step                            3:                            Synthesis                            of 3-(4-(4-(dimethoxymethyl)piperidin-1-yl)-2-fluoro-6-methoxyphenyl)piperidine-2,6-dione 10% Palladium on carbon (96 mg) was added to a solution of 2,6-bis(benzyloxy)-3-(4-(4-(dimethoxymethyl)piperidin-1-yl)-2-fluoro-6-methoxyphenyl)pyridine (956.7 mg, 1.67 mmol) in ethyl acetate (50 mL). The mixture was purged with hydrogen and stirred at room temperature. After completion, the reaction mixture was filtered through Celite, and the filtrate was concentrated to afford 497.0 mg of the title compound as a blue solid, yield 75.5%. MS (ESI) m / z = 395.2 [M+H]+. Step 4: Synthesis of 1-(4-(2,6-dioxopiperidin-3-yl)-3-fluoro-5-methoxyphenyl)piperidine-4-carbaldehyde Trifluoroacetic acid (2 mL) was added dropwise to a solution of 3-(4-(4-(dimethoxymethyl)piperidin-1-yl)-2-fluoro-6-methoxyphenyl)piperidine-2,6-dione (497 mg, 1.26 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by column chromatography to afford 170 mg of the title compound as an off-white solid, yield 38.9%. MS (ESI) m / z = 349.1 [M+H]+. Synthesis of Intermediate B69 OH Step                            1:                            Synthesis                            of 3-[4-(3-{[4-(hydroxymethyl)cyclohexyl]oxy}prop-1-yn-1-yl)-3-methyl-2-oxo-1,3-benzodiazol-1-yl]piperidine -2,6-dione Bis(acetonitrile)dichloropalladium (13.04 mg, 0.06 mmol) was added to a solution of [4-(prop-2-yn-1-yloxy)cyclohexyl]methanol          (1691.51          mg,          10.0          mmol), 3-(4-bromo-3-methyl-2-oxo-1,3-benzodiazol-1-yl)piperidine-2,6-dione (1700 mg, 5.02 mmol), cesium carbonate (4.91 g, 15.08 mmol), copper(I) iodide (9.57 mg, 0.06 mmol), and 2-dicyclohexylphosphino-2‘,4‘,6‘-triisopropylbiphenyl (47.93 mg, 0.1 mmol) in DMF (60 mL). The mixture was heated to 80°C under nitrogen protection and stirred for 1 hour. After cooling, the reaction mixture was filtered, and the filtrate was concentrated and purified by column chromatography to afford 720 mg of the title compound as a white solid, yield 34.0%. MS (ESI) m / z = 426.1 [M+H]+. Step                            2:                            Synthesis                            of 4-({3-[1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-1,3-benzodiazol-4-yl]prop-2-yn-1-yl}oxy)cyclohexane-1-c arbaldehyde Dess-Martin periodinane (837.35 mg, 1.97 mmol) was added in portions to a solution of 3-[4-(3-{[4-(hydroxymethyl)cyclohexyl]oxy}prop-1-yn-1-yl)-3-methyl-2-oxo-1,3-benzodiazol-1-yl]piperidine -2,6-dione (700 mg, 1.65 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by column chromatography to afford 261.0 mg of the title compound as a white solid, yield 37.4%. MS (ESI) m / z = 424.2 [M+H]+. 'H-NMR (400 MHz, DMSO) 5 11.09 (s, 1H), 9.53 (s, 1H), 7.13 (d, J = 7.8 Hz, 1H), 7.08 (d, J = 6.8 Hz, 1H), 6.99 (t, J = 7.9 Hz, 1H), 5.435.26 (m, 1H), 4.49-4.31 (m, 2H), 3.60 (s, 3H), 3.52-3.37 (m, 1H), 2.94-2.78 (m, 1H), 2.76-2.52 (m, 2H), 2.22 (s, 1H), 2.09-1.94 (m, 3H), 1.90 (d, J = 12.3 Hz, 1H), 1.73-1.48 (m, 1H), 1.40-1.01 (m, 4H). The following intermediates were prepared according to the synthetic route and methods described for B71 Step                            1:                            Synthesis                            of 1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-4-carbaldehyde 3-(4-Bromo-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-2,6-dione (1.40 g, 4.14 mmol) was dissolved in DMF (60 mL), then triethylamine (1.26 g, 12.42 mmol), triethylsilane (1.44 g, 12.42 mmol), and Pd(dppf)Ch (1.20 g, 1.66 mmol) were sequentially added. The reaction was heated to 120°C under a carbon monoxide atmosphere and stirred for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated. The residue was purified by column chromatography to afford 870 mg of the title compound as a pale yellow solid. MS (ESI) m / z = 288.1 [M+H]+. Step                    2:                    Synthesis                    of                    tert-butyl (1-((1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)methyl)piperidin-4-yl )(methyl)carbamate Titanium(IV) isopropoxide (1205 mg, 4.24 mmol) was added to a solution of 1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-4-carbaldehyde (870 mg, 2.12 mmol) and tert-butyl methyl(piperidin-4-yl)carbamate (1363 mg, 6.36 mmol) in DMF (70 mL) and THF (70 mL). The reaction was heated to 50°C and stirred for 16 hours. Sodium triacetoxyborohydride (1348 mg, 6.36 mmol) was then added to the reaction mixture and stirred at room temperature for 0.5 h. The reaction mixture was concentrated, and the residue was purified by column chromatography to afford 600 mg of the title compound as a pale yellow solid, yield 40.8%. MS (ESI) m / z = 486.1 [M+H]+. Step                            3:                            Synthesis                            of 3-(3-methyl-4-((4-(methylamino)piperidin-1-yl)methyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidi ne-2,6-dione trifluoroacetate At room temperature, tert-butyl (1-((1-(2,6-dioxopiperidin-3-yl)-3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)methyl)piperidin-4-yl )(methyl)carbamate (600 mg, 0.87 mmol) was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (2 mL), and stirred at room temperature for 1 hour. The reaction mixture was concentrated, and the crude product was purified by column chromatography to afford 310 mg of the title compound as a yellow solid, yield 58.4%. MS (ESI) m / z = 386.1 [M+H]+. Synthesis of Intermediate B72 HO HO Step 1: Synthesis of                     tert-butyl 2-(1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-methyl-1H-indazol-6-yl)-4-hydroxypiperidin-4-yl)acetate Methanesulfonato(2-dicyclohexylphosphino-2‘,6‘-diisopropoxy-1,1‘-biphenyl)(2‘-amino-1,1‘-biphenyl-2-y l)palladium(II)    (544.2    mg,    0.65    mmol)    was    added    to    a    mixture    of 1-(6-bromo-1-methyl-1H-indazol-3-yl)dihydropyrimidine-2,4(1H,3H)-dione (1.4 g, 4.33 mmol), tert-butyl 2-(4-hydroxypiperidin-4-yl)acetate             (932.7             mg,             4.33             mmol), 2-dicyclohexylphosphino-2‘,6‘-diisopropoxy-1,1‘-biphenyl (303.2 mg, 0.65 mmol), and cesium carbonate (4.23 g, 13.0 mmol) in dioxane (50 mL). The mixture was purged with nitrogen, then heated to 100°C and stirred for 16 hours. The reaction mixture was concentrated and purified by column chromatography to afford 550 mg of the title compound as a yellow solid, yield 27.7%. MS (ESI) m / z = 458.0 [M+H]+. Step                            2:                            Synthesis                            of 2-(1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-methyl-1H-indazol-6-yl)-4-hydroxypiperidin-4-yl)acetic acid Trifluoroacetic acid (3 mL) was added dropwise to a solution of tert-butyl 2-(1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-methyl-1H-indazol-6-yl)-4-hydroxypiperidin-4-yl)acetate (550 mg, 1.2 mmol) in dichloromethane (3 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by C18 column chromatography to afford 441 mg of the title compound as a white solid, yield 90.2%. MS (ESI) m / z = 402.2 [M+H]+. ‘H-NMR (400 MHz, DMSO) 5 10.53 (s, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7.14-7.01 (m, 2H), 3.95-3.82 (m, 5H), 3.58-3.47 (m, 2H), 3.31 (s, 2H), 2.74 (t, J = 6.7 Hz, 2H), 2.43 (s, 2H), 1.95-1.84 (m, 2H), 1.79-1.71 (m, 2H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate B72: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ B73 HO / --, F ho / irv0 o     V A / NvNH N-N o / 420.2 Synthesis of Intermediate B74 B74 Step                              1:                              Synthesis of 1-(6-(4-(dimethoxymethyl)piperidin-1-yl)-1-methyl-1H-indazol-3-yl)dihydropyrimidine-2,4(1H,3H)-dione Cesium            carbonate             (7.53             g,            23.1             mmol), methanesulfonato(2-dicyclohexylphosphino-2‘,6‘-diisopropoxy-1,1‘-biphenyl)(2‘-amino-1,1‘-biphenyl-2-yl)pall adium(II) (0.97 g, 1.1 mmol), and 2-dicyclohexylphosphino-2‘,6‘-diisopropoxy-1,1‘-biphenyl (0.54 g, 1.1 mmol)           were           added           to           a           solution           of 1-(6-bromo-1-methyl-1H-indazol-3-yl)dihydropyrimidine-2,4(1H,3H)-dione (2.5 g, 7.7 mmol) and 4-(dimethoxymethyl)piperidine (1.23 g, 7.7 mmol) in 1,4-dioxane (30 mL). The mixture was purged with nitrogen, then heated to 100°C and stirred for 16 hours. After cooling to room temperature, water was added to dilute, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 1.1 g of the title compound as a yellow oil, yield 20.8%. MS (ESI) m / z = 402.0 [M+H]+. Step                            2:                            Synthesis                            of 1-(3-(2,4-dioxotetrahydropyrimidin-1(2H)-yl)-1-methyl-1H-indazol-6-yl)piperidine-4-carbaldehyde trifluoroacetate Trifluoroacetic      acid      (2      mL)      was      added      to      a      solution      of 1-(6-(4-(dimethoxymethyl)piperidin-1-yl)-1-methyl-1H-indazol-3-yl)dihydropyrimidine-2,4(1H,3H)-dione (1 g, 2.5 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated at low temperature and purified by column chromatography to afford 534.8 mg of the title compound as a white solid, yield 58.2%. MS (ESI) m / z = 356.1 [M+H]+. 'H-NMR (400 MHz, DMSO) 5 10.51 (s, 1H), 9.66 (s, 1H), 7.47 (d, J = 8.7 Hz, 1H), 6.94 (d, J = 8.1 Hz, 2H), 3.91-3.87 (m, 5H), 3.70 (dd, J = 8.9, 3.8 Hz, 2H), 2.97 (s, 2H), 2.73 (t, J = 6.7 Hz, 2H), 2.58-2.55 (m, 1H), 2.04-1.97 (m, 2H), 1.72-1.62 (m, 2H). Synthesis of Intermediate B75 Step                            1:                            Synthesis                            of 3-[2,6-bis(benzyloxy)pyridin-3-yl]-6-[4-(dimethoxymethyl)piperidin-1-yl]-1-methylindazole Palladium(II) acetate (197.4 mg, 0.799 mmol) was added to a solution of 3-[2,6-bis(benzyloxy)pyridin-3-yl]-6-bromo-1-methylindazole       (2.0       g,       3.99       mmol), 4-(dimethoxymethyl)piperidine (636.4 mg, 3.99 mmol), cesium carbonate (3.90 g, 11.99 mmol), and 1,r—bmaphthyl—2,2‘—diylbis(diphenylphosphme) (497.7 mg, 0.799 mmol) in toluene (20 mL). The mixture was heated to 100°C and stirred for 15 hours under nitrogen protection. The mixture was extracted with ethyl acetate, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 1.3 g of the title compound as a yellow solid, yield 56.2%. MS (ESI) m / z = 579.2 [M+H]+. Step                            2:                            Synthesis                            of 3-{6-[4-(dimethoxymethyl)piperidin-1-yl]-1-methylindazol-3-yl}piperidine-2,6-dione Palladium on carbon (441.3 mg, 0.415 mmol, 10%) was added to a solution of 3-[2,6-bis(benzyloxy)pyridin-3-yl]-6-[4-(dimethoxymethyl)piperidin-1-yl]-1-methylindazole (1.2 g, 2.07 mmol) in ethyl acetate. The mixture was purged with hydrogen and stirred at room temperature for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated and purified by column chromatography to afford 600 mg of the title compound as a yellow solid, yield 61.4%. MS (ESI) m / z = 401.2 [M+H]+. Step 3: Synthesis of 1-[3-(2,6-dioxopiperidin-3-yl)-1-methylindazol-6-yl]piperidine-4-carbaldehyde Trifluoroacetic acid (5 mL) was added dropwise to a solution of 3-{6-[4-(dimethoxymethyl)piperidin-1-yl]-1-methylindazol-3-yl}piperidine-2,6-dione (550 mg, 1.37 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated and purified by column chromatography to afford 432.5 mg of the title compound as a white solid, yield 87.8%. MS (ESI) m / z = 355.2 [M+H]+. 'H-NMR (400 MHz, DMSO) 5 10.89 (s, 1H), 9.66 (s, 1H), 7.58 (d, J = 8.9 Hz, 1H), 7.11 (s, 1H), 7.02 (d, J = 8.8 Hz, 1H), 4.29 (dd, J = 9.5, 5.0 Hz, 1H), 3.92 (s, 3H), 3.70 (d, J = 12.5 Hz, 2H), 3.07 (t, J = 11.2 Hz, 2H), 2.72-2.54 (m, 3H), 2.39-2.25 (m, 1H), 2.22-2.10 (m, 1H), 2.07-1.98 (m, 2H), 1.79-1.63 (m, 2H). Synthesis of Intermediate B76 Step 1: Synthesis of 7-(4-nitro-2-(trifluoromethyl)phenyl)-7-azaspiro[3.5]nonan-2-one N,N-Diisopropylethylamine (6.63 g, 51.3 mmol) was added to a solution of 7-azaspiro[3.5]nonan-2-one hydrochloride (3.0 g, 17.1 mmol) and 1-fluoro-4-nitro-2-(trifluoromethyl)benzene (3.59 g, 17.1 mmol) in DMSO (30 mL). The mixture was purged with nitrogen, then heated to 120°C and stirred for 16 hours. After completion, the mixture was cooled to room temperature, water was added to dilute, the mixture was extracted with dichloromethane, the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 3.2 g of the title compound as a brown solid, yield 56.7%. MS (ESI) m / z = 329.1 [M+H]+. Step 2: Synthesis of 7-(4-amino-2-(trifluoromethyl)phenyl)-7-azaspiro[3.5]nonan-2-one Palladium on carbon (0.32 g, 10% wt) was added to a solution of 7-(4-nitro-2-(trifluoromethyl)phenyl)-7-azaspiro[3.5]nonan-2-one (3.2 g, 9.7 mmol) in methanol (50 mL). The mixture was purged with hydrogen, then stirred at 25°C for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated to afford 2.2 g of the title compound as a brown solid, yield 49.5%. MS (ESI) m / z = 299.1 [M+H]+. Step                            3:                            Synthesis                            of 7-(4-((2,6-bis(benzyloxy)pyridin-3-yl)amino)-2-(trifluoromethyl)phenyl)-7-azaspiro[3.5]nonan-2-one Tris(dibenzylideneacetone)dipalladium (0.68 g, 0.74 mmol) was added to a mixture of 7-(4-amino-2-(trifluoromethyl)phenyl)-7-azaspiro[3.5]nonan-2-one      (2.2      g,      7.4      mmol), 2,6-bis(benzyloxy)-3-bromopyridine              (3.29             g,              8.9             mmol), 2-dicyclohexylphosphino-2‘,6‘-diisopropoxy-1,1‘-biphenyl (0.35 g, 0.74 mmol), and cesium carbonate (7.23 g, 22.2 mmol) in tert-butanol (100 mL). The mixture was purged with nitrogen, then heated to 100°C and stirred for 16 hours. The reaction mixture was cooled to room temperature, water was added, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 1.2 g of the title compound as a white solid, yield 25.7%. MS (ESI) m / z = 588.2 [M+H]+. Step                            4:                            Synthesis                            of 3-((4-(2-oxo-7-azaspiro[3.5]nonan-7-yl)-3-(trifluoromethyl)phenyl)amino)piperidine-2,6-dione Palladium on carbon (0.36 g, 30% wt) was added to a solution of 7-(4-((2,6-bis(benzyloxy)pyridin-3-yl)amino)-2-(trifluoromethyl)phenyl)-7-azaspiro[3.5]nonan-2-one (1.2 g, 2.0 mmol) in ethyl acetate (100 mL). The mixture was purged with hydrogen and stirred at room temperature overnight. The reaction mixture was filtered, and the filtrate was concentrated to afford 0.3 g of the title compound as a white solid, yield 35.0%. MS (ESI) m / z = 410.1 [M+H]+. 'H-NMR (400 MHz, DMSO) 5 10.79 (s, 1H), 7.28 (d, J = 8.7 Hz, 1H), 6.94-6.85 (m, 2H), 4.71 (brs, 1H), 4.38 (dd, J = 11.5, 4.8 Hz, 1H), 2.92-2.71 (m, 4H), 2.78-2.66 (m, 5H), 2.63-2.53 (m, 1H), 2.12-2.03 (m, 1H), 1.95-1.86 (m, 1H), 1.79-1.68 (m, 4H). The following intermediates were prepared according to the synthetic route and methods described for B78 Step 1: Synthesis of tert-butyl 4-(3-amino-4-cyano-1H-pyrazol-1-yl)piperidine-1-carboxylate 3-Amino-1H-pyrazole-4-carbonitrile (4.0 g, 37 mmol), 4-((methylsulfonyl)oxy)piperidine-1-carboxylate (15.52 g, 55.5 mmol), and cesium carbonate (24.1 g, 74 mmol) were dissolved in DMF (100 mL) and stirred at 80°C overnight. Water was added to quench, and the mixture was extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford the title compound (5.2 g, yellow solid, yield 48.2%). MS (ESI) m / z: 236.1 [M-56+H]+. Step 2: Synthesis of tert-butyl 4-(3-amino-4-carbamoyl-1H-pyrazol-1-yl)piperidine-1-carboxylate In an ice-water bath, 30% hydrogen peroxide (3.5 mL, 34.4 mmol) was added dropwise to a solution of 4-(3-amino-4-cyano-1H-pyrazol-1-yl)piperidine-1-carboxylate (5.0 g, 17.2 mmol), potassium carbonate (470 mg, 3.44 mmol), and DMSO (50 mL). The mixture was stirred at room temperature for 4 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with water, dried over Na2SO4, filtered, and concentrated. The residue was triturated with (PE / EA, 10 / 1), filtered to afford the title compound (2.63 g, white solid, yield 48.6%). MS (ESI) m / z: 332.1 [M+Na]+. HNMR (400 MHz, DMSO-de) 5: 7.96 (s, 1H), 7.17 (s, 1H), 6.72 (s, 1H), 5.37 (s, 2H), 3.90-4.12 (m, 3H), 2.88 (s, 2H), 1.90-2.00 (m, 2H), 1.54-1.68 (m, 2H), 1.41 (s, 9H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate C1: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ C2 WNH2 BocnQ>—N^L. NH2 0 282.1 Synthesis of Intermediate C3 Step 1: 5-Nitro-4-(piperidin-1-yl)pyridin-2-amine 4-Chloro-5-nitropyridin-2-amine (20.0 g, 115.2 mmol), N,N-diisopropylethylamine (29.5 g, 345.6 mmol), and piperidine (29.5 g, 345.6 mmol) were dissolved in THF (250 mL) and stirred at 70°C overnight. Water was added to quench, the mixture was extracted with ethyl acetate, the organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford 20.5 g of a yellow solid, yield 80.1%). MS (ESI) m / z: 223.1 [M+H]+. Step 2: tert-Butyl 4-(6-nitro-7-(piperidin-1-yl)imidazo[1,2-a]pyridin-2-yl)piperidine-1-carboxylate 5-Nitro-4-(piperidin-1-yl)pyridin-2-amine (6.0 g, 27.00 mmol) was dissolved in ethanol (100 mL), then 4-(2-bromoacetyl)piperidine-1-carboxylate (5.82 g, 29.7 mmol) was added. The reaction mixture was stirred at 120°C for 40 hours. The reaction mixture was poured into water and extracted with dichloromethane. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford the title compound 3.5 g as a red solid, yield 30.2%. MS (ESI) m / z: 430.2 [M+H]+. Step                    3:                    Synthesis                    of                    tert-butyl 4-(6-amino-7-(piperidin-1-yl)imidazo[1,2-a]pyridin-2-yl)piperidine-1-carboxylate tert-Butyl 4-(6-nitro-7-(piperidin-1-yl)imidazo[1,2-a]pyridin-2-yl)piperidine-1-carboxylate (3.5 g, 8.14 mmol) was dissolved in methanol (100 mL), then Pd / C (400 mg) was added. The reaction mixture was stirred at room temperature under hydrogen for 16 hours. The reaction mixture was filtered and concentrated to afford 2.0 g of a yellow solid, yield 61.4%. MS (ESI) m / z: 400.2 [M+H]+. The following intermediates were prepared according to the synthetic route and methods described for Step 1: Synthesis of 2-azido-4-chloro-5-nitrobenzaldehyde Sodium azide (2.52 g, 38.8 mmol) was added to a solution of 4-chloro-2-fluoro-5-nitrobenzaldehyde (7.9 g, 38.8 mmol) in DMSO (50 mL). The mixture was stirred at 30°C for 1 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was washed with water, dried over Na2SO4, filtered, and concentrated. The residue was triturated with (PE / EA), filtered to afford 5.0 g of a yellow solid, yield 56.9%. Step 2: Synthesis of 2-azido-5-nitro-4-(piperidin-1-yl)benzaldehyde Piperidine (5.1 g, 59.7 mmol) was added to a solution of 2-azido-4-chloro-5-nitrobenzaldehyde (4.5 g, 19.9 mmol) in DMSO (100 mL). The mixture was stirred at 50°C for 3 h. The reaction mixture was poured into water and extracted with dichloromethane. The organic phase was washed with water, dried over NazSO^ filtered, and concentrated to afford 5.2 g of a brown solid, yield 94.9%. MS (ESI) m / z: 276.1 [M+H]+. Step 3: Synthesis of tert-butyl 4-(5-nitro-6-(piperidin-1-yl)-2H-indazol-2-yl)piperidine-1-carboxylate A solution of 2-azido-5-nitro-4-(piperidin-1-yl)benzaldehyde (5.2 g, 18.89 mmol), tert-butyl 4-aminopiperidine-1-carboxylate (3.78 g, 18.89 mmol), and trimethyl orthoformate (6.0 g, 56.67 mmol) in DCM (100 mL) was stirred at room temperature overnight. The reaction mixture was concentrated and purified by column chromatography to afford the title compound 3.5 g as a yellow solid, yield 43.2%. MS (ESI) m / z: 430.2 [M+H]+. Step 4: Synthesis of tert-butyl 4-(5-amino-6-(piperidin-1-yl)-2H-indazol-2-yl)piperidine-1-carboxylate Pd / C      (0.2      g)      was      added      to      a      solution      of      tert-butyl 4-(5-nitro-6-(piperidin-1-yl)-2H-indazol-2-yl)piperidine-1-carboxylate (1.40 g, 3.26 mmol) in methanol (15 mL). The mixture was purged with hydrogen and stirred at room temperature overnight. The reaction mixture was filtered and concentrated to afford the title compound (1.15 g, gray solid, yield 88%). MS (ESI) m / z: 400.3 [M+H]+. 'H-NMR (400 MHz, CDCb) 5: 7.62 (s, 1H), 7.25 (s, 1H), 6.80 (s, 1H), 4.47-4.28 (m, 5H), 2.91-2.85 (m, 6H), 2.19-2.03 (m, 4H), 1.79-1.61 (m, 6H), 1.45 (s, 9H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate C5: C10 boci / y nh2 430.3 —N / ° C11 BocN H z ^NH2 ^N'A -OH 402.2 C12 BocN )—N  J /    ' <*L '  N^\ 418.3 C13 Boel / / H z OH 416.3 C14 BocN^ — /   N"^ NH \^\o- 2 347.2 C15 Boel / o z 5^NH2 387.2 C16 \ r HN —< n z / ^ / NH2 328.2 C17 0 \ ■\ V- N \ J 'n^ ^.nh2 313.2 C18 h2n z OH 329.2 Synthesis of Intermediate C19 Step 1: tert-Butyl 4-(6-chloro-5-nitro-2H-indazol-2-yl)piperidine-1-carboxylate A solution of 2-azido-4-chloro-5-nitrobenzaldehyde in DCM (100 mL) and toluene (200 mL), with tert-butyl 4-aminopiperidine-1-carboxylate (8.84 g, 44.13 mmol) and trimethyl orthoformate (14.05 g, 132.39 mmol), was stirred at room temperature for 3 hours. The reaction mixture was concentrated, and the residue was purified by column chromatography to afford 12.1 g of a yellow solid, yield 72.0%. MS (ESI) m / z: 325.0 [M-56+H]+. Step 2: tert-Butyl 4-(5-nitro-6-phenyl-2H-indazol-2-yl)piperidine-1-carboxylate tert-Butyl 4-(6-chloro-5-nitro-2H-indazol-2-yl)piperidine-1-carboxylate (12.0 g, 31.51 mmol) was dissolved in toluene (210 mL), then phenylboronic acid (19.21 g, 157.56 mmol), potassium carbonate (34.84 g, 252.10 mmol), palladium(II) acetate (2.4 g), and water (150 mL) were added. The reaction mixture was stirred at 100°C for 16 hours. Water was added to quench, the mixture was extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford the title compound 7.0 g as an orange solid, yield 52.6%. MS (ESI) m / z: 423.2 [M+H]+. Step 3: tert-Butyl 4-(5-amino-6-phenyl-2H-indazol-2-yl)piperidine-1-carboxylate tert-Butyl 4-(5-nitro-6-phenyl-2H-indazol-2-yl)piperidine-1-carboxylate (3.0 g, 7.10 mmol) was dissolved in methanol (60 mL), then Pd / C (400 mg) was added. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered and concentrated to afford 2.4 g of a white solid, yield 85.9%. MS (ESI) m / z: 393.2 [M+H]+. ‘H-NMR (400 MHz, CDCb) 5: 7.71 (s, 1H), 7.50-7.36 (m, 6H), 6.86 (s, 1H), 4.544.46 (m, 1H), 4.30 (s, 2H), 3.59-3.48 (m, 2H), 2.95-2.90 (m, 2H), 2.23-2.20 (m, 2H), 2.12-2.02 (m, 2H), 1.48 (s, 9H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate C19: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ C20 .---- NH2 BocHN"' / / “N     T 407.2 C21 / --V               NH2 BocHN—(   )—N   | T X N \ 411.2 C22 / —\ BocN >—N ] T \-- / X ,N \ 397.2 C23 / --\ NH2 BocN M \--- / 411.2 C24 / \ BocN VN ^c^F 411.2 C25 BocHN" (   )— N J | F 425.2 Synthesis of Intermediate C26 C26 Step 1: Synthesis of methyl 4-methyl-6-nitro-[1,1‘-biphenyl]-3-carboxylate Methyl 5-chloro-2-methyl-4-nitrobenzoate (5.0 g, 21.78 mmol) was dissolved in 1,4-dioxane (100 mL), then water (20 mL), phenylboronic acid (5.31 g, 43.55 mmol), potassium carbonate (9.03 g, 65.33 mmol), and Pd(dppf)Ch (700 mg) were added. The mixture was heated to 100°C under nitrogen protection and stirred for 16 hours. The reaction mixture was poured into water and extracted with dichloromethane. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford 4.2 g of a yellow solid, yield 72.8%. Step 2: Synthesis of methyl 4-(bromomethyl)-6-nitro-[1,1‘-biphenyl]-3-carboxylate Methyl 4-methyl-6-nitro-[1,1‘-biphenyl]-3-carboxylate (4.2 g, 15.48 mmol) was dissolved in carbon tetrachloride (80 mL), then N-bromosuccinimide (2.76 g, 15.48 mmol) and azobisisobutyronitrile (500 mg) were added. The reaction mixture was stirred at 80°C for 16 hours. The reaction mixture was poured into water and extracted with dichloromethane. The organic phase was dried over N2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford the title compound 2.9 g as a yellow oil, yield 52.2%. Step 3: Synthesis of tert-butyl 4-(5-nitro-1-oxo-6-phenylisoindolin-2-yl)piperidine-1-carboxylate Methyl 4-(bromomethyl)-6-nitro-[1,1‘-biphenyl]-3-carboxylate (2.9 g, 8.28 mmol) was dissolved in methanol (50 mL), then tert-butyl 4-aminopiperidine-1-carboxylate (1.99 g, 9.94 mmol) and N,N-diisopropylethylamine (2.14 g, 16.56 mmol) were added. The reaction mixture was stirred at 60°C for 16 hours. The reaction mixture was poured into water and extracted with dichloromethane. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford 3.1 g of a yellow solid, yield 85.6%. MS (ESI) m / z: 382.1 [M-56+H]+. Step 4: Synthesis of tert-butyl 4-(5-amino-1-oxo-6-phenylisoindolin-2-yl)piperidine-1-carboxylate tert-Butyl 4-(5-nitro-1-oxo-6-phenylisoindolin-2-yl)piperidine-1-carboxylate (3.0 g, 6.86 mmol) was dissolved in ethyl acetate (60 mL), then Pd / C (700 mg) was added. The mixture was purged with hydrogen and stirred at room temperature for 4 hours. The reaction mixture was filtered and concentrated to afford 2.1 g of a white solid, yield 75.2%. MS (ESI) m / z: 352.2 [M-56+H]+. ‘H-NMR (400 MHz, CDCb) 5: 7.61 (s, 1H), 7.477.35 (m, 5H), 6.80 (s, 1H), 4.40-4.36 (m, 1H), 4.26 (s, 4H), 2.89-2.83 (m, 2H), 1.83-1.80 (m, 2H), 1.67-1.64 (m, 2H), 1.48 (s, 9H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate C26: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ C27 r~\ BocN y- N        1 O 415.3 C28 __             nh2 BocHN— / / \ JL 422.2 Synthesis of Intermediate C29 Step 1: 5-Chlorooxazolo[4,5-b]pyridine-2-thiol 2-Amino-6-chloropyridin-3-ol (50.0 g, 347.2 mmol) was dissolved in pyridine (400 mL), then potassium O-ethyldithiocarbonate (83.5 g, 520.8 mmol) was added. The reaction mixture was stirred at 120°C for 8 hours. The reaction mixture was concentrated, diluted with water, and pH was adjusted to 2. The mixture was filtered, and the solid was dried under reduced pressure to afford 44.0 g of a yellow solid, yield 67.9%. MS (ESI) m / z: 187.0 [M+H]+. Step 2: Synthesis of tert-butyl 4-(5-chlorooxazolo[4,5-b]pyridin-2-yl)piperazine-1-carboxylate 5-Chlorooxazolo[4,5-b]pyridine-2-thiol (38.0 g, 203.6 mmol) was dissolved in xylene (200 mL), then tert-butyl piperazine-1-carboxylate (41.7 g, 223.98 mmol) and N,N-diisopropylethylamine (52.6 g, 407.2 mmol) were added. The reaction mixture was stirred at 120°C for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography and dried under reduced pressure to afford 44.0 g of a white solid, yield 63.7%. MS (ESI) m / z: 339.1 [M+H]+. Step 3: 5-Chloro-6-nitro-2-(piperazin-1-yl)oxazolo[4,5-b]pyridine tert-Butyl 4-(5-chlorooxazolo[4,5-b]pyridin-2-yl)piperazine-1-carboxylate (22.3 g, 65.8 mmol) was dissolved in concentrated sulfuric acid (100 mL), then KNOs (26.6 g, 263.3 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into ice water, and sodium bicarbonate was added to adjust pH to 8, then used directly in the next step. Step 4: Synthesis of tert-butyl 4-(5-chloro-6-nitrooxazolo[4,5-b]pyridin-2-yl)piperazine-1-carboxylate 5-Chloro-6-nitro-2-(piperazin-1-yl)oxazolo[4,5-b]pyridine (21.3 g, 75.0 mmol) was dissolved in dichloromethane (100 mL), then di-tert-butyl dicarbonate (32.78 g, 150.17 mmol) was added. The reaction mixture was stirred at room temperature for half an hour. The reaction mixture was filtered, and the filtrate was extracted with dichloromethane. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford the title compound 20 g as a yellow solid, yield 71.4%. MS (ESI) m / z: 384.1 [M+H]+. Step                   5:                   Synthesis                   of                   (S)-tert-butyl 4-(5-(3-hydroxypyrrolidin-1-yl)-6-nitrooxazolo[4,5-b]pyridin-2-yl)piperazine-1-carboxylate tert-Butyl 4-(5-chloro-6-nitrooxazolo[4,5-b]pyridin-2-yl)piperazine-1-carboxylate (10.0 g, 26.06 mmol) was dissolved in tetrahydrofuran (200 mL), then (S)-pyrrolidin-3-ol (4.54 g, 52.11 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with dichloromethane. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford 9.0 g of a yellow solid, yield 79.5%. MS (ESI) m / z: 435.2 [M+H]+. Step                   6:                   Synthesis                   of                   (S)-tert-butyl 4-(6-amino-5-(3-hydroxypyrrolidin-1-yl)oxazolo[4,5-b]pyridin-2-yl)piperazine-1-carboxylate (S)-tert-Butyl 4-(5-(3-hydroxypyrrolidin-1-yl)-6-nitrooxazolo[4,5-b]pyridin-2-yl)piperazine-1-carboxylate (9.0 g, 20.72 mmol) was dissolved in ethyl acetate (200 mL), then palladium on carbon (1.5 g) was added. The reaction mixture was stirred at room temperature under hydrogen atmosphere for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated to afford 6.5 g of a solid, yield 77.6%. MS (ESI) m / z: 405.2 [M+H]+. The following intermediates were prepared according to the synthetic route and methods described for Intermediate C29: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ C30 O^^ / NH2 BocN         1 T L^o 405.2 C31 / —\          nh2 BocN N—J T x—' n^n^n^ L^X^oh 433.2 C32 / -\  O_^<NH2 BocN N—J T \ /     N          k| —*\ N y-OH 404.2 C33 / —\          nh2 BocN N^< 1 T \- /  N-^^s^n'^ ^-° 404.2 Synthesis of Intermediate C34 C34 Step 1: Synthesis of 5-nitro-6-(piperidin-1-yl)-2-(piperidin-4-yl)-2H-indazole hydrochloride 4 M HCl in dioxane (20 mL) was added to a solution of   tert-butyl 4-(5-nitro-6-(piperidin-1-yl)-2H-indazol-2-yl)piperidine-1-carboxylate (3.5 g, 8.09 mmol) in dichloromethane (40 mL). The mixture was stirred at room temperature overnight. The reaction mixture was concentrated to afford the title compound. MS (ESI) m / z: 330.2 [M+H]+. Step                            2:                            Synthesis                            of N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(4-((4-(5-nitro-6-(piperidin-1-yl)-2H-indazol-2-yl)piperidin-1-yl)methy l)piperidin-1-yl)benzamide N-(2,6-Dioxopiperidin-3-yl)-2-fluoro-4-(4-formylpiperidin-1-yl)benzamide (2.0 g, 5.54 mmol) was added to a solution of 5-nitro-6-(piperidin-1-yl)-2-(piperidin-4-yl)-2H-indazole (1.66 g, 5.04 mmol) in N,N-dimethylacetamide (40 mL). Glacial acetic acid (0.58 mL, 10.08 mmol) was added dropwise, and the mixture was stirred at room temperature for 5 hours. Sodium triacetoxyborohydride (2.14 g, 10.08 mmol) was then added, and the mixture was stirred for 2 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford 3.02 g of a red-brown solid, yield 88.8%. MS (ESI) m / z = 675.3 [M+H]+. Step                            3:                            Synthesis                            of 4-(4-((4-(5-amino-6-(piperidin-1-yl)-2H-indazol-2-yl)piperidin-1-yl)methyl)piperidin-1-yl)-N-(2,6-dioxopiperi din-3-yl)-2-fluorobenzamide N-(2,6-Dioxopiperidin-3-yl)-2-fluoro-4-(4-((4-(5-nitro-6-(piperidin-1-yl)-2H-indazol-2-yl)piperidin-1-yl) methyl)piperidin-1-yl)benzamide (1.51 g, 2.24 mmol) was dissolved in methanol (30 mL), then 5% Pd / C (150 mg) was added. The mixture was purged with hydrogen three times and stirred at room temperature for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated to afford 1.23 g of a gray-brown solid, yield 85.4%. MS (ESI) m / z = 645.4 [M+H]+. The following intermediates were prepared according to the synthetic route and methods described for C42 645.4 Synthesis of Intermediate C43 C43 Step 1: Synthesis of 8-bromoimidazo[1,2-c]pyrimidin-5(6H)-one 4-Amino-5-bromopyrimidin-2(1H)-one (10.0 g, 52.63 mmol) was dissolved in water (200 mL), then sodium acetate (12.95 g, 157.89 mmol) and 2-chloroacetaldehyde (40% aqueous solution) (20.66 g, 105.26 mmol) were added. The mixture was stirred at 80°C for 12 h. Water was added to quench, the mixture was extracted with ethyl acetate, the organic phase was concentrated and purified by column chromatography to afford 8.0 g of a pale yellow solid, yield 71.0%. MS (ESI) m / z: 214.1 [M+H]+. Step 2: Synthesis of methyl 5-oxo-5,6-dihydroimidazo[1,2-c]pyrimidine-8-carboxylate 8-Bromoimidazo[1,2-c]pyrimidin-5(6H)-one (4 g, 18.8 mmol) was dissolved in methanol (50 mL), then triethylamine (6.45 g, 63.8 mmol) and Pd(dppf)Ch (1.2 g) were added. The mixture was stirred at 100°C under carbon monoxide atmosphere for 18 h. The reaction mixture was concentrated and purified by column chromatography to afford the title compound 2.5 g as a light red solid, yield 69.1%. MS (ESI) m / z: 194.1 [M+H]+. Step 3: Synthesis of 5-oxo-5,6-dihydroimidazo[1,2-c]pyrimidine-8-carboxylic acid Methyl 5-oxo-5,6-dihydroimidazo[1,2-c]pyrimidine-8-carboxylate (1 g, 5.18 mmol) was dissolved in water (10 mL) and methanol (10 mL), then lithium hydroxide monohydrate (497 mg, 20.7 mmol) was added. The mixture was stirred at 50°C for 6 hours. The reaction mixture was concentrated, 2 M hydrochloric acid was added to adjust pH to approximately 4, and the mixture was stirred until solid precipitated. The mixture was filtered and concentrated to afford 720 mg of a pale yellow solid, yield 77.6%. MS (ESI) m / z: 180.0 [M+H]+. 'H-NMR (400 MHz, DMSO) 5: 8.05 (s, 1H), 7.84 (d, J = 1.6 Hz, 1H), 7.47 (d, J = 1.6 Hz, 1H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate C43: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ C44 / / \      nh2 ° n=n 141.0 C45 z z o T 181.0 C46 O^O H N^N ii 1 126.0 C47 o T 181.0 C48 <^N'N \ / v-ci N 0=\ OH 198.0 Synthesis of Intermediate C49 0 C49 Step 1: Synthesis of ethyl 5-methylimidazo[1,2-a]pyrimidine-7-carboxylate Ethyl 2-amino-6-methylpyrimidine-4-carboxylate (7.0 g, 38.63 mmol) was dissolved in DCM (150 mL), then 40% chloroacetaldehyde solution (11.38 g, 57.95 mmol) was added. The reaction mixture was stirred at 90°C for 4 hours. The reaction mixture was poured into water, extracted with dichloromethane, and the organic phase was concentrated. The residue was purified by column chromatography to afford the title compound 900 mg as a white solid, yield 9.3%. MS (ESI) m / z: 206.1 [M+H]+. Step 2: Synthesis of 5-methylimidazo[1,2-a]pyrimidine-7-carboxylic acid Ethyl 5-methylimidazo[1,2-a]pyrimidine-7-carboxylate (800 mg, 3.90 mmol) was dissolved in THF (20 mL) and water (5 mL), then lithium hydroxide monohydrate (491 mg, 11.7 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, water was added, and 3 M citric acid was slowly added until pH = 5. The mixture was filtered, and the filter cake was dried to afford 435 mg of a white solid, yield 63.0%. MS (ESI) m / z: 178.1 [M+H]+. ‘H-NMR (400 MHz, DMSO) 5: 13.37 (brs, 1H), 8.08 (s, 1H), 8.01 (s, 1H), 7.55 (s, 1H), 2.76 (s, 3H). The following intermediates were prepared according to the synthetic route and methods described for Intermediate C49: Intermediate Intermediate Structure MS (ESI) m / z [M+H]+ C50 X o Vo V 178.1 Synthesis of Intermediate C51 Br Step 1: Ethyl 7-(pyridin-4-yl)thieno[2,3-b]pyrazine-6-carboxylate Ethyl 7-bromothieno[2,3-b]pyrazine-6-carboxylate (4.0 g, 13.93 mmol) in 1,4-dioxane (100 mL) and water (20 mL), with pyridin-4-ylboronic acid (3.42 g, 27.86 mmol), sodium bicarbonate (3.51 g, 41.79 mmol), and PdCh(dppf) (0.5 g), was stirred at 80°C under nitrogen for 16 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was concentrated and purified by column chromatography to afford 1.8 g of a white solid, yield 45.3%. MS (ESI) m / z: 286.0 [M+H]+. Step 2: 7-(Pyridin-4-yl)thieno[2,3-b]pyrazine-6-carboxylic acid Ethyl 7-(pyridin-4-yl)thieno[2,3-b]pyrazine-6-carboxylate (1.8 g, 6.31 mmol) was dissolved in methanol (50 mL), then sodium hydroxide (0.5 g, 12.62 mmol) and water (5 mL) were added. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated, 2 M HCl was added to adjust pH = 5, solid precipitated, the mixture was filtered, and the filter cake was dried to afford 1.3 g of a white solid, yield 80.1%. MS (ESI) m / z: 258.0 [M+H]+. 'H-NMR (400 MHz, DMSO) 5: 14.11 (brs, 1H), 8.85-8.83 (m, 2H), 8.69-8.67 (m, 2H), 7.55-7.53 (m, 2H). The following intermediates were prepared according to the synthetic route and methods described for Step 1: Synthesis of methyl imidazo[1,2-b]pyridazine-7-carboxylate Methyl 6-aminopyridazine-4-carboxylate (730 mg, 4.77 mmol) was dissolved in isopropanol (30 mL), then 40% chloroacetaldehyde (2.81 g, 14.31 mmol) was added. The reaction mixture was stirred at 100°C for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford 600 mg of a white solid, yield 71.1%. MS (ESI) m / z: 178.1 [M+H]+. Step 2: Synthesis of imidazo[1,2-b]pyridazine-7-carboxylic acid Methyl imidazo[1,2-b]pyridazine-7-carboxylate (600 mg, 3.39 mmol) was dissolved in THF (20 mL) and water (5 mL), then LiOH^O (427 mg, 10.16 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated, 3 M hydrochloric acid was added dropwise to pH = 5, the mixture was filtered, and the filter cake was dried to afford 20 mg of a white solid, yield 76.1%. MS (ESI) m / z: 164.1 [M+H]+. 'H-NMR (400 MHz, DMSO) 5: 8.87 (s, 1H), 8.55 (s, 1H), 8.51 (s, 1H), 8.01 (s, 1H). Synthesis of Intermediate C55 Step 1: Synthesis of methyl 6-((4-methoxybenzyl)amino)pyridazine-4-carboxylate Methyl 6-chloropyridazine-4-carboxylate (5.0 g, 28.97 mmol) was dissolved in DMSO (50 mL), then (4-methoxyphenyl)methanamine (4.77 g, 34.77 mmol) and N,N-diisopropylethylamine (11.23 g, 86.92 mmol) were added. The reaction mixture was stirred at 120°C for 2.5 hours. The reaction mixture was filtered, and the filtrate was poured into water and extracted with ethyl acetate. The organic phase was dried over N2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford the title compound 2.3 g as a yellow solid, yield 31.6%. MS (ESI) m / z: 274.1 [M+H]+. Step 2: Synthesis of methyl 6-aminopyridazine-4-carboxylate Methyl 6-((4-methoxybenzyl)amino)pyridazine-4-carboxylate (2.3 g, 8.42 mmol) was dissolved in trifluoroacetic acid (40 mL). The reaction mixture was stirred at 80°C for 16 hours. The reaction mixture was concentrated, poured into sodium bicarbonate aqueous solution, and extracted with dichloromethane. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford 730 mg of a yellow solid, yield 56.7%. MS (ESI) m / z: 154.1 [M+H]+. Step 3: Synthesis of 6-aminopyridazine-4-carboxylic acid Methyl 6-aminopyridazine-4-carboxylate (1.05 g, 6.53 mmol) was dissolved in concentrated hydrochloric acid (20 mL). The reaction mixture was stirred at 100°C for 16 hours. The reaction mixture was concentrated to afford 906 mg of a brown solid, yield 94.9%. MS (ESI) m / z: 140.1 [M+H]+. HNMR (400 MHz, DMSO) 5: 9.00 (br s, 2H), 8.66 (s, 1H), 7.98 (s, 1H). Synthesis of Intermediate C56 nh2 C56 nh2 Step 1: Synthesis of 2-chloro-5-fluoro-4-(furan-2-yl)pyrimidine 2,4-Dichloro-5-fluoropyrimidine (10.0 g, 59.8 mmol) was dissolved in 1,4-dioxane (120 mL) and water (30 mL), then furan-2-ylboronic acid (8.0 g, 71.8 mmol), sodium carbonate (19.0 g, 179.4 mmol), and tris(dibenzylideneacetone)dipalladium (1.0 g) were added. The mixture was stirred at 80°C for 24 h. The reaction mixture was quenched with water, extracted with ethyl acetate, and the organic phase was purified by column chromatography to afford 10.2 g of a yellow solid, yield 85.7%. MS (ESI) m / z: 199.1 [M+H]+. Step 2: Synthesis of 5-fluoro-4-(furan-2-yl)pyrimidin-2-amine 2-Chloro-5-fluoro-4-(furan-2-yl)pyrimidine (5.0 g, 25.1 mmol) was dissolved in methanolic ammonia (7 M, 50 mL). The reaction mixture was stirred in a sealed vessel at 90°C for 60 hours. The organic phase was purified by column chromatography to afford the title compound 1.8 g as a yellow solid, yield 40.0%. MS (ESI) m / z: 180.1 [M+H]+. Step 3: Synthesis of 2-amino-5-fluoropyrimidine-4-carboxylic acid 5-Fluoro-4-(furan-2-yl)pyrimidin-2-amine (1.8 g, 10.0 mmol) was dissolved in acetonitrile (15 mL) and water (15 mL), then potassium permanganate (9.5 g, 60.0 mmol) was added. The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was filtered, and the filtrate was purified to afford the title compound 1.2 g as a white solid, yield 76.0%. MS (ESI) m / z: 158.1 [M+H]+. ‘H-NMR (400 MHz, DMSO-d,) 5: 7.98-7.96 (m, 1H), 6.19 (brs, 2H). Synthesis of Intermediate C57 Step 1: Synthesis of methyl 2-chloro-3-formamidoisonicotinate Formic acid (2.96 g, 64.31 mmol) and acetic anhydride (3.28 g, 32.15 mmol) were added to a flask and stirred at 50°C for one hour. Methyl 3-amino-2-chloroisonicotinate (3.0 g, 16.08 mmol) was dissolved in dichloromethane (100 mL) and added to the reaction mixture under an ice bath. The reaction mixture was stirred at 40°C for 18 hours. The reaction mixture was poured into sodium bicarbonate solution and extracted with dichloromethane. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography to afford 3.0 g of a white solid, yield 86.9%. MS (ESI) m / z: 215.1 [M+H]+. Step 2: Synthesis of methyl thiazolo[5,4-b]pyridine-7-carboxylate Methyl 2-chloro-3-formamidoisonicotinate (3.3 g, 15.37 mmol) was dissolved in tetrahydrofuran (100 mL), then Lawesson's reagent (6.22 g, 15.37 mmol) was added. The reaction mixture was stirred at 80°C for 16 hours. The reaction mixture was poured into sodium bicarbonate aqueous solution and extracted with dichloromethane. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by reverse-phase column chromatography to afford the title compound 1.2 g as a pale yellow solid, yield 44.2%. MS (ESI) m / z: 195.0 [M+H]+. Step 3: Synthesis of thiazolo[5,4-b]pyridine-7-carboxylic acid Methyl thiazolo[5,4-b]pyridine-7-carboxylate (1.2 g, 6.18 mmol) was dissolved in tetrahydrofuran (20 mL) and water (5 mL), then lithium hydroxide monohydrate (777 mg, 18.54 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated, 3 M hydrochloric acid was slowly added to pH = 5, the mixture was filtered, and the filter cake was dried to afford 1.03 g of a yellow solid, yield 92.5%. MS (ESI) m / z: 181.1 [M+H]+. 'H-NMR (400 MHz, DMSO) 5: 13.82 (brs, 1H), 9.68 (s, 1H), 8.81 (d, J = 4.8 Hz, 1H), 7.87 (d, J = 4.8 Hz, 1H). Synthesis of Intermediate C58 Step 1: Synthesis of 7-bromothiazolo[5,4-c]pyridine 7-Bromothiazolo[5,4-c]pyridin-2-amine (2.2 g, 9.6 mmol) was dissolved in tetrahydrofuran (200 mL), then tert-butyl nitrite (5.6 g, 48.0 mmol) was added. The reaction mixture was stirred at 90°C for 16 hours. The reaction mixture was cooled, extracted with ethyl acetate, and the organic phase was concentrated and purified by column chromatography to afford 1.1 g of a yellow solid, yield 53.6%. MS (ESI) m / z: 215.0, 217.0 [M+H]+. Step 2: Synthesis of methyl thiazolo[5,4-c]pyridine-7-carboxylate 7-Bromothiazolo[5,4-c]pyridine (1.1 g, 5.1 mmol) was dissolved in methanol (20 mL), then triethylamine (1.6 g, 15.4 mmol) and Pd(dppf)Ch (187 mg, 0.26 mmol) were added. The reaction mixture was stirred at 100°C under CO atmosphere for 16 hours. The reaction mixture was concentrated, and the residue was purified by column chromatography to afford 780 mg of a pale yellow solid, yield 75%. MS (ESI) m / z: 195.1 [M+H]+. Step 3: Synthesis of thiazolo[5,4-c]pyridine-7-carboxylic acid Methyl thiazolo[5,4-c]pyridine-7-carboxylate (500 mg, 2.56 mmol) was dissolved in tetrahydrofuran (10 mL) and water (5 mL), then lithium hydroxide monohydrate (420 mg, 10.2 mmol) was added at 0°C. The reaction mixture was stirred at 0°C for 1 h. 3 M citric acid was added dropwise to pH = 4, the mixture was extracted with ethyl acetate, and the organic phase was concentrated. The crude product was purified by reverse-phase column chromatography to afford 100 mg of a white solid, yield 21%. MS (ESI) m / z: 181.1 [M+H]+. 'H-NMR (400 MHz, DMSO) 5: 13.45 (br, 1H), 9.80 (s, 1H), 9.64 (s, 1H), 9.02 (s, 1H). Synthesis of Intermediate C59 Step 1: Synthesis of ethyl 1-(2-methylpyridin-4-yl)-1H-pyrazole-4-carboxylate (1S,2S)-N1,N2-Dimethylcyclohexane-1,2-diamine (1.02 g, 7.1 mmol) was added to a mixture of ethyl 1H-pyrazole-4-carboxylate (5 g, 35.7 mmol), 4-bromo-2-methylpyridine (7.37 g, 42.8 mmol), copper(I) iodide (0.34 g, 1.7 mmol), and potassium carbonate (9.87 g, 71.4 mmol) in anhydrous toluene (100 mL). The mixture was purged with nitrogen, then heated to 110°C and stirred for 24 hours. Water was added, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography to afford 2.6 g of a white solid, yield 31.4%. MS (ESI) m / z = 232.1 [M+H]+. Step 2: Synthesis of 1-(2-methylpyridin-4-yl)-1H-pyrazole-4-carboxylic acid A solution of lithium hydroxide monohydrate (1.89 g, 44.97 mmol) in water (30 mL) was slowly added to a solution of ethyl 1-(2-methylpyridin-4-yl)-1H-pyrazole-4-carboxylate (2.6 g, 11.24 mmol) in tetrahydrofuran (30 mL). The mixture was heated to 50°C and stirred for 1 h. The mixture was concentrated, diluted with water, and dilute hydrochloric acid solution (1 mol / L) was added dropwise until precipitation occurred. The filter cake was washed with water and dried to afford 2.05 g of a pale pink solid, yield 88.8%. MS (ESI) m / z = 204.2 [M+H]+. 'H-NMR (400 MHz, DMSO) 5 12.81 (s, 1H), 9.21 (s, 1H), 8.53 (d, J = 5.6 Hz, 1H), 8.16 (s, 1H), 7.87 (d, J = 1.8 Hz, 1H), 7.76 (dd, J = 5.5, 2.0 Hz, 1H), 2.53 (s, 3H). The following intermediates were prepared according to the synthetic route and methods described for C61 Step 1: Methyl pyrrolo[1,2-a]pyrimidine-8-carboxylate To a solution of methyl 2-(pyrimidin-2-yl)acetate (1.8 g, 11.8 mmol) in acetone (30 mL), sodium bicarbonate (4.1 g, 48.4 mmol), lithium bromide (1.0 g, 11.8 mmol), and 2-chloroacetaldehyde (4.6 g, 59.1 mmol) (40% aqueous solution) were added. The mixture was stirred at 60°C for 16 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic phase was purified by silica gel column chromatography to afford 1.9 g of a yellow oil, yield 91.4%. Step 2: Pyrrolo[1,2-a]pyrimidine-8-carboxylic acid Methyl pyrrolo[1,2-a]pyrimidine-8-carboxylate (1.9 g, 10.8 mmol) was dissolved in tetrahydrofuran (20 mL), then lithium hydroxide monohydrate (2.3 g, 53.9 mmol) and water (5 mL) were added. The reaction mixture was stirred at room temperature until the reaction was complete. 2 M hydrochloric acid was added to adjust pH to approximately 4, the mixture was extracted with ethyl acetate, the organic phase was dried, filtered, and concentrated to afford 850 mg of a yellow solid, yield 46.8%. MS (ESI) m / z: 161.1 [M-H]_. ‘H-NMR (400 MHz, DMSO) 5: 11.77 (s, 1H), 8.87-8.85 (m, 1H), 8.43-8.42 (m, 1H), 7.54-7.53 (m, 1H), 7.30-7.29 (m, 1H), 6.97-6.95 (m, 1H). General Synthetic Procedures General Synthetic Procedure A To a solution of the amine (1.0 equiv.) and carboxylic acid (1.0 equiv.) in DMF were sequentially added DIPEA (3.0 equiv.) and HATU (1.2 equiv.). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was then extracted with DCM. The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was further purified by preparative TLC (DCM:MeOH = 10:1) to afford the title compound. General Synthetic Procedure B To a solution of the amine (1.0 equiv.) and carboxylic acid (1.0 equiv.) in dry DMF were sequentially added DIPEA (3.0 equiv.) and T3P (1.5 equiv.). The reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was then extracted with DCM. The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was further purified by preparative TLC (DCM:MeOH = 10:1) to afford the title compound. General Synthetic Procedure C To a solution of the amine (1.0 equiv.) and carboxylic acid (1.0 equiv.) in dry DMF were sequentially added DIPEA (3.0 equiv.) and Py BOP (1.5 equiv.). The reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was then extracted with DCM. The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was further purified by preparative TLC (DCM:MeOH = 10:1) to afford the title compound. General Synthetic Procedure D To a solution of the amine (1.0 equiv.) and carboxylic acid (1.0 equiv.) in dry DMF were sequentially added DIPEA (3.0 equiv.) and EDCI (1.5 equiv.). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was then extracted with DCM. The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was further purified by preparative TLC (DCM:MeOH = 10:1) to afford the title compound. General Synthetic Procedure E Step 1: To a solution of amine intermediate C (1.0 equiv.) and carboxylic acid (1.0 equiv.) in DMF were sequentially added DIPEA (3.0 equiv.) and HATU (1.2 equiv.). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was then extracted with DCM. The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (methanol / dichloromethane, 0~10%) to afford the title compound. Step 2: Trifluoroacetic acid (10 mL) was added dropwise to a solution of the Step 1 product (1.0 equiv.) in dichloromethane (30 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated to afford the title compound, which was used directly in the next step without further purification. Step 3: Aldehyde intermediate B (1.1 equiv.) was added to a solution of the Step 2 amine compound (1.0 equiv.) in N,N-dimethylformamide (10 mL). The mixture was stirred at room temperature for 5 minutes, then triethylamine (2.0 equiv.) was added dropwise. The mixture was stirred at room temperature for 5 hours, then sodium triacetoxyborohydride (2.0 equiv.) was added in two portions. The mixture was stirred at room temperature for 16 hours and monitored by TLC until the reaction was complete. n-Butanol (15 mL) was added to dilute the reaction mixture, which was then washed with saturated aqueous NaCl (100 mL x 5). The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was further purified by preparative TLC (DCM:MeOH = 10:1) to afford the title compound. General Synthetic Procedure F Step 1: To a solution of amine intermediate C (1.0 equiv.) and carboxylic acid (1.0 equiv.) in DMF were sequentially added DIPEA (3.0 equiv.) and HATU (1.2 equiv.). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was then extracted with DCM. The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (methanol / dichloromethane, 0~10%) to afford the title compound. Step 2: The Step 1 product (1.0 equiv.) was dissolved in DMF, then Dess-Martin periodinane (1.5 equiv.) was added, and the mixture was stirred at room temperature until the reaction was complete. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The combined organic phases were dried over N2SO4, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (methanol / dichloromethane, 0~5%) to afford the title compound. Step 3: Aldehyde intermediate B (1.1 equiv.) was added to a solution of the Step 2 amine compound (1.0 equiv.) in N,N-dimethylformamide (10 mL). The mixture was stirred at room temperature for 5 minutes, then triethylamine (2.0 equiv.) was added dropwise. The mixture was stirred at room temperature for 5 hours, then sodium triacetoxyborohydride (2.0 equiv.) was added in two portions. The mixture was stirred at room temperature for 16 hours and monitored by TLC until the reaction was complete. n-Butanol (15 mL) was added to dilute the reaction mixture, which was then washed with saturated aqueous NaCl (100 mL x 5). The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was further purified by preparative TLC (DCM:MeOH = 10:1) to afford the title compound. General Synthetic Procedure G Step 1: To a solution of amine intermediate C (1.0 equiv.) and carboxylic acid (1.0 equiv.) in DMF were sequentially added DIPEA (3.0 equiv.) and HATU (1.2 equiv.). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was then extracted with DCM. The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (methanol / dichloromethane, 0~10%) to afford the title compound. Step 2: Trifluoroacetic acid (10 mL) was added dropwise to a solution of the Step 1 product (1.0 equiv.) in dichloromethane (30 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated to afford the title compound, which was used directly in the next step without further purification. Step 3: The Step 2 product (1.0 equiv.), carboxylic acid intermediate B (1.0 equiv.), DIPEA (3.0 equiv.), and HATU (1.2 equiv.) were dissolved in DMF. The reaction mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was then extracted with DCM. The combined organic phases were dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (methanol / dichloromethane, 0~10%) to afford the title compound. Example                          1:                          Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-4-carboxamide (Compound 1) Compound 1 was prepared from 7-azaindole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         2:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-6-carboxamide (Compound 2) Compound 2 was prepared from 1H-benzimidazole-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         3:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)isoquinoline-8-carboxamide (Compound 3) Compound 3 was prepared from 8-isoquinoline-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 800.4 Example                         4:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-5-carboxamide (Compound 4) Compound 4 was prepared from 7-azaindole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         5:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)quinoxaline-5-carboxamide (Compound 5) Compound 5 was prepared from quinoxaline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                         6:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)benzo[c][1,2,5]thiadiazole-4-carboxamide (Compound 6) Compound 6 was prepared from 2,1,3-benzothiadiazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 807.3 Example                         7:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 7) Compound 7 was prepared from 2-methyl-6-imidazo[2,1-a]pyridinecarboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 803.4 Example                         8:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)benzo[d]thiazole-7-carboxamide (Compound 8) Compound 8 was prepared from 7-carboxybenzothiazole as a starting material according to General Synthetic Method A. MS [M+H]+: 806.3 Example                         9:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxamide (Compound 9) Compound 9 was prepared from 1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 847.4 Example                         10:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 10) Compound 10 was prepared from 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 821.4 Example                         11:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 11) Compound 11 was prepared from 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 821.4 Example                         12:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide (Compound 12) Compound 12 was prepared from [1,2,4]triazolo[4,3-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 790.4 Example                         13:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (Compound 13) Compound 13 was prepared from [1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 790.4 Example                         14:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 14) Compound 14 was prepared from 1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 883.4 Example                         15:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-indole-5-carboxamide (Compound 15) Compound 15 was prepared from indole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 788.4 Example                         16:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-indole-4-carboxamide (Compound 16) Compound 16 was prepared from indole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 788.4 Example 17: Synthesis of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)quinoline-6-carboxamide (Compound 17) Compound 17 was prepared from quinoline-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 800.4 Example                         18:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)benzo[b]thiophene-3-carboxamide (Compound 18) Compound 18 was prepared from 1-benzothiophene-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 805.3 Example                         19:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-methyl-5-phenyl-1H-pyrazole-4-carboxamide (Compound 19) Compound 19 was prepared from 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 829.4 Example                         20:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)isoquinoline-5-carboxamide (Compound 20) Compound 20 was prepared from isoquinoline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 800.4 Example                         21:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-6-carboxamide (Compound 21) Compound 21 was prepared from imidazo[1,2-b]pyridazine-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 790.4 Example                         22:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1,5-naphthyridine-3-carboxamide (Compound 22) Compound 22 was prepared from 1,5-naphthyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                         23:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)quinoline-4-carboxamide (Compound 23) Compound 23 was prepared from quinoline-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 800.4 Example                         24:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-6-carboxamide (Compound 24) Compound 24 was prepared from imidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         25:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-7-carboxamide (Compound 25) Compound 25 was prepared from imidazo[1,2-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         26:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide (Compound 26) Compound 26 was prepared from 4H-thieno[3,2-b]pyrrole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 794.3 Example                         27:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)quinoline-5-carboxamide (Compound 27) Compound 27 was prepared from quinoline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 800.4 Example                         28:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,5-a]pyridine-8-carboxamide (Compound 28) Compound 28 was prepared from imidazol[1,5-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         29:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6 -(piperidin-1-yl)-2H-indazol-5-yl)-3H-imidazo[4,5-b]pyridine-5-carboxamide (Compound 29) Compound 29 was prepared from 3H-imidazolo[4,5-b]pyridine-5-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 802.4 Example                         30:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-2-methyl-1H-benzo[d]imidazole-5-carboxamide (Compound 30) Compound 30 was prepared from 2-methyl-1H-benzimidazole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 803.4 Example                         31:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-8-carboxamide (Compound 31) Compound 31 was prepared from imidazo[1,2-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 789.4 Example                         32:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-3-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 32) Compound 32 was prepared from 3-methylimidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 803.4 Example                         33:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-4-carboxamide (Compound 33) Compound 33 was prepared from benzimidazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         34:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-(3-methoxyphenyl)-1H-pyrazole-4-carboxamide (Compound 34) Compound 34 was prepared from 1-(3-methoxyphenyl)pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 845.4 Example                         35:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)benzo[c][1,2,5]thiadiazole-5-carboxamide (Compound 35) Compound 35 was prepared from 2,1,3-benzothiadiazole-5-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 807.3 Example                         36:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)thieno[3,2-d]pyrimidine-4-carboxamide (Compound 36) Compound 36 was prepared from thieno[3,2-d]pyrimidine-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 807.3 Example                         37:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)thieno[2,3-c]pyridine-2-carboxamide (Compound 37) Compound 37 was prepared from thiophene[2,3-c]pyridine-2-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 806.3 Example                         38:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-3-carboxamide (Compound 38) Compound 38 was prepared from 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 793.4 Example                         39:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (Compound 39) Compound 39 was prepared from pyrazolo[1,5-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         40:                         Synthesis                         of 4-amino-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide (Compound 40) Compound 40 was prepared from 4-aminothieno[3,2-d]pyrimidine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 822.3 Example                         41:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide (Compound 41) Compound 41 was prepared from 5-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 829.4 Example                         42:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-2-carboxamide (Compound 42) Compound 42 was prepared from imidazo[1,2-b]pyridazine-2-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 790.4 Example                         43:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyrazine-3-carboxamide (Compound 43) Compound 43 was prepared from imidazo[1,2-a]pyrazine-3-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 790.4 Example                         44:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-pyrrolo[3,2-c]pyridine-7-carboxamide (Compound 44) Compound 44 was prepared from 5-azaindole-7-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 789.4 Example                         45:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-b]pyridazine-3-carboxamide (Compound 45) Compound 45 was prepared from pyrazolo[1,5-b]pyridazine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 790.4 Example                         46:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-indole-6-carboxamide (Compound 46) Compound 46 was prepared from 6-indolecarboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 788.4 Example                         47:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (Compound 47) Compound 47 was prepared from pyrazolo[1,5-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         48:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-indole-7-carboxamide (Compound 48) Compound 48 was prepared from 7-indolecarboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 788.4 Example                         49:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,5-a]pyridine-8-carboxamide (Compound 49) Compound 49 was prepared from imidazolo[1,5-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 789.4 Example                         50:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-pyrrolo[2,3-c]pyridine-3-carboxamide (Compound 50) Compound 50 was prepared from 1H-pyrrolo[2,3-c]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 789.4 Example                         51:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-3H-imidazo[4,5-b]pyridine-7-carboxamide (Compound 51) Compound 51 was prepared from 3H-imidazolo[4,5-b]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 790.4 Example                         52:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine-4-carboxamide (Compound 52) Compound 52 was prepared from 7H-pyrrolo[2,3-d]pyrimidine-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 790.4 Example                         53:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide (Compound 53) Compound 53 was prepared from 3H-imidazolo[4,5-c]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 790.4 Example                         54:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-a]pyrimidine-6-carboxamide (Compound 54) Compound 54 was prepared from pyrazolo[1,5-a]pyrimidine-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 790.4 Example                         55:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridine-4-carboxamide (Compound 55) Compound 55 was prepared from 1H-pyrazolo[4,3-c]pyridine-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 790.4 Example                         56:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide (Compound 56) Compound 56 was prepared from imidazole[1,2-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 801.4 Example                         57:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-2-(2-methylpyridin-4-yl)thiazole-4-carboxamide (Compound 57) Compound 57 was prepared from 2-(2-methylpyridine-4-yl)thiazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 859.4 Example                         58:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-2-(pyrimidin-2-yl)oxazole-4-carboxamide (Compound 58) Compound 58 was prepared from 2-(pyrimidine-2-yl)oxazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 830.4 Example                         59:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-(pyrimidin-2-yl)-1H-imidazole-4-carboxamide (Compound 59) Compound 59 was prepared from 1-(pyrimidin-2-yl)-1H-imidazole-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 829.4 Example                         60:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4- yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxamide (Compound 60) Compound 60 was prepared from 1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 859.4 Example                         61:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)oxazole-4-carboxamide (Compound 61) Compound 61 was prepared from 2-(1-methyl-1H-pyrazole-4-yl)oxazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 832.4 Example                         62:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-(2-methylpyridin-4-yl)-1H-pyrazole-4-carboxamide (Compound 62) Compound 62 was prepared from 1-(2-methylpyridin-4-yl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 842.4 Example                         63:                         Synthesis                         of (S)-N-(2,6-dioxopiperidin-3-yl)-2-methoxy-4-(4-((4-(5-(4-phenoxybenzamido)-6-(piperidin-1-yl)-2H-indazol-2-yl)piperidin-1-yl)methyl)piperidin-1-yl)benzamide (Compound 63) Compound 63 was prepared from 4-phenoxybenzenecarboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 853.4 Example                         64:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-2-phenylthiazole-4-carboxamide (Compound 64) Compound 64 was prepared from 2-phenyl-1,3-thiazole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 844.4 Example                         65:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-(pyridin-3-yl)-1H-pyrazole-4-carboxamide (Compound 65) Compound 65 was prepared from 1-(pyridin-3-yl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 828.4 Example                         66:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4- yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)benzofuran-7-carboxamide (Compound 66) Compound 66 was prepared from benzofuran-7-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 801.4 Example                         67:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)benzofuran-3-carboxamide (Compound 67) Compound 67 was prepared from benzofuran-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                         68:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-carboxamide (Compound 68) Compound 68 was prepared from pyrazole[1,5-a] 4,5,6,7-tetrahydropyridine-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 805.4 Example                         69:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide (Compound 69) Compound 69 was prepared from 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 791.4 Example                         70:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydro-1H-indazole-3-carboxamide (Compound 70) Compound 70 was prepared from 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 805.4 Example                         71:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxamide   (Compound 71) Compound 71 was prepared from 1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 791.4 Example 72: Synthesis of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxamide (Compound 72) Compound 72 was prepared from 1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 805.4 Example                         73:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzo[d]thiazole-7-carboxamide (Compound 73) Compound 73 was prepared from 7-carboxybenzothiazole as a starting material according to General Synthetic Method A. MS [M+H]+: 800.3 Example                         74:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxamide (Compound 74) Compound 74 was prepared from 1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 841.4 Example                         75:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 75) Compound 75 was prepared from 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 815.4 Example                         76:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide (Compound 76) Compound 76 was prepared from 4H-thieno[3,2-b]pyrrole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 788.3 Example                         77:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)quinoline-4-carboxamide (Compound 77) Compound 77 was prepared from quinoline-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 794.4 Example                         78:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)quinoline-5-carboxamide (Compound 78) Compound 78 was prepared from quinoline-5-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 794.4 Example                         79:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-6-carboxamide (Compound 79) Compound 79 was prepared from imidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 783.4 Example                         80:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-7-carboxamide (Compound 80) Compound 80 was prepared from imidazo[1,2-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 783.4 Example                         81:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1,5-naphthyridine-3-carboxamide (Compound 81) Compound 81 was prepared from 1,5-naphthyridine-3-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 795.4 Example                         82:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-4-carboxamide (Compound 82) Compound 82 was prepared from 7-azaindole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 783.4 Example                         83:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)isoquinoline-8-carboxamide (Compound 83) Compound 83 was prepared from 8-isoquinoline-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 794.4 Example                         84:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)quinoxaline-5-carboxamide (Compound 84) Compound 84 was prepared from quinoxaline-5-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 795.4 Example                         85:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-5-carboxamide (Compound 85) Compound 85 was prepared from 7-azaindole-5-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 783.4 Example                         86:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 86) Compound 86 was prepared from 2-methyl-6-imidazo[2,1-a]pyridine carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 797.4 Example                         87:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzo[c][1,2,5]thiadiazole-4-carboxamide (Compound 87) Compound 87 was prepared from 2,1,3-benzothiadiazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.3 Example                         88:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide (Compound 88) Compound 88 was prepared from imidazole[1,2-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         89:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (Compound 89) Compound 89 was prepared from 4-azaindole-3-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 789.4 Example                         90:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-2-(2-methylpyridin-4-yl)thiazole-4-carboxamide (Compound 90) Compound 90 was prepared from 2-(2-methylpyridine-4-yl)thiazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 847.3 Example                         91:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-2-(pyrimidin-2-yl)oxazole-4-carboxamide (Compound 91) Compound 91 was prepared from 2-(pyrimidine-2-yl)oxazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 818.4 Example                         92:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-(pyrimidin-2-yl)-1H-imidazole-4-carboxamide (Compound 92) Compound 92 was prepared from 1-(pyrimidin-2-yl)-1H-imidazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 817.4 Example                         93:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)oxazole-4-carboxamide (Compound 93) Compound 93 was prepared from 2-(1-methyl-1H-pyrazole-4-yl)oxazole-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 820.4 Example                         94:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-(2-methylpyridin-4-yl)-1H-pyrazole-4-carboxamide (Compound 94) Compound 94 was prepared from 1-(2-methylpyridin-4-yl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 830.4 Example                         95:                         Synthesis                         of N-(2,6-dioxopiperidin-3-yl)-2-fluoro-4-(4-((4-(5-(4-phenoxybenzamido)-6-(piperidin-1-yl)-2H-indazol-2-yl)pi peridin-1-yl)methyl)piperidin-1-yl)benzamide (Compound 95) Compound 95 was prepared from 4-phenoxybenzenecarboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 841.4 Example                         96:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-2-phenylthiazole-4-carboxamide (Compound 96) Compound 96 was prepared from 2-phenyl-1,3-thiazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 832.3 Example                         97:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-(pyridin-3-yl)-1H-pyrazole-4-carboxamide (Compound 97) Compound 97 was prepared from 1-(pyridin-3-yl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 816.4 Example                         98:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)benzofuran-7-carboxamide (Compound 98) Compound 98 was prepared from benzofuran-7-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 789.4 Example                         99:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)benzofuran-3-carboxamide (Compound 99) Compound 99 was prepared from benzofuran-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 789.4 Example                         100:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-carboxamide (Compound 100) Compound 100 was prepared from pyrazole[1,5-a] 4,5,6,7-tetrahydropyridine-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 793.4 Example                         101:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide (Compound 101) Compound 101 was prepared from 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 779.4 Example                         102:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydro-1H-indazole-3-carboxamide (Compound 102) Compound 102 was prepared from 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 793.4 N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxamide (Compound 103) Compound 103 was prepared from 1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 779.4 Example                         104:                         Synthesis                         of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)-1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxamide (Compound 104) Compound 104 was prepared from 1-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 793.4 Example                         105:                         Synthesis                        of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)benzofuran-4-carboxamide (Compound 105) Compound 105 was prepared from benzofuran-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 789.3 Example                         106:                         Synthesis                        of N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-fluorophenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-( piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide (Compound 106) Compound 106 was prepared from imidazo[1,2-b]pyridazine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 790.4 Example                         107:                         Synthesis                        of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)benzo[d]thiazole-7-carboxamide (Compound 107) Compound 107 was prepared from 7-carboxybenzothiazole as a starting material according to General Synthetic Method A. MS [M+H]+: 814.3 Example                         108:                         Synthesis                        of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxamide (Compound 108) Compound 108 was prepared from 1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 855.4 N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 109) Compound 109 was prepared from 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 829.3 Example                         110:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide (Compound 110) Compound 110 was prepared from 4H-thieno[3,2-b]pyrrole-5-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 802.3 Example                         111:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)quinoline-4-carboxamide (Compound 111) Compound 111 was prepared from quinoline-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 808.4 Example                         112:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)quinoline-5-carboxamide (Compound 112) Compound 112 was prepared from quinoline-5-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 808.4 Example                         113:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-6-carboxamide (Compound 113) Compound 113 was prepared from imidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 797.4 Example                         114:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-7-carboxamide (Compound 114) Compound 114 was prepared from imidazo[1,2-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 797.4 Example                         115:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-6-carboxamide (Compound 115) Compound 115 was prepared from 1H-benzimidazole-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 797.4 Example                         116:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1,5-naphthyridine-3-carboxamide (Compound 116) Compound 116 was prepared from 1,5-naphthyridine-3-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 809.4 Example                         117:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-4-carboxamide (Compound 117) Compound 117 was prepared from 7-azaindole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 797.4 Example                         118:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)isoquinoline-8-carboxamide (Compound 118) Compound 118 was prepared from 8-isoquinoline-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 808.4 Example                         119:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)quinoxaline-5-carboxamide (Compound 119) Compound 119 was prepared from quinoxaline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 809.4 Example                         120:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-5-carboxamide (Compound 120) Compound 120 was prepared from 7-azaindole-5-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 797.4 Example                         121:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 121) Compound 121 was prepared from 2-methylimidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 811.4 Example                         122:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)benzo[c][1,2,5]thiadiazole-4-carboxamide (Compound 122) Compound 122 was prepared from 2,1,3-benzothiadiazole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 815.3 Example                         123:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1H-indole-4-carboxamide (Compound 123) Compound 123 was prepared from indole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 796.4 Example                         124:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1H-indole-5-carboxamide (Compound 124) Compound 124 was prepared from indole-5-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 796.4 Example                         125:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)quinoline-6-carboxamide (Compound 125) Compound 125 was prepared from quinoline-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 808.4 Example                         126:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)benzo[b]thiophene-3-carboxamide (Compound 126) Compound 126 was prepared from 1-benzothiophene-3-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 813.3 Example                         127:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)isoquinoline-5-carboxamide (Compound 127) Compound 127 was prepared from isoquinoline-5-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 808.4 Example                         128:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-6-carboxamide (Compound 128) Compound 128 was prepared from imidazo[1,2-b]pyridazine-6-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 798.4 Example                         129:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)imidazo[1,5-a]pyridine-8-carboxamide (Compound 129) Compound 129 was prepared from imidazole[1,5-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 797.4 Example                         130:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-2-methyl-1H-benzo[d]imidazole-5-carboxamide (Compound 130) Compound 130 was prepared from 2-methyl-1H-benzimidazole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 811.4 Example                         131:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-8-carboxamide (Compound 131) Compound 131 was prepared from imidazo[1,2-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 797.4 Example                         132:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-3-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 132) Compound 132 was prepared from 3-methylimidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 811.4 Example                         133:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-4-carboxamide (Compound 133) Compound 133 was prepared from benzimidazole-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 797.4 Example                         134:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1-(3-methoxyphenyl)-1H-pyrazole-4-carboxamide (Compound 134) Compound 134 was prepared from 1-(3-methoxyphenyl)pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 853.4 Example                         135:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)benzo[c][1,2,5]thiadiazole-5-carboxamide (Compound 135) Compound 135 was prepared from 2,1,3-benzothiadiazole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 815.3 Example                         136:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)thieno[3,2-d]pyrimidine-4-carboxamide (Compound 136) Compound 136 was prepared from thieno[3,2-d]pyrimidine-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 815.3 Example                         137:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)thieno[2,3-c]pyridine-2-carboxamide (Compound 137) Compound 137 was prepared from thiophene[2,3-c]pyridine-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 814.3 Example                         138:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 138) Compound 138 was prepared from 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 829.3 Example                         139:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide (Compound 139) Compound 139 was prepared from [1,2,4]triazolo[4,3-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 798.4 N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (Compound 140) Compound 140 was prepared from [1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 798.4 Example                         141:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 141) Compound 141 was prepared from 1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 891.4 Example                         142:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(pip eridin-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-3-carboxamide (Compound 142) Compound 142 was prepared from 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                         143:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzo[d]thiazole-7-carboxamide (Compound 143) Compound 143 was prepared from 7-carboxybenzothiazole as a starting material according to General Synthetic Method A. MS [M+H]+: 800.3 Example                         144:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-7-carboxamide (Compound 144) Compound 144 was prepared from imidazo[1,2-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 783.4 Example                         145:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1,5-naphthyridine-3-carboxamide (Compound 145) Compound 145 was prepared from 1,5-naphthyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 795.4 Example                         146:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-8-carboxamide (Compound 146) Compound 146 was prepared from imidazo[1,2-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 783.4 Example                         147:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-4-carboxamide (Compound 147) Compound 147 was prepared from benzimidazole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 783.4 Example                         148:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (Compound 148) Compound 148 was prepared from pyrazolo[1,5-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 783.4 Example                         149:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-4-phenoxybenzamide (Compound 149) Compound 149 was prepared from 4-phenoxybenzenecarboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 835.4 Example                         150:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-6-carboxamide (Compound 150) Compound 150 was prepared from imidazo[1,2-b]pyridazine-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 784.4 Example                         151:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide (Compound 151) Compound 151 was prepared from [1,2,4]triazolo[4,3-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 784.4 Example                         152:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (Compound 152) Compound 152 was prepared from [1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 784.4 Example                         153:                         Synthesis                         of 4-amino-N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6 -(piperidin-1-yl)-2H-indazol-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide (Compound 153) Compound 153 was prepared from 4-aminothieno[3,2-d]pyrimidine-7-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 816.3 Example                         154:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-2-carboxamide (Compound 154) Compound 154 was prepared from imidazo[1,2-b]pyridazine-2-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 784.4 Example                         155:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-3H-imidazo[4,5-b]pyridine-7-carboxamide (Compound 155) Compound 155 was prepared from 3H-imidazolo[4,5-b]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 784.4 Example                         156:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide (Compound 156) Compound 156 was prepared from 3H-imidazo[4,5-c]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 784.4 Example                         157:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-(2-methylpyridin-4-yl)thiazole-4-carboxamide (Compound 157) Compound 157 was prepared from 2-(2-methylpyridine-4-yl)thiazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 841.4 Example                         158:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-(pyrimidin-2-yl)oxazole-4-carboxamide (Compound 158) Compound 158 was prepared from 2-(pyrimidine-2-yl)oxazole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 812.4 Example                         159:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)oxazole-4-carboxamide (Compound 159) Compound 159 was prepared from 2-(1-methyl-1H-pyrazole-4-yl)oxazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 814.4 Example                         160:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-phenylthiazole-4-carboxamide (Compound 160) Compound 160 was prepared from 2-phenyl-1,3-thiazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 826.4 Example                         161:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzofuran-7-carboxamide (Compound 161) Compound 161 was prepared from benzofuran-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 783.4 Example                         162:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzofuran-3-carboxamide (Compound 162) Compound 162 was prepared from benzofuran-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 783.4 Example                         163:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-carboxamide (Compound 163) Compound 163 was prepared from pyrazole[1,5-a] 4,5,6,7-tetrahydropyridine-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 787.4 Example                         164:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide (Compound 164) Compound 164 was prepared from 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 773.4 Example                         165:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydro-1H-indazole-3-carboxamide (Compound 165) Compound 165 was prepared from 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 787.4 Example                         166:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 166) Compound 166 was prepared from 2-(4-pyridineyl)thiazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 827.3 Example                         167:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-6-carboxamide (Compound 167) Compound 167 was prepared from imidazo[1,2-b]pyridazine-6-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 784.4 Example                         168:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-8-carboxamide (Compound 168) Compound 168 was prepared from imidazo[1,2-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 783.4 Example                         169:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-4-carboxamide (Compound 169) Compound 169 was prepared from benzimidazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 783.4 Example                         170:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide (Compound 170) Compound 170 was prepared from [1,2,4]triazolo[4,3-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 784.4 N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (Compound 171) Compound 171 was prepared from [1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 784.4 Example                         172:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (Compound 172) Compound 172 was prepared from pyrazolo[1,5-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 783.4 Example                         173:                         Synthesis                         of 4-amino-N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6 -(piperidin-1-yl)-2H-indazol-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide (Compound 173) Compound 173 was prepared from 4-aminothieno[3,2-d]pyrimidine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 816.3 Example                         174:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-2-carboxamide (Compound 174) Compound 174 was prepared from imidazo[1,2-b]pyridazine-2-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 784.4 Example                         175:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-3H-imidazo[4,5-b]pyridine-7-carboxamide (Compound 175) Compound 175 was prepared from 3H-imidazo[4,5-b]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 784.4 Example                         176:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-(2-methylpyridin-4-yl)thiazole-4-carboxamide (Compound 176) Compound 176 was prepared from 2-(2-methylpyridine-4-yl)thiazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 841.4 Example                         177:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-(pyrimidin-2-yl)oxazole-4-carboxamide (Compound 177) Compound 177 was prepared from 2-(pyrimidine-2-yl)oxazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 812.4 Example                         178:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-(1-methyl-1H-pyrazol-4-yl)oxazole-4-carboxamide (Compound 178) Compound 178 was prepared from 2-(1-methyl-1H-pyrazole-4-yl)oxazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 814.4 Example                         179:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-4-phenoxybenzamide (Compound 179) Compound 179 was prepared from 4-phenoxybenzenecarboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 835.4 Example                         180:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-phenylthiazole-4-carboxamide (Compound 180) Compound 180 was prepared from 2-phenyl-1,3-thiazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 826.3 Example                         181:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzofuran-7-carboxamide (Compound 181) Compound 181 was prepared from benzofuran-7-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 783.4 Example                         182:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzofuran-3-carboxamide (Compound 182) Compound 182 was prepared from benzofuran-3-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 783.4 Example                         183:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-carboxamide (Compound 183) Compound 183 was prepared from pyrazole[1,5-a] 4,5,6,7-tetrahydropyridine-2-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 787.4 Example                         184:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydro-1H-indazole-3-carboxamide (Compound 184) Compound 184 was prepared from 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 787.4 Example                         185:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)benzo[d]thiazole-7-carboxamide (Compound 185) Compound 185 was prepared from 7-carboxybenzothiazole as a starting material according to General Synthetic Method A. MS [M+H]+: 818.3 Example                         186:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 186) Compound 186 was prepared from 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 833.4 Example                         187:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide (Compound 187) Compound 187 was prepared from 4H-thieno[3,2-b]pyrrole-5-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 806.3 Example                         188:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)quinoline-4-carboxamide (Compound 188) Compound 188 was prepared from quinoline-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 812.4 Example                         189:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4- yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)quinoline-5-carboxamide (Compound 189) Compound 189 was prepared from quinoline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 812.4 Example                         190:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-6-carboxamide (Compound 190) Compound 190 was prepared from imidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 801.4 Example                         191:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-7-carboxamide (Compound 191) Compound 191 was prepared from imidazo[1,2-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 801.4 Example                         192:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1,5-naphthyridine-3-carboxamide (Compound 192) Compound 192 was prepared from 1,5-naphthyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 813.4 Example                         193:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-4-carboxamide (Compound 193) Compound 193 was prepared from 7-azaindole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                         194:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)benzo[c][1,2,5]thiadiazole-4-carboxamide (Compound 194) Compound 194 was prepared from 2,1,3-benzothiadiazole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 819.3 Example                         195:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1H-indole-4-carboxamide (Compound 195) Compound 195 was prepared from indole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 800.4 Example                         196:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1H-indole-5-carboxamide (Compound 196) Compound 196 was prepared from indole-5-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 800.4 Example                         197:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)quinoline-6-carboxamide (Compound 197) Compound 197 was prepared from quinoline-6-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 812.4 Example                         198:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)benzo[b]thiophene-3-carboxamide (Compound 198) Compound 198 was prepared from 1-benzothiophene-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 817.4 Example                         199:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-methyl-5-phenyl-1H-pyrazole-4-carboxamide (Compound 199) Compound 199 was prepared from 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 841.4 Example                         200:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-6-carboxamide (Compound 200) Compound 200 was prepared from imidazo[1,2-b]pyridazine-6-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 802.4 Example                         201:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,5-a]pyridine-8-carboxamide (Compound 201) Compound 201 was prepared from imidazo[1,5-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 801.4 Example                         202:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-8-carboxamide (Compound 202) Compound 202 was prepared from imidazo[1,2-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 801.4 Example                         203:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)isoquinoline-8-carboxamide (Compound 203) Compound 203 was prepared from 8-isoquinoline-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 812.4 Example                         204:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)quinoxaline-5-carboxamide (Compound 204) Compound 204 was prepared from quinoxaline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 813.4 Example                         205:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-5-carboxamide (Compound 205) Compound 205 was prepared from 7-azaindole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                         206:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 206) Compound 206 was prepared from 2-methyl-6-imidazo[2,1-a]pyridinecarboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 815.4 Example                         207:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)isoquinoline-5-carboxamide (Compound 207) Compound 207 was prepared from isoquinoline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 812.4 (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-3-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 208) Compound 208 was prepared from 3-methylimidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 815.4 Example                       209:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-4-carboxamide (Compound 209) Compound 209 was prepared from benzimidazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                       210:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-(3-methoxyphenyl)-1H-pyrazole-4-carboxamide (Compound 210) Compound 210 was prepared from 1-(3-methoxyphenyl)pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 857.4 Example                         211:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)benzo[c][1,2,5]thiadiazole-5-carboxamide (Compound 211) Compound 211 was prepared from 2,1,3-benzothiadiazole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 819.3 Example                       212:                       Synthesis                       of (S)-4-amino-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)pip eridin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide (Compound 212) Compound 212 was prepared from 4-aminothieno[3,2-d]pyrimidine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 834.3 Example                       213:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide (Compound 213) Compound 213 was prepared from 5-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 841.4 Example                       214:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-2-carboxamide (Compound 214) Compound 214 was prepared from imidazo[1,2-b]pyridazine-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 802.4 Example                       215:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyrazine-3-carboxamide (Compound 215) Compound 215 was prepared from imidazo[1,2-a]pyrazine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 802.4 Example                       216:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1H-pyrrolo[3,2-c]pyridine-7-carboxamide (Compound 216) Compound 216 was prepared from 5-azaindole-7-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 801.4 Example                       217:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-b]pyridazine-3-carboxamide (Compound 217) Compound 217 was prepared from pyrazolo[1,5-b]pyridazine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 802.4 Example                       218:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1H-indole-6-carboxamide (Compound 218) Compound 218 was prepared from 6-indolecarboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 800.42 Example                       219:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-3H-imidazo[4,5-b]pyridine-7-carboxamide (Compound 219) Compound 219 was prepared from 3H-imidazolo[4,5-b]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 802.4 Example                       220:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4- yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-d]pyrimidine-4-carboxamide (Compound 220) Compound 220 was prepared from 7H-pyrrolo[2,3-d]pyrimidine-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 802.4 Example                       221:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide (Compound 221) Compound 221 was prepared from 3H-imidazolo[4,5-c]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 802.4 Example                         222:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-a]pyrimidine-6-carboxamide (Compound 222) Compound 222 was prepared from pyrazolo[1,5-a]pyrimidine-6-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 802.4 Example                         223:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1H-pyrazolo[4,3-c]pyridine-4-carboxamide (Compound 223) Compound 223 was prepared from 1H-pyrazolo[4,3-c]pyridine-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 802.4 Example                         224:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-2-(pyridin-4-yl)thiazole-4-carboxamide (Compound 224) Compound 224 was prepared from 2-(pyridin-4-yl)thiazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 845.3 Example                         225:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)benzofuran-4-carboxamide (Compound 225) Compound 225 was prepared from benzofuran-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                         226:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,2-b]pyridazine-3-carboxamide (Compound 226) Compound 226 was prepared from imidazo[1,2-b]pyridazine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 802.4 Example                       227:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxamide (Compound 227) Compound 227 was prepared from 1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 841.4 Example                       228:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 228) Compound 228 was prepared from 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 815.4 Example                       229:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-4H-thieno[3,2-b]pyrrole-5-carboxamide (Compound 229) Compound 229 was prepared from 4H-thieno[3,2-b]pyrrole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 788.3 Example                       230:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)quinoline-4-carboxamide (Compound 230) Compound 230 was prepared from quinoline-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 794.4 Example                       231:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)quinoline-5-carboxamide (Compound 231) Compound 231 was prepared from quinoline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 794.4 Example                       232:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,2-a]pyridine-6-carboxamide (Compound 232) Compound 232 was prepared from imidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 783.4 Example                         233:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-6-carboxamide (Compound 233) Compound 233 was prepared from 1H-benzimidazole-6-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 783.4 Example                         234:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-4-carboxamide (Compound 234) Compound 234 was prepared from 7-azaindole-4-carboxylic acid as a starting material according to General Synthetic Method B. MS [M+H]+: 783.4 Example                         235:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)isoquinoline-8-carboxamide (Compound 235) Compound 235 was prepared from 8-isoquinoline-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 794.4 Example                         236:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)quinoxaline-5-carboxamide (Compound 236) Compound 236 was prepared from quinoxaline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 795.4 Example                         237:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-7H-pyrrolo[2,3-b]pyridine-5-carboxamide (Compound 237) Compound 237 was prepared from 7-azaindole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 783.4 Example                         238:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 238) Compound 238 was prepared from 2-methyl-6-imidazo[2,1-a]pyridinecarboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 797.4 N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzo[c][1,2,5]thiadiazole-4-carboxamide (Compound 239) Compound 239 was prepared from 2,1,3-benzothiadiazole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 801.3 Example                         240:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1H-indole-4-carboxamide (Compound 240) Compound 240 was prepared from indole-4-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 782.4 Example                         241:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1H-indole-5-carboxamide (Compound 241) Compound 241 was prepared from indole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 782.4 Example                         242:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)quinoline-6-carboxamide (Compound 242) Compound 242 was prepared from quinoline-6-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 794.4 Example                         243:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)benzo[b]thiophene-3-carboxamide (Compound 243) Compound 243 was prepared from 1-benzothiophene-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 799.3 Example                         244:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)isoquinoline-5-carboxamide (Compound 244) Compound 244 was prepared from isoquinoline-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 794.4 Example                         245:                         Synthesis                         of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)imidazo[1,5-a]pyridine-8-carboxamide (Compound 245) Compound 245 was prepared from imidazole[1,5-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 783.4 Example                       246:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1H-benzo[d]imidazole-6-carboxamide (Compound 246) Compound 246 was prepared from 1H-benzimidazole-6-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 801.4 Example                       247:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-2-methyl-1H-benzo[d]imidazole-5-carboxamide (Compound 247) Compound 247 was prepared from 2-methyl-1H-benzimidazole-5-carboxylic acid as a starting material according to General Synthetic Method D. MS [M+H]+: 815.4 Example                       248:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)thieno[3,2-d]pyrimidine-4-carboxamide (Compound 248) Compound 248 was prepared from thieno[3,2-d]pyrimidine-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 819.3 Example                       249:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)thieno[2,3-c]pyridine-2-carboxamide (Compound 249) Compound 249 was prepared from thiophene[2,3-c]pyridine-2-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 818.3 Example                       250:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 250) Compound 250 was prepared from 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 833.4 Example                       251:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide (Compound 251) Compound 251 was prepared from [1,2,4]triazolo[4,3-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 802.4 Example                       252:                       Synthesis                       of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridine-7-carboxamide (Compound 252) Compound 252 was prepared from [1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 802.4 Example                         253:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide (Compound 253) Compound 253 was prepared from 1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 895.4 Example                         254:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-3-carboxamide (Compound 254) Compound 254 was prepared from 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 805.4 Example                         255:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (Compound 255) Compound 255 was prepared from pyrazolo[1,5-a]pyridine-3-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 801.4 Example                         256:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)-1H-indole-7-carboxamide (Compound 256) Compound 256 was prepared from 7-indolecarboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 800.4 Example                        257:                         Synthesis                         of (S)-N-(2-(1-((1-(4-((2,6-dioxopiperidin-3-yl)carbamoyl)-3-methoxyphenyl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperidin-1-yl)-2H-indazol-5-yl)imidazo[1,5-a]pyridine-8-carboxamide (Compound 257) Compound 257 was prepared from imidazole[1,5-a]pyridine-8-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 801.4 Example                       258:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-2-methyl-1H-benzo[d]imidazole-5-carboxamide (Compound 258) Compound 258 was prepared from 2-methyl-1H-benzimidazole-5-carboxylic acid as a starting material according to General Synthetic Method A. MS [M+H]+: 797.4 Example                       259:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-3-methylimidazo[1,2-a]pyridine-6-carboxamide (Compound 259) Compound 259 was prepared from 3-methylimidazo[1,2-a]pyridine-6-carboxylic acid as a starting material according to General Synthetic Method C. MS [M+H]+: 797.4 Example                       260:                       Synthesis                       of N-(2-(1-((1-(2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-5-yl)piperidin-4-yl)methyl)piperidin-4-yl)-6-(piperid in-1-yl)-2H-indazol-5-yl)-1-(3-methoxyphenyl)-1H-pyrazole-4-carboxamide (Compound 260) Compound 260 was prepared from 1-(3-methoxyphenyl)pyrazole-4-carboxylic acid as a starting material according to General Syn...

Claims

1. A compound of Formula (IA), a stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptablesalt, or prodrug thereof:E3(IA)wherein,Ring B iswherein “' /  ” is a single bond or a double bond;W1, W2, W3, W4 are each independently C=O, CH, CH2, O, N, CR1, or NR1;W5, W6, W7 are each independently N or CH;R1 is hydrogen, halogen, C1-6 alkyl, or C1-6 haloalkyl;Rx is hydrogen, C1-6 alkoxy, -C(O)NRx1Rx2, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkoxy is optionally substituted with one or more C3-6 cycloalkyl groups; said 4- to 8-membered nitrogen-containing heterocycloalkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more substituents selected from halogen, hydroxyl, C1-6 alkyl, or hydroxy-substituted C1-6 alkyl; said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or Sas ring atoms;Rx1, Rx2 are each independently hydrogen or C1-6 alkyl;Lx is -C(O)NH- or -CH2-NH-;Ring A is:(i) an 8- to 10-membered bicyclic heteroaryl; said 8- to 10-membered bicyclic heteroaryl is formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring;(ii) an 8- to 10-membered bicyclic heteroaryl; said 8- to 10-membered bicyclic heteroaryl is formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring;(iii) a 9- or 10-membered bicyclic heteroaryl; said 9- or 10-membered bicyclic heteroaryl is formed by fusion of a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring;(iv) a 5- or 6-membered monocyclic heteroaryl; or,(v) C6-8 aryl;or,(Sg] '''S<x    '^S2x : : :' 'q2Ring A is:          °6           °4         ;wherein S1, S2, S3, S4, S5, S6, S7, S8 are each independently selected from CH2, CH, NH, N, O, or S;S9, S10 are each independently selected from N or CH; q1, q2 are each independently 0, 1, or 2;Ry is hydrogen, halogen, hydroxyl, =O, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C3-6 cycloalkyl, -O-Ra-, -NRbRc, a 4- to 8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, wherein said C1-6 alkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more R1 substituents;R1 is halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, -OC(O)-C1-6 alkyl, -OP(O)(OH)2, or a 4- to 12-membered heterocycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-6 cycloalkyl, or 4- to 12-membered heterocycloalkyl is optionally substituted with one or more substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl, or C1-6 alkoxy;Ra is C1-6 alkyl or C6-8 aryl;Rb, Rc are each independently hydrogen or C1-3 alkyl;y is 0, 1, 2, 3, or 4;L is; wherein the position indicated by “    ”is thepoint of attachment to E3, and the position indicated by “is the point of attachment to Ring B;Q1, Q2, Q3 are each independently a 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10cycloalkyl, wherein said 4- to 12-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom; said 4- to 12-membered nitrogen-containing heterocycloalkyl or C3-10 cycloalkyl is optionally substituted with one or more substituents selected from halogen and hydroxyl;L1, L2, L3, L4 are each independently -CRL1RL2-, -NRL3-, -CRL1RL2-NRL3-, -NRL3-CRL1RL2-, or -ORL4;RL1, RL2, RL3, RL4 are each independently hydrogen, halogen, =O, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkynyl;m1, m2, m3, m4, m5, m6, m7 are each independently 0 or 1;E3 is an E3 ubiquitin ligase binding moiety.

2. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to claim 1, wherein the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A is a structure represented by Formula (A1) or Formula (A2):(A1)(A2)wherein U1 is N or CRU1; U2 is N or CRU2; U3 is N or CRU3; U4 is N or CRU4; U5 is N or CRU5; U6 is N or CRU6; U7 is N or CRU7; U8 is N or CRU8; and at least one of U1, U2, U3, U4, U5, U6, U7, U8 is N; RU1, RU2, RU3, RU4, RU5, RU6, RU7, RU8 are each independently hydrogen or Ry.

3. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to claim 1, wherein the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A is a structure represented by Formula (A3) or Formula (A4):(A3)(A4);wherein Z1 is N or CRZ1; Z2 is NRZ2, O, or S; Z3 is N or CRZ3; Z4 is N or CRZ4; Z5 is N or CRZ5; Z6 is N orCRZ6; and at least one of Z3, Z4, Z5, Z6 is N; RZ0, RZ1, RZ2, RZ3, RZ4, RZ5, RZ6 are each independently hydrogen orRy.

4. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to claim 1, wherein the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A is astructure represented by Formula (A5):(A5);wherein P1 is NRP1, O, or S; P2 is NRP2, O, or S; P3 is N or CRP3; P4 is N or CRP4; and at least one of P3, P4 isN;RP1, RP2, RP3, RP4 are each independently hydrogen or Ry.

5. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to claim 1, wherein the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A is astructure represented by Formula (A6):(A6);wherein V1 is N or CRV1; V2 is N or CRV2; V3 is N or CRV3; V4 is N or CRV4; V5 is N or CRV5; V6 is N orCRV6; V7 is N or CRV7; V8 is N or CRV8; V9 is N or CRV9; and at least one of V1, V2, V3, V4, V5, V6, V7, V8, V9 isN; RV1, RV2, RV3, RV4, RV5, RV6, RV7, RV8, RV9 are each independently hydrogen or Ry.

6. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to claim 1, wherein the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring in Ring A is a structure represented by Formula (A7), Formula (A8), Formula (A9), Formula (A10), or Formula (A11):(A7);(A8);(A10);(A11);wherein H1 is N or CRH1; H2 is N or CRH2; H3 is N or CRH3; H4 is NRH4a, O, S, or CRH4bRH4c; H5 is NRH5a, O,S, or CRH5bRH5c; H6 is NRH6a, O, S, or CRH6bRH6c; H7 is NRH7a, O, S, or CRH7bRH7c; RH0, RH1, RH2, RH3, RH4a, RH4b,RH4c, RH5a, RH5b, RH5c, RH6a, RH6b, RH6c, RH7a, RH7b, RH7c are each independently hydrogen or Ry;G1 is N, O, S, or CRG1; G2 is NRG2a, O, S, or CRG2bRG2c; G3 is NRG3a, O, S, or CRG3bRG3c; G4 is NRG4a, O, S,or CRG4bRG4c; G5 is NRG5a, O, S, or CRG5bRG5c; G6 is NRG6a, O, S, or CRG6bRG6c; RG0, RG1, RG2a, RG2b, RG2c, RG3a,RG3b, RG3c, RG4a, RG4b, RG4c, RG5a, RG5b, RG5c, RG6a, RG6b, RG6c are each independently hydrogen or Ry;and the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroarylring with a 5- or 6-membered monocyclic heterocycloalkyl ring is a structure represented by Formula (A12) orFormula (A13):(A12);(A13);wherein M1 is N or CRM1; M2 is N or CRM2; M3 is N or CRM3; M4 is NRM4; M5 is NRM5a, O, S, or CRM5bRM5c;M6 is NRM6a, O, S, or CRM6bRM6c; M7 is NRM7a, O, S, or CRM7bRM7c; M8 is NRM8a, O, S, or CRM8bRM8c; RM1, RM2,RM3, RM4, RM5a, RM5b, RM5c, RM6a, RM6b, RM6c, RM7a, RM7b, RM7c, RM8a, RM8b, RM8c are each independently hydrogenor Ry; p1, p2 are each independently 0, 1, or 2.

7. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to claim 1, wherein in the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A, the two 5-or 6-membered monocyclic heteroaryl rings are each independently selected from the group consisting of:said groups being optionally substituted with one or more Ry substituents; “    ”represents the carbon atom or heteroatom to which the ring is attached, which is an adjacent atom pair of the carbonatom or heteroatom shared by an other ring when the ring is fused to the other ring;preferably, in the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclicheteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring in Ring A, the 5- or 6-memberedmonocyclic heteroaryl ring is selected from the group consisting of:,           ,           ,        j\ , said groups being optionally substituted with one or more Rysubstituents; “    ” represents the carbon atom or heteroatom to which the ring is attached, which is an adjacentatom pair of the carbon atom or heteroatom shared by an other ring when the ring is fused to the other ring;preferably, in the 8- to 10-membered bicyclic heteroaryl formed by fusion of a 5- or 6-membered monocyclicheteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring in Ring A, the 5- or 6-memberedmonocyclic heterocycloalkyl ring is selected from the group consisting of:,,,,H                                     H, said groups being optionally substituted with one or more Ry substituents; “    ” represents thecarbon atom or heteroatom to which the ring is attached, which is an adjacent atom pair of the carbon atom or heteroatom shared by an other ring when the ring is fused to the other ring;preferably, in the 9- or 10-membered bicyclic heteroaryl formed by fusion of a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring in Ring A, the 5- or 6-membered monocyclic heteroaryl ring is selected from the group consisting of:, wherein RD is hydrogen or Ry;” represents two carbon atoms to which the ring isattached, which is an adjacent atom pair of the carbon atoms shared by an other ring when the ring is fused to theother ring;preferably, when Ring A is a 5- or 6-membered monocyclic heteroaryl, the 5- or 6-membered monocyclicheteroaryl is selected from the group consisting of: / = N / = NN. / ) N- / / NN / / H N, J N,       n / L, N-VN , N , N        ,           ,           i Said groups being optionally substituted with one ormore Rysubstituents; the positionindicated by “     ” represents the point of attachment to Lx;preferably, when Ring A is C6-8 aryl, the C6-8 aryl is selected from phenyl or naphthyl, said groups beingoptionally substituted with one or more Ry substituents.

8. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to any one of claims 1 to 7, wherein Ring B ispreferably, Ring B is9. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to any one of claims 1 to 8, wherein the compound of Formula (IA) has a structure represented bythe following Formula (I):wherein Ring A, E3, L, W1, W2, W3, W4, Rx, Lx, Ry, and y are each defined as above;preferably, the compound of Formula (I) has a structure represented by the following Formula (I-1):(I-1),wherein Ring A, E3, L, Rx, Lx, Ry, and y are each defined as above.

10. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 9, wherein Ry is selected from: halogen, =O, hydroxyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, -NH2, -NHCH3, -N(CH3)2, -CH2-OC(O)(CH3)3, -CH2-OP(O)(OH)2, fluoromethyl, difluoromethyl, trifluoromethyl,fluoroethyl, difluoroethyl, trifluoroethyl, thienyl, N-alkylpyrrolidinonyl, furyl, morpholinyl, piperazinyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl, triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, phenyl, naphthyl, -O-thienyl,-O-N-alkylpyrrolidinonyl, -O-furyl, -O-thiazolyl, -O-isothiazolyl, -O-imidazolyl, -O-oxazolyl, -O-pyrrolyl,-O-pyrazolyl, -O-triazolyl, -O-1,2,3-triazolyl, -O-1,2,4-triazolyl, -O-1,2,5-triazolyl, -O-1,3,4-triazolyl, -O-tetrazolyl,-O-isoxazolyl,     -O-oxadiazolyl,     -O-1,2,3-oxadiazolyl,     -O-1,2,4-oxadiazolyl,     -O-1,2,5-oxadiazolyl,-O-1,3,4-oxadiazolyl, -O-thiadiazolyl, -O-pyridyl, -O-pyridazinyl, -O-pyrimidinyl, -O-pyrazinyl, -O-phenyl;wherein said thienyl, N-alkylpyrrolidinonyl, furyl, thiazolyl, isothiazolyl, imidazolyl, oxazolyl, pyrrolyl, pyrazolyl,triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, isoxazolyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiadiazolyl, pyridyl, pyridazinyl,pyrimidinyl, pyrazinyl, phenyl, and naphthyl are optionally substituted with one or more substituents selected fromF, Cl, Br, I, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, fluoromethyl, difluoromethyl, or trifluoromethyl;preferably, Ry is selected from: halogen, hydroxyl, =O, amino, methylamino, dimethylamino, methyl,tert-butyl, trifluoromethyl, methoxy, -CH2-OC(O)(CH3)3, -CH2-OP(O)(OH)2, morpholinyl,11. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to any one of claims 1 to 10, wherein Ring A is selected from the following groups:optionally substituted with one or more Ry substituents;; said groups beingpreferably, Ring A is selected from:543Inh212. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 10, wherein Rx is hydrogen, C1-6 alkoxy, -C(O)NRx1Rx2, a 4- to8-membered nitrogen-containing heterocycloalkyl, a 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl, whereinsaid C1-6 alkoxy is optionally substituted with one or more C3-6 cycloalkyl groups; said 4- to 8-memberednitrogen-containing heterocycloalkyl, 5- or 6-membered monocyclic heteroaryl, or C6-8 aryl is optionally substituted with one or more substituents selected from halogen, hydroxyl, C1-6 alkyl, hydroxy-substituted C1-6 alkyl, or halogen-substituted C1-6 alkyl; said 4- to 8-membered nitrogen-containing heterocycloalkyl contains at least one N atom as a ring atom and contains 0 to 3 heteroatoms independently selected from N, O, or S as ringatoms;Rx1, Rx2 are each independently hydrogen or methyl, ethyl, or propyl;preferably, Rx is methoxy, ethoxy, -C(O)N(CH3)2, -C(O)NH2,or, wherein said methoxy or ethoxy is optionally substituted with one or morecyclopropyl groups,and saidoroptionally substituted with one or more substituents selected from hydroxyl, F, Cl, Br, methyl, ethyl, propyl,isopropyl, hydroxymethyl, hydroxyethyl, or hydroxypropyl;preferably, Rx is methoxy, -C(O)NH2,13. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 12, wherein Lx is selected from *-C(O)NH-**, *-CH2-NH-**, or *-NH-C(O)-**; preferably, Lx is selected from *-C(O)NH-** or *-CH2-NH-**; wherein the position indicated by “*” represents the point of attachment to Ring A, and the position indicated by “**” represents the point of attachment to the group on the other side of Lx.

14. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 13, wherein the compound is a compound represented by Formula (IA1) or Formula (IA2):RX                                  (IA1),RX                                     (IA2),wherein E3, L, W1, W2, W3, W4, Rx, Lx, and Ring A are each defined as above;F1 is NRF1, O, or S; F2 is N or CRF2; F3 is N or CRF3; F4 is N or CRF4; and at least one of F1, F2, F3, F4 is N;RF1, RF2, RF3, RF4 are each independently hydrogen or R1;K1 is NRK1 or CRK2; K2 is N or CRK2; K3 is N or CRK3; K4 is N or CRK4; K5 is N or CRK5; and at least one ofK1, K2, K3, K4, K5 is N; RK1, RK2, RK3, RK4, RK5 are each independently hydrogen or R1;preferably, the compound is a compound represented by Formula (IA1-1) or Formula (IA2-1):(IA1-1),(IA2-1),wherein E3, L, Rx, Lx, and Ring A are each defined as above;F1 is NRF1, O, or S; F2 is N or CRF2; F3 is N or CRF3; F4 is N or CRF4; and at least one of F1, F2, F3, F4 is N;RF1, RF2, RF3, RF4 are each independently hydrogen or R1;K1 is NRK1 or CRK2; K2 is N or CRK2; K3 is N or CRK3; K4 is N or CRK4; K5 is N or CRK5; and at least one ofK1, K2, K3, K4, K5 is N; RK1, RK2, RK3, RK4, RK5 are each independently hydrogen or R1.

15. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to claim 1, wherein the compound is a compound represented by Formula (IB1), Formula (IB2),Formula (IB3), Formula (IB4), or Formula (IB5):E3----L(IB1),Rx                          (IB2),Rx                          (IB3),Rx                          (IB4),Rx                         (IB5),wherein E3, L, W1, W2, W3, W4, Rx, Lx, Ry, and y are each defined as above;preferably, the compound is a compound represented by Formula (IB1-1), Formula (IB2-1), Formula (IB3-1),Formula (IB4-1), or Formula (IB5-1):E3----L(IB1-1),E3E3E3E3----L(IB2-1),(IB3-1),(IB4-1),LxRx(IB5-1),wherein E3, L, Rx, Lx, Ry, and y are each defined as above.

16. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to claim 1, wherein the 4- to 12-membered nitrogen-containing heterocycloalkyl is selected from:X1, X2, X3, X4 are each independently N or -CRd;X5 is a single bond, -O-, -S-, -NRa-, or -NReRf;n1, n2, n3, n4, n5, n6 are each independently 0, 1, 2, or 3;wherein Rd, Re, Rf are each independently hydrogen, hydroxyl, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, or C3-6 cycloalkyl.

17. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to any one of claims 1 to 16, wherein L is selected from:wherein,X1, X2, X3, X4, X11, X12, X21, X22, X31, X32, X41, and X42 are each independently N or -CRd;wherein Rd is hydrogen, hydroxyl, halogen, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, or C3-6 cycloalkyl;n1, n2, n3, n4, n11, n12, n21, n22, n31, n32 are each independently 0, 1, 2, or 3;L1, L2, L3, L4 are each independently -CRL1RL2-, -NRL3-, -CRL1RL2-NRL3-, -NRL3-CRL1RL2-, or -ORL4;RL1, RL2, RL3, RL4 are each independently =O, hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, or C2-6 alkynyl;m1, m2, m3, m4 are each independently 0 or 1;wherein the position indicated by “    ” represents the point of attachment to E3, and the position indicatedby” represents the point of attachment to Ring B.

18. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to any one of claims 1 to 17, wherein L is selected from:wherein the position indicated by “    ” represents the point of attachment to E3, and the position indicatedby “      ” represents the point of attachment to Ring B.

19. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according to any one of claims 1 to 18, wherein E3 has a structure represented by Formula (C1), (C2), (C3),(C4), (C5), (C6), (C7), (C8), or (C9):(C1),(C3),(C4),(C5),(C6),(C7),(C8),(C9)wherein T1, T2, T3, T4, T5 are each independently CH, C, or N;T is CH2, CH(C1-6 alkyl), C=O, SO2, NH, or N(C1-6 alkyl);R2, R5, R6, R8, R9 are each independently hydrogen, C1-6 alkyl, or C1-6 alkoxy, wherein said C1-6 alkyl is optionally substituted with one or more C1-6 alkoxy or -OC(O)-C1-6 alkyl;R3 is hydrogen, hydroxyl, or C1-6 alkyl;R4, R7, R10 are each independently hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, or halo-C1-6 alkyl;m7, m8, m9, m10 are each independently 0, 1, 2, or 3.

20. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrugthereof according toclaim 1, wherein; R7 is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, or halo-C1-6 alkyl;R5 is hydrogen, C1-6 alkyl, or C1-6 alkoxy, wherein said C1-6 alkyl is optionally substituted with one or moresubstituents selected from C1-6 alkoxy or -OC(O)-C1-6 alkyl; m9 is 1, 2, or 3;preferably, R7 is hydrogen, F, Cl, Br, methyl, methoxy, or trifluoromethyl;preferably, R5 is hydrogen or -CH2-OC(O)(CH3)3;preferably, E3y> wpreferably,ooVHN / SI0 n-A H ?y 0 HN—E3 is0.° r\ 0<^N Z.N-N- S a y,                                                     ,o n H I “ttiCTo HWNHO^XHC °N^XH ,,n HVT° NHJf3c^>n Hi (s>rf3cN-NII >,,;hnV o.W o NH °= / F~w ,Ov H y-N\^° xJSlI / ? 'N--XH )H^’NH fo HV^oNHO^U,O. HXSx / ?N-X H jOMe,-oNHML-O,H-Ny.oNHd,o H y^oNH F oAU JI NH \                    ff \ ,P0=O       0 i~XQ Uy,                                                                  ,,,,21. The compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to claim 1, wherein said compound is selected from Table A, Table B, Table C, Table D, or Table E.

22. The compound of Formula (I), stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 21, wherein the compound is capable of degrading BTK protein and / or IRAK4 protein, preferably, the compound is capable of simultaneously degrading BTK and IRAK4 proteins.

23. A pharmaceutical composition, wherein the composition comprises the compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 21.

24. Use of the compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 21, or the pharmaceutical composition according to claim 23, in the preparation of a medicament for treating a disorder mediated by BTK protein and / or IRAK4 protein in a patient;preferably, the disorder mediated by BTK protein and / or IRAK4 protein is selected from: cancer, neurodegenerative disease, viral disease, autoimmune disease, inflammatory disorder, genetic disorder, hormone-related disease, metabolic disorder, condition associated with organ transplantation, immunodeficiency disorder, destructive bone lesion, proliferative disorder, infectious disease, condition associated with cell death, thrombin-induced platelet aggregation, liver disease, pathological immune condition mediated by T cell activation, cardiovascular disorder, and CNS disorder.

25. Use of the compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 21, or the pharmaceutical composition according to claim 20, in the preparation of a BTK and / or IRAK4 degrader; preferably, said degrader is a bifunctional BTK and IRAK4 degrader.

26. A method for simultaneously degrading BTK and / or IRAK4 proteins in a biological sample, comprising contacting the biological sample with the compound, stereoisomer, N-oxide, deuterated derivative, pharmaceutically acceptable salt, or prodrug thereof according to any one of claims 1 to 21, or the pharmaceutical composition according to claim 20.

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