Adhesive decomposing agent and method of use thereof

Abstract

Described herein are adhesion degrader compounds, their various targets, their preparation, pharmaceutical compositions containing them, and their use in the treatment or prevention of conditions, diseases, and disorders mediated by various target proteins.

Description

[Technical Field]

[0001] Related applications This application claims the benefits and priority thereto of U.S. Provisional Patent Application No. 62 / 901,229, filed on 16 September 2019, the entire contents of which are incorporated herein by reference.

[0002] This specification describes adhesion-degrading compounds, their various targets, their preparations, pharmaceutical compositions containing them, and their use in the treatment of conditions, diseases, and disorders mediated by various target proteins. [Background technology]

[0003] The ubiquitin-proteasome pathway (UPP) is a critical pathway that regulates major regulatory proteins and degrades misfolded or abnormal proteins. The UPP is central to multiple cellular processes, and defects or imbalances in it can lead to the pathogenesis of various diseases. The covalent binding of ubiquitin to specific protein substrates is achieved through the action of E3 ubiquitin ligases. These ligases comprise over 500 different proteins and are classified into several classes defined by their structural elements of E3 functional activity.

[0004] Cereblon (CRBN) interacts with damaged DNA-binding protein 1 to form a complex with karin 4 and E3 ubiquitin ligase, which functions as a substrate receptor where proteins recognized by CRBN are ubiquitinated and can be degraded by the proteasome.

[0005] Proteasome-mediated degradation of unwanted or damaged proteins plays a crucial role in maintaining normal cellular functions, including cell survival, proliferation, and growth. Novel roles of CRBNs have been identified, namely, the binding of immunomodulatory drugs (IMiDs), such as thalidomide, to CRBNs, which is now linked to the teratogenic and cytotoxic effects of IMiDs, including lenalidomide, which are widely used in the treatment of multiple myeloma patients. CRBNs may play a vital role in the binding, ubiquitination, and degradation of factors involved in maintaining the function of myeloma cells. [Overview of the project] [Problems that the invention aims to solve]

[0006] Adhesion-degrading compounds that bind to and alter the specificity of cereblon complexes have been shown to induce proteasome-mediated degradation of selected proteins. These molecules can be used to modulate protein expression and may be useful as biochemicals or therapeutic agents for the treatment of diseases or disorders. Adhesion-degrading compounds are needed to target proteins for degradation. This application addresses the need for adhesion-degrading molecules directed at various protein targets. [Means for solving the problem]

[0007] A first aspect of this disclosure relates to compounds that bind to the cereblon complex and alter its specificity to induce ubiquitination and degradation of complex-related proteins, or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof.

[0008] In another embodiment, the present disclosure relates to a compound comprising (i) a tris-tryptophan pocket binding moiety that binds to the tris-tryptophan pocket of cereblon E3 ligase; and (ii) a target affinity moiety covalently bonded to the tris-tryptophan pocket binding moiety that interacts with and alters the surface of cereblon E3 ligase and causes the ligase to have affinity for a target protein.

[0009] Another aspect of the present disclosure is formula (I)

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0010] In another aspect, this disclosure relates to formula (I) [ka] (In the formula, [ka] It is either a single bond or a double bond; R d1 H, -CH2OC(O)R 15 -CH2OP(O)OHOR 15 or -CH2OP(O)(R 15 )2; R d2 H, C 1~6 Alkyl, halogen, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl; R d3 teeth, [ka] [ka] [ka] and; A 1 This is a 5- or 6-membered heterocycline or N,NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 3 R 1d It is a 5-membered heteroaryl substituted with; A 2 C 5~7 Carbocyclyl or N, NR 1k , a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O and S, and carbocykrill and heterocyclyl contain 1-3 R 1d It has been replaced with; X 1 , NR 4 or S; X 2 and X 2a Each of them operates independently, CR 1a or N; Each X 3 CR is independent. 1d or N, and two or fewer X 3 is N; Each X 3’ CR is independent. 1d , CR 1c or N, and two or fewer X 3 is N and at least one X 3’ CR 1c and; Each X 4 CR is independent. 1d or N, and at least one X 4 is N, and there are two or fewer X 4 is N; Each X 5 CR is independent. 1a or N, and two or fewer X 5 is N; X 6 , NR 1k , O or S; X 7 , NR 4 , O or S; R 1a and R 1b These are H and C, respectively, independently. 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl; R 1c C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1c’ C 1~6 Alkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, F, Cl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10(CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; Each R 1d H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2)0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 - Selected from 5- or 6-membered heteroaryls, the alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 It is a haloalkoxy, -CN, F, or Cl; R 1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 It is a haloalkoxy, -CN, F, or Cl; R 1g C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10(CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1g’ C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 2~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2)0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3C(O)O(CH2) 0~4 -5- to 7-member heterocyclyl, -NR 3 C(O)O(CH2) 0~4 -C 6~10 aryl or -NR containing 1 to 3 heteroatoms selected from O, N and S 3 C(O)O(CH2) 0~4 -5- or 6-member heteroaryl, and alkynyl is optionally substituted with 1 to 3 R 2 heterocyclyl is substituted with 1 to 5 R 5 and carbocyclyl, aryl and heteroaryl are optionally substituted with 1 to 5 R 5 ; R 1h is C 4~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 2~6 haloalkyl, C 1~6 alkoxy, C 1~3 haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 )、-(CH2) 0~4 -C(O)N(R 13 )2、-(CH2) 0~6 -C 3~7 carbocyclyl, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~6 -5- to 7-member heterocyclyl, -C 6~10 aryl, -(CH2) 2~6 C 6~10 aryl, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~6 -5- or 6-member heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 carbocyclyl, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~4 NR 3 (CH2) 0~4-5 to 7-member heterocyclyl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 -(CH2) containing 1 to 3 heteroatoms selected from aryl, O, N, and S 0~4 NR 3 (CH2) 0~4 -5- or 6-member heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 -(CH2) containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 0~4 -NR 3 C(O)-5 to 7-member heterocyclyl, -(CH2) 0~4 -NR 3 C(O)-C 6~10 -(CH2) containing 1 to 3 heteroatoms selected from aryl, O, N, and S 0~4 -NR 3 C(O)-5- or 6-member heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5 to 7-member heterocyclyl, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing 1 to 3 heteroatoms selected from aryl or O, N, and S 3 C(O)O(CH2) 0~4 -5- or 6-member heteroaryl, and alkynyl is optionally substituted with 1 to 3 R 2 and carbocyclyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with 1 to 5 R 5 ; R 1h’ is C 4~6 alkyl, C 2~6 alkenyl, C 2~6 alkynyl, C 2~6 haloalkyl, C 1~6 alkoxy, C 1~3Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 )、-(CH2) 0~4 -C(O)N(R 13 )2、-(CH2) 0~6 -C 3~7 carbocyclic, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~6 -5 to 7-membered heterocyclic, -C 6~10 aryl, -(CH2) 2~6 C 6~10 aryl, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 carbocyclic, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~4 NR 3 (CH2) 0~4 -5 to 7-membered heterocyclic, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 aryl, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 -NR 3~7 carbocyclic, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~4 -NR 3 -NR 0~4 C(O)-5 to 7-membered heterocyclic, -(CH2) 3 -NR 6~10 aryl, -(CH2) containing 1 to 3 heteroatoms selected from O, N and S 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted, and heterocyclyls have 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1i H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1j H, C 1~6 Alkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10(CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R on the benzoxazole ring 1d , R 1i and R 1j It is not possible for all of them to be H at the same time; Each R 1k H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -C(O)O(CH2) 0~4 -C 3~7 -C(O)O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~4 -5-7 member heterocycline, -C(O)O(CH2) 0~4 -C 6~10 -C(O)O(CH2) containing aryl or 1 to 3 heteroatoms selected from O, N, and S 0~4 - Selected from 5- or 6-membered heteroaryls, the alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; Each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 and; R 3 is H or C 1~6 It is alkyl; R 4 is H or C 1~6 It is alkyl; Each R 5 Independently, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkyl, halogen, -OH, -C(O)H, -C(O)(C 1~6Alkyl), -C(O)(C 6~10 aryl), -C(O)(5 or 6-membered heteroaryl), -C(O)(C 3~7 Carbocyclyl), -C(O)(5-7 member heterocyclyl), -(CH2) 0~3 C(O)OC 1~6 Alkyl, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-NHC(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -NHS(O)2R 9 , -NR 9 S(O)2R 9 , -S(O) q NHR 9 , -S(O) q N(R 9 )2, -S(O) q R 9 , C 1~6 Hydroxyalkyl, -O(CH2) 1~3 CN, CN, -O(CH2) 0~6 -C 3~7 -O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~6 -5-7 member heterocycline, -O(CH2) 0~3 (C6~C 10 -O(CH2) containing 1 to 3 heteroatoms selected from aryl, adamantyl, O, N, and S 0~3 -5 or 6-membered heteroaryl, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 -C 6~10 -(CH2) containing an aryl group and 1 to 3 heteroatoms selected from O, N, and S. 0~6-5 or 6-membered heteroaryl, alkyl is 1-3 R 6 It is optionally substituted, and carbocyclyl, heterocyclyl, aryl and heteroaryl have 1 to 4 R 8 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7 It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S; or 2 R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7 Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is either optionally replaced by; or two R 5 If they are on the same atom, they form (O); R 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 7 It is optionally replaced by; Each R 7 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, or C 6~10 It is an allele; Each R8 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy, halogen, or -OH; R 9 C 1~6 Alkyl, C 1~6 Haloalkyl, 5-7 membered heterocycline containing 1-3 heteroatoms selected from O, N, and S, C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 11 It is optionally replaced by; Each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or Two R's 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S; Each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 It is alkyl or halogen; or Two R's 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by; Each R12 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy or C 1~3 It is a haloalkoxy; R 13 Each of these occurrences is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 6~10 A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the alkyl has 1 to 2 C 1~6 They are optionally substituted with alkoxys, and aryls and heteroaryls have 1 to 3 R 14 It is optionally replaced by; Each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, C 6~10 A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S; R 15 is H or C 1~6 It is alkyl; and (q is 0, 1, or 2) This relates to compounds or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers.

[0011] In one aspect of this disclosure, hydrogen in the compound of formula (I) is present in its normal isotopic abundance. In a preferred aspect of this disclosure, hydrogen is isotopically enriched with deuterium (D), and in a particularly preferred aspect of the present invention, at position R, as will be discussed in more detail below with respect to isotopes and isotopic enrichment. x The hydrogen is concentrated in D.

[0012] Another aspect of this disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and a pharmaceutically acceptable carrier or excipient. The pharmaceutical composition is useful for the treatment or prevention of disorders, diseases or conditions mediated by cereblon. The pharmaceutical composition may further comprise at least one additional pharmaceutical product.

[0013] In another aspect, the disclosure relates to a method for preparing cereblon in a biological sample, comprising contacting the sample with a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0014] Another aspect of the present disclosure relates to a method for inhibiting cereblon in a biological sample, comprising contacting the sample with a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0015] In another aspect, the disclosure relates to a method for modulating a target protein in a biological sample, comprising contacting the sample with a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0016] Another aspect of the present disclosure relates to a method for inhibiting a target protein in a biological sample, comprising contacting the sample with a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0017] Another aspect of the present disclosure is a method for inducing ubiquitination and degradation of a complex-associated protein selected from the group listed in Table 1 in a biological sample, which binds to and alters the specificity of a cereblon complex, comprising contacting the sample with a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0018] In another aspect, the Disclosure relates to a method for treating or preventing a cereblon-mediated disorder, disease, or condition in a subject, comprising administering a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0019] Another aspect of the present disclosure relates to a method for treating or preventing respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, and infectious diseases or disorders in a subject in need thereof, comprising administering a therapeutically effective dose of a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof to the subject.

[0020] In another aspect, the disclosure relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the preparation of a medicament for the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders and infectious diseases or disorders in subjects in need thereof.

[0021] Another aspect of this disclosure relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for the treatment or prevention of cancer.

[0022] In another aspect, the present disclosure relates to a method for degrading a target protein in a biological sample, comprising contacting a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the target protein is selected from the group listed in Table 1.

[0023] Another aspect of the present disclosure relates to a method for treating or preventing a target protein-mediated disorder, disease, or condition in a subject, comprising administering a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0024] In another aspect, the Disclosure relates to a method for treating or preventing cancer in a subject, comprising administering a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0025] Another aspect of this disclosure relates to the use of the compound of formula (I) or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers in the preparation of a medicament for treating or preventing a cerebromergic disorder, disease or condition in a subject requiring such treatment.

[0026] In another aspect, the disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment or prevention of a cerebroblasted disorder, disease or condition, in a subject requiring such treatment or prevention.

[0027] Another aspect of this disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment or prevention of cancer.

[0028] In another aspect, the disclosure relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the preparation of a medicament for the treatment or prevention of a target protein-mediated disorder, disease or condition in a subject.

[0029] Another aspect of this disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment or prevention of a target protein-mediated disorder, disease or condition in a subject. [Modes for carrying out the invention]

[0030] This disclosure relates to compounds and compositions that can modulate or inhibit target proteins by binding to and altering the specificity of cereblon complexes, thereby inducing ubiquitination and degradation of complex-associated proteins. This disclosure features a method for treating, preventing or improving cereblon-mediated disorders, diseases, or conditions by administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to a subject in need. The method of this disclosure can be used to treat a variety of cereblon-mediated disorders, diseases, or conditions by modulating target protein levels. Modulation of protein levels by degradation provides a novel approach to treating, preventing, or improving diseases including, but not limited to, respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, infectious diseases or disorders, and other cereblon-mediated disorders, diseases, or conditions.

[0031] In a first aspect of this disclosure, formula (I): [ka] (In the formula, R d1 、 R d2 and R d3(As stated above) Compounds or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers are described.

[0032] Details of this disclosure are described in the accompanying descriptions below. While similar or equivalent methods and materials may be used in the implementation or testing of this disclosure, only exemplary methods and materials are described here. Other features, purposes, and advantages of this disclosure will be apparent from the description and the claims. In this specification and the accompanying claims, singular nouns also include plural nouns unless the context explicitly indicates otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs. All patents and publications referenced herein are incorporated herein by reference as a whole.

[0033] Definitions of terms and rules used Terms not specifically defined herein should be given the meanings that a person skilled in the art would give them in consideration of this disclosure and the context. However, as used herein and in the appended claims, unless otherwise specified, the following terms have the meanings indicated and the following provisions shall be observed.

[0034] A. Chemical nomenclature, terminology, and rules In the groups, radicals, or substructures defined below, the number of carbon atoms is often specified before the group. For example, (C 1~10Alkyl refers to an alkyl group or radical having 1 to 10 carbon atoms. Generally, for groups containing two or more subgroups, the last group listed is the radical attachment site. For example, "alkylaryl" refers to a monovalent radical of the formula alkyl-aryl-, and "arylalkyl" refers to a monovalent radical of the formula aryl-alkyl-. Furthermore, where a divalent radical is appropriate, the use of terminology specifying a monovalent radical is interpreted as specifying the respective divalent radical, and vice versa. Unless otherwise specified, conventional definitions of terminology and conventional stable valencies can be estimated and achieved for all formulas and groups. The articles "a" and "an" refer to one or more (e.g., at least one) of the grammatical objects of the articles. For example, "element" refers to one or more elements.

[0035] The term "and / or" means "and" or "or" unless otherwise specified.

[0036] The term "optionally substituted" means that a given chemical substructure (e.g., an alkyl group) can (but is not required) be bonded to other substituents (e.g., heteroatoms). For example, an optionally substituted alkyl group may be a fully saturated alkyl chain (e.g., a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group may have substituents other than hydrogen. For example, it may be bonded to a halogen atom, a hydroxyl group, or any other substituent described herein at any point along the chain. Thus, the term "optionally substituted" means that a given chemical substructure may contain other functional groups, but does not necessarily have any further functional groups. Suitable substituents used in any substitution of the described groups include halogens, oxo, -OH, -CN, -COOH, -CH2CN, and -OC. 1~6 Alkyl, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 Haloalkyl, C 1~6 Haloalkoxy, -OC 2~6 Alkenyl, -OC2~6 Alkinyl, C 2~6 Alkenil, C 2~6 Alkynyl, -OH, -OP(O)(OH)2, -OC(O)C 1~6 Alkyl, -C(O)C 1~6 Alkyl, -OC(O)OC 1~6 Alkyl, NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-NHC(O)C 1~6 Alkyl, -C(O)NH(C 1~6 Alkyl), -S(O)2C 1~6 Alkyl, -S(O)NH(C 1~6 Alkyl) and S(O)N(C 1~6 This includes, but is not limited to, alkyl(2)2. Substituents can be optionally substituted themselves. As used herein, “optionally substituted” also means substituted or unsubstituted as defined below.

[0037] The term "substituted" means that a particular group or substructure has one or more suitable substituents, and that the substituents can bond to the particular group or substructure at one or more positions. For example, aryl substituted with cycloalkyl may indicate that the cycloalkyl is bonded to one aryl atom or fused with the aryl atom, sharing two or more common atoms.

[0038] The term "unsubstituted" means that the specified group does not have substituents.

[0039] Unless otherwise defined, "aryl" refers to a cyclic aromatic hydrocarbon group having one to three aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. If it contains two aromatic rings (e.g., bicyclic), the aromatic rings of the aryl group are optionally bonded at a single point (e.g., biphenyl) or fused at a single point (e.g., naphthyl). The aryl group is optionally substituted with one or more substituents, e.g., one to five substituents, at any attachment point. Exemplary substituents include -H, -halogen, -CN, and -OC. 1~6 Alkyl, C1~6 Alkyl, -O-C2~C6 alkenyl, -OC 2~6 Alkinyl, C 2~6 Alkenil, C 2~6 Alkynyl, -OH, -OP(O)(OH)2, -OC(O)C 1~6 Alkyl, -C(O)C 1~6 Alkyl, -OC(O)OC 1~6 Alkyl, NH2, NH(C 1~6 Alkyl), N(C 1~6 Alkyl)2,-S(O)2-C 1~6 Alkyl, -S(O)NHC 1~6 Alkyl and S(O)N(C) 1~6 This includes, but is not limited to, alkyl)2. Substituents can be optionally substituted themselves. Furthermore, if two fused rings are present, the aryl group may optionally have an unsaturated or partially saturated ring fused with a fully saturated ring. Exemplary ring systems of these aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenantrenyl, indanyl, indenyl, tetrahydronaphthalenyl, and tetrahydrobenzoannerenyl.

[0040] Unless otherwise specified, “heteroaryl” means a monovalent monocyclic aromatic radical or polycyclic aromatic radical of 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, O, or S, with the remaining ring atoms being C. As defined herein, heteroaryl is also a bicyclic aromatic heterocyclic group in which the heteroatoms are selected from N, O, and S. Aromatic radicals are optionally and independently substituted with one or more substituents as described herein. Examples include furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, and Midazo[1,2-b]pyrazolyl, flo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, indolyl, indolinyl, Indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, benzofuran, chromanil, thiochromanil, tetrahydroquinolinyl, dihydrobenzothiazine, dihydrobenzoxanil, quinolinil, isoquinolinyl, 1,6-naphthilidinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][1,6]naphthilidinyl, thieno[2,3-b]pyrazinyl, quinazo Linyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[1,2-a]pyridinyl, tetrahydropyrrolo[1,2-a]pyridinyl, 3,4-dihydro-2H-1Δ 2-Pyrrolo[2,1-b]pyrimidine, dibenzo[b,d]thiophene, pyridine-2-one, flo[3,2-c]pyridinyl, flo[2,3-c]pyridinyl, 1H-pyrido[3,4-b][1,4]thiadinyl, benzoxazolyl, benzoisoxazolyl, flo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthilidinyl, flo[3,2-b]pyridinyl, [1,2,4]triazolo[1,5-a]pyridinyl, benzo[1,2,3]triazolyl, imidazo[1,2,4]pyrimidine, [1,2,4]triazolo[4,3 This includes, but is not limited to, pyridazinyl (-b), benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazole, 1,3-dihydro-2H-benzo[d]imidazole-2-one, 3,4-dihydro-2H-pyrazolo[1,5-b][1,2]oxazinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, thiazolo[5,4d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3H-indolyl, and their derivatives. Furthermore, when comprising two fused rings, the aryl groups as defined herein may have an unsaturated or partially saturated ring fused with a fully saturated ring. Exemplary ring systems of these heteroaryl groups include indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, 3,4-dihydro-1H-isoquinolinyl, 2,3-dihydrobenzofuran, indolinyl, indolyl, and dihydrobenzoxanyl.

[0041] Halogen or "halo" refers to fluorine, chlorine, bromine, or iodine.

[0042] "Alkyl" refers to a saturated hydrocarbon that contains 1 to 12 carbon atoms, either in a straight or branched chain. 1~6 Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, and isohexyl.

[0043] "Alkoxy" refers to a straight-chain or branched-chain saturated hydrocarbon containing 1 to 12 carbon atoms, including a terminal "O" in the chain, such as -O(alkyl). Examples of alkoxy groups, but not limited to these, include methoxy, ethoxy, propoxy, butoxy, t-butoxy, or pentoxy groups.

[0044] An "alkenyl" refers to a straight-chain or branched unsaturated hydrocarbon containing 2 to 12 carbon atoms. An alkenyl group contains at least one double bond in its chain. The double bond of an alkenyl group can be unconjugated or conjugated to another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, n-butenyl, isobutenyl, pentenyl, or hexenyl. Alkenyl groups can be unsubstituted or substituted, and can be straight-chain or branched.

[0045] "Alkynyl" refers to a straight-chain or branched-chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. The "alkynyl" group contains at least one triple bond in the chain. Examples of alkenyl groups include ethynyl, propargyl, n-butynyl, isobutynyl, pentynyl, or hexynyl. Alkynyl groups can be unsubstituted or substituted.

[0046] "Alkylene" or "alkylenyl" means a divalent alkyl group. Any of the monovalent alkyl groups mentioned above may be alkylenes obtained by abstracting a second hydrogen atom from the alkyl group. As defined herein, alkylenes are C 1~6 It could also be alkylene. Alkylene is further C 1~4 It may be an alkylene. Typical alkylene groups include, but are not limited to, -CH2-, -CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH2CH(CH3)-, -CH2C(CH3)2-, -CH2CH2CH2-, and -CH2CH2CH2CH-.

[0047] "Cycloalkyl" or "carbocyclyl" refers to a monocyclic or polycyclic saturated or partially unsaturated carbocyclic ring containing 3 to 18 carbon atoms, where there are no delocalized n electrons (aromaticity) shared between the ring carbons. Examples of cycloalkyl groups include, but are not limited to, cyclopropenyl, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norboranyl, norborenyl, bicyclo[2.2.2]octanyl or bicyclo[2.2.2]octenyl and their derivatives. 3~8 Cycloalkyl groups are cycloalkyl groups containing 3 to 8 carbon atoms. Cycloalkyl groups can be fused (e.g., decalin) or cross-linked (e.g., norbornane).

[0048] "Hyperalkyl" refers to an alkyl group which further comprises at least one heteroatom (e.g., 1, 2, 3, or 4 heteroatoms) selected from oxygen, nitrogen, or sulfur, located within the parent chain (i.e., inserted between adjacent carbon atoms of the parent chain) and / or at one or more terminal positions. In certain embodiments, the heteroalkyl group is a saturated group having 1 to 10 carbon atoms and one or more heteroatoms in the parent chain ("heteroC"). 1~10 "Alkyl" refers to a saturated group having 1 to 9 carbon atoms and 1 or more heteroatoms in the parent chain ("hetero C 1~9 A heteroalkyl group is a saturated group having 1 to 8 carbon atoms and 1 or more heteroatoms in the parent chain ("hetero C 1~8 A heteroalkyl group is a saturated group having 1 to 7 carbon atoms and 1 or more heteroatoms in the parent chain ("hetero C 1~7 A heteroalkyl group is a saturated group having 1 to 6 carbon atoms and 1 or more heteroatoms in the parent chain ("hetero C 1~6 A heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms in the parent chain ("heteroC"). In some embodiments, a heteroalkyl group is a saturated group having 1 to 5 carbon atoms and 1 or 2 heteroatoms in the parent chain ("heteroC").1~5 A heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms in the parent chain ("heteroC"). In some embodiments, a heteroalkyl group is a saturated group having 1 to 4 carbon atoms and 1 or 2 heteroatoms in the parent chain ("heteroC"). 1~4 A heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom in the parent chain ("heteroC"). In some embodiments, a heteroalkyl group is a saturated group having 1 to 3 carbon atoms and 1 heteroatom in the parent chain ("heteroC"). 1~3 A heteroalkyl group is a saturated group having 1-2 carbon atoms and 1 heteroatom in the parent chain ("heteroC"). In some embodiments, a heteroalkyl group is a saturated group having 1-2 carbon atoms and 1 heteroatom in the parent chain ("heteroC"). 1~2 In some embodiments, the heteroalkyl group is a saturated group having one carbon atom and one heteroatom ("heteroC1 alkyl"). In some embodiments, the heteroalkyl group is a saturated group having 2 to 6 carbon atoms and one or two heteroatoms in the parent chain ("heteroC1 alkyl"). 2~6 The heteroalkyl group is an alkyl group. Unless otherwise specified, each example of a heteroalkyl group is either unsubstituted ("unsubstituted heteroalkyl group") or substituted with one or more substituents ("substituted heteroalkyl group"). In certain embodiments, the heteroalkyl group is an unsubstituted heteroalkyl group. 1~10 It is alkyl. In certain embodiments, the heteroalkyl group is a substituted heteroC 1~10 It is alkyl.

[0049] A "heterocyclyl" is a saturated or partially saturated monocyclic or polycyclic ring comprising carbon and at least one heteroatom selected from oxygen, nitrogen, or sulfur (O, N, or S), wherein there are no delocalized n electrons (aromatic) shared between the ring carbons or heteroatoms. The heterocycloalkyl ring structure can be substituted with one or more substituents. Substituents can be optionally substituted themselves. Examples of heterocyclyl rings include, but are not limited to, oxetanil, azetadinil, tetrahydrofuranil, tetrahydropyranil, pyrrolidinil, oxazolinil, oxazolidinil, thiazolinil, thiazolidinil, pyranil, thiopyranil, tetrahydropyranil, dioxalinil, piperidinil, morpholinil, thiomorpholinil, thiomorpholinil S-oxide, thiomorpholinil S-dioxide, piperazinil, azepinil, oxepinil, diazepinil, tropanil, oxazolidinonil, 1,4-dioxanil, dihydrofuranil, 1,3-dioxolanil, imidazolidinil, imidazolinil, dithiolanil, and homotropanil.

[0050] "Hydroxyalkyl" refers to an alkyl group that is substituted with one or more -OH groups. Examples of hydroxyalkyl groups include HO-CH2-, HO-CH2CH2-, and CH2-CH(OH)-.

[0051] "Haloalkyl" refers to an alkyl group substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, and trichloromethyl.

[0052] "Haloalkoxy" refers to an alkoxy group substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethoxy, difluoromethoxy, pentafluoroethoxy, and trichloromethoxy.

[0053] "Cyano" refers to a substituent that has a carbon atom bonded to a nitrogen atom by a triple bond. For example, C≡N.

[0054] "Amino" refers to a substituent (e.g., NH2) that contains at least one nitrogen atom.

[0055] "Alkylamino" refers to an amino or NH2 group in which one of the hydrogen atoms is replaced by an alkyl group, such as -NH(alkyl). Examples of alkylamino groups include, but are not limited to, methylamino (e.g., -NH(CH3)), ethylamino, propylamino, isopropylamino, n-butylamino, sec-butylamino, and tert-butylamino.

[0056] "Dialkylamino" refers to an amino or NH2 group in which both hydrogens are substituted with an alkyl group, e.g., -N(alkyl)2. The alkyl groups of the amino group may be the same or different alkyl groups. Examples of dialkylamino groups include, but are not limited to, dimethylamino (e.g., -N(CH3)2), diethylamino, dipropylamino, diisopropylamino, di-n-butylamino, di-sec-butylamino, di-tert-butylamino, methyl(ethyl)amino, and methyl(butylamino).

[0057] A "spirocarbocyclyl" refers to a carbocyclyl bicyclic ring system in which both rings are connected via a single atom. The rings may differ in size and properties, or they may be the same in size and properties. Examples include spiropentane, spirohexane, spiroheptane, spirooctane, spirononane, or spirodecane. One or both rings of a spiro ring can be fused to a carbocyclic, heterocyclic, aromatic, or heteroaromatic ring of another ring. 3~12 Spirocycloalkyl groups are spiro rings containing 3 to 12 carbon atoms.

[0058] "Spiroheterocycloalkyl" or "spiroheterocyclyl" means a spirocarbocyclyl in which at least one of the rings is heterocyclic and one or more carbon atoms may be substituted with heteroatoms (for example, one or more carbon atoms may be substituted with heteroatoms in at least one ring). One or both rings of a spiroheterocyclic ring can be fused to a carbocyclic, heterocyclic, aromatic, or heteroaromatic ring of another ring.

[0059] B. Terminology and Rules for Salts, Prodrugs, Derivatives, and Solvates A “prodrug” or “prodrug derivative” refers to a covalent derivative or carrier of a parent compound or active drug that undergoes at least some degree of in vivo modification before exhibiting its pharmacological effect. Generally, such prodrugs have metabolically cleavable groups that are rapidly converted in vivo, for example, by hydrolysis in the blood, to produce the parent compound, and generally include ester and amide analogs of the parent compound. Prodrugs are formulated to improve chemical stability, improve patient acceptance and compliance, improve bioavailability, extend duration of action, improve organ selectivity, improve formulation (e.g., increased water solubility), and / or reduce side effects (such as toxicity). Generally, prodrugs themselves have weak or no biological activity and are stable under normal conditions.Prodrugs are known in the art through methods well known in this field, for example, Chapter 5 of "Design and Applications of Prodrugs" in *A Textbook of Drug Design and Development*, Krogsgaard-Larsen and H. Bundgaard (eds.), Gordon & Breach, 1991; *Design of Prodrugs*, H. Bundgaard (ed.), Elsevier, 1985; *Prodrugs: Topical and Ocular Drug Delivery*, KBSloan (ed.), Marcel Dekker, 1998; *Methods in Enzymology*, K. Widder et al. (eds.), Vol. 42, Academic Press, 1985, especially pp. 309-396; and *Burger's Medicinal Chemistry and Drug Discovery*, 5th Ed., M. Wolff (ed.), John These can be easily prepared from parent compounds using methods such as those described in Wiley & Sons, 1995, particularly Vol. 1 and pp. 172-178 and pp. 949-982; Pro-Drugs as Novel Delivery Systems, T. Higuchi and V. Stella (eds.), Am. Chem. Soc., 1975; and Bioreversible Carriers in Drug Design, E.B. Roche (ed.), Elsevier, 1987, and the entire contents of each of these are incorporated herein by reference.

[0060] As used herein, “pharmaceutically acceptable prodrug” means a prodrug of the compounds disclosed herein that, within the bounds of sound medical judgment, is suitable for use in contact with human and lower animal tissues without excessive toxicity, irritation, allergic reactions, and similar effects, is commensurate with a reasonable benefit / risk ratio, and is effective for its intended use as, where possible, as the amphoteric form.

[0061] "Salt" means the product of a reaction between a parent compound and a parent compound having an ionic form of the parent compound, or a parent acid or base suitable for forming an ionic form of the parent compound, or a basic salt of the parent compound. Salts of the compounds of this disclosure can be synthesized from parent compounds containing basic or acidic substructures by conventional chemical methods. Generally, salts are prepared by reacting a free base or acidic parent compound with a stoichiometric amount or excess of the desired salt-forming inorganic or organic acid or base in a suitable solvent or a variety of solvent combinations.

[0062] "Pharmacologically acceptable salt" means a salt of the compounds of this disclosure that, within the bounds of sound medical judgment, is suitable for use in contact with human and lower animal tissues without excessive toxicity, irritation, allergic reactions, and similar effects, is commensurate with a reasonable benefit / risk ratio, is typically water-soluble or oil-soluble or dispersible, and is effective for its intended use. This term includes pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. Since the compounds of this disclosure are useful in both free base and salt forms, the use of salt forms is practically equivalent to the use of base forms. A list of suitable salts can be found, for example, SMBirge et al., J.Pharm.Sci., 1977, 66, pp.1-19, the entire contents of which are incorporated herein by reference.

[0063] "Pharmacologically acceptable acid addition salts" are salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, nitric acid, phosphoric acid and similar substances, that retain the biological efficacy and properties of the free base and are not biologically or otherwise undesirable, as well as acetic acid, trichloroacetic acid, trifluoroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 2-acetoxybenzoic acid, butyric acid, camphoric acid, camphasulfonic acid, cinnamic acid, citric acid, digluconic acid, ethanesulfonic acid, glutamic acid, glycolic acid, glycerophosphate, hemisulfate, heptamine. These are salts formed from organic acids such as nic acid, hexanoic acid, formic acid, fumaric acid, 2-hydroxyethanesulfonic acid (isethionic acid), lactic acid, maleic acid, hydroxymaleic acid, malic acid, malonic acid, mandelic acid, mesitylenesulfonic acid, methanesulfonic acid, naphthalenesulfonic acid, nicotinic acid, 2-naphthalenesulfonic acid, oxalic acid, pamoic acid, pectinic acid, phenylacetic acid, 3-phenylpropionic acid, picric acid, pivalic acid, propionic acid, pyruvic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, sulfanilic acid, tartaric acid, p-toluenesulfonic acid, undecanoic acid, and similar substances.

[0064] "Pharmacologically acceptable base addition salts" means salts formed with ammonia or ammonia hydroxide, carbonate or bicarbonate or inorganic bases such as sodium, potassium, lithium, calcium, magnesium, iron, zinc, copper, manganese, aluminum and the like, that retain the biological efficacy and properties of the free acid and are not biologically or otherwise undesirable. Ammonium, potassium, sodium, calcium and magnesium salts are particularly preferred. Salts derived from pharmaceutically acceptable organic non-toxic bases include primary, secondary and tertiary amines, quaternary amine compounds, substituted amines including naturally occurring substituted amines, cyclic amines and methylamines, dimethylamine, trimethylamine, ethylamine, diethylamine, triethylamine, isopropylamine, tripropylamine, tributylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, hydravamine, This includes salts of basic ion exchange resins such as choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, tetramethylammonium compounds, tetraethylammonium compounds, pyridine, N,N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, dicyclohexylamine, dibenzylamine, N,N-dibenzylphenethylamine, 1-ephenamine, N,N'-dibenzylethylenediamine, polyamine resins, and the like. Particularly preferred organic non-toxic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

[0065] A “solvate” refers to a variable stoichiometric complex formed by a solute, e.g., a compound of formula (I), and a solvent, e.g., water, ethanol, or acetic acid. This physical bonding can include varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain examples, the solvate is separable, for example, if one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. Generally, such solvents selected for the purposes of disclosure do not impede the biological activity of the solute. Solvates include both liquid-phase solvates and separable solvates. Representative solvates include hydrates, ethanolates, methanolates, and similar compounds.

[0066] A "hydrate" refers to a solvate in which the solvent molecule is water.

[0067] The compounds of the present disclosure discussed below include their free bases or acids, their salts, solvates, and prodrugs, which may include sulfur oxide atoms or nitrogen quaternide atoms in their structures, particularly in pharmaceutically acceptable forms, unless otherwise specified or indicated. Such forms, particularly in pharmaceutically acceptable forms, are intended to be included in the appended claims.

[0068] C. Terminology and rules for isomers An "isomer" refers to a compound that has the same number and type of atoms, and therefore the same molecular weight, but differs in the arrangement or structure of its atoms in space. This term includes stereoisomers and geometric isomers.

[0069] "Stereoisomer" or "optical isomer" means a stable isomer having at least one chiral atom or restricted rotation, resulting in a vertically asymmetric plane (e.g., certain biphenyl, allene, spiro compounds, etc.) that can rotate plane-polarized light. Because the compounds of this disclosure have chiral centers and other chemical structures that may result in stereoisomerism, this disclosure assumes stereoisomers and mixtures thereof. The compounds of this disclosure and their salts contain chiral carbon atoms and therefore may exist as single stereoisomers, racemates, and mixtures of enantiomers and diastereomers. Typically, such compounds are prepared as racemic mixtures. However, if necessary, such compounds may be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers or diastereomers, or as stereoisomer-enriched mixtures. As will be described in more detail below, individual stereoisomers of a compound are synthesized from optically active starting materials containing the desired chiral center, or prepared by separation or recrystallization of a mixture of enantiomers after conversion to a diastereomer mixture, using chromatographic techniques, chiral resolving agents, or direct separation of enantiomers in a chiral chromatography column. Starting compounds with specific stereochemistrys are commercially available or prepared by the methods described below and decomposed by techniques well known in the art.

[0070] An "enantiomer" refers to a pair of stereoisomers that are mirror images of each other but cannot be superimposed.

[0071] "Diastereoisomers" or "diastereomers" refer to optical isomers that are not mirror images of each other.

[0072] A "racemic mixture" or "racemic mixture" refers to a mixture containing equal amounts of individual enantiomers.

[0073] A "non-racemic mixture" refers to a mixture containing unequal amounts of individual enantiomers.

[0074] A “geometric isomer” is a stable isomer whose rotational freedom is restricted by a double bond (e.g., cis-2-butene and trans-2-butene) or a cyclic structure (e.g., cis-1,3-dichlorocyclobutane and trans-1,3-dichlorocyclobutane). Since carbon-carbon double (olefin) bonds, C=N double bonds, cyclic structures and similar structures may be present in the compounds of this disclosure, this disclosure intends to describe each of the various stable geometric isomers and mixtures thereof arising from the arrangement of substituents around these double bonds and within these cyclic structures. Substituents and isomers are indicated using the conventional cis / trans method or the E or Z scheme. The term “E” means a higher-order substituent on the opposite side of the double bond, and the term “Z” means a higher-order substituent on the same side of the double bond. A detailed discussion of E and Z isomerism is provided in J. March, Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed., John Wiley & Sons, 1992, the entire contents of which are incorporated herein by reference. Some of the following examples represent a single E isomer, a single Z isomer, and an E / Z isomer mixture. The determination of E and Z isomerism is performed by X-ray crystallography. 1 1H NMR and 13 This can be done using analytical methods such as 13C NMR.

[0075] Some of the compounds of this disclosure may exist in two or more tautomer forms. As stated above, the compounds of this disclosure include all such tautomers.

[0076] It is well known in the art that the biological and pharmacological activity of a compound is highly sensitive to its stereochemistry. Therefore, enantiomers often exhibit significantly different biological activities, including differences in pharmacokinetic properties such as metabolism and protein binding, as well as differences in pharmacological properties such as the type, degree, and toxicity of the activity exhibited. Accordingly, those skilled in the art will understand that one enantiomer may be more active or exhibit superior effects when concentrated compared to or separated from another enantiomer. Furthermore, those skilled in the art will know, from the knowledge of this disclosure and the prior art, methods for separating, concentrating, or selectively preparing enantiomers of the compounds of this disclosure.

[0077] Therefore, while it may be possible to use racemic drugs, they are often less effective than administering the same amount of enantiomerically pure drugs. In fact, arbitrarily, one enantiomer may be pharmacologically inactive and simply serve as a diluent. For example, ibuprofen was once administered as a racemic mixture, but only the S-isomer of ibuprofen has been shown to be effective as an anti-inflammatory agent (however, in the case of ibuprofen, the R-isomer is inactive, but it is converted to the S-isomer in vivo, so the rate of action of the racemic drug is lower than that of the pure S-isomer). Furthermore, the pharmacological activity of enantiomers may have distinct biological activity. For example, S-penicillamine is a treatment for chronic arthritis, while R-penicillamine is toxic. In fact, some purified enantiomers have advantages over racemic mixtures, as purified individual isomers have been reported to have faster transdermal penetration rates compared to racemic mixtures. See U.S. Patent No. 5,114,946 and No. 4,818,541.

[0078] Therefore, if one enantiomer is pharmacologically more active, less toxic, or has more favorable properties in the body than another, it would be therapeutically more beneficial to administer that enantiomer preferentially. In this way, the patient receiving treatment will receive a lower total dose of the drug and a lower dose of the enantiomer than that which is potentially toxic or an inhibitor of the other enantiomer.

[0079] The preparation of pure enantiomers or mixtures with a desired enantiomer excess (ee) or enantiomer purity can be achieved by (a) separation or resolution of the enantiomers, or (b) one or more of the many methods of enantioselective synthesis or combinations thereof that are well known to those skilled in the art. These resolution methods generally rely on chiral recognition and include, for example, chromatography using a chiral stationary phase, enantioselective host-guest complex formation, decomposition or synthesis using chiral auxiliaries, enantioselective synthesis, enantioselective and non-enzymatic kinetic resolution, or spontaneous enantioselective crystallization. Such methods are generally described in Chiral Separation Techniques: A Practical Approach (2nd Ed.), G. Subramanian (ed.), Wiley-VCH, 2000; TE Beesley and RPS Scott, Chiral Chromatography, John Wiley & Sons, 1999; and Satinder Ahuja, Chiral Separations by Chromatography, Am. Chem. Soc., 2000. Furthermore, there are equally well-known methods for quantifying enantiomer excess or purity using methods such as GC, HPLC, CE, or NMR, and for assigning absolute configuration and conformation using methods such as CD ORD, X-ray crystallography, or NMR.

[0080] Generally, unless a specific stereochemistry or isomer is specifically indicated by the compound name or structure, all tautomers, isomers, and mixtures are intended, whether they are chemical structures, individual geometric isomers or stereoisomers of a compound, or racemic or non-racemic mixtures.

[0081] D. Terminology and regulations relating to the administration and treatment of pharmaceuticals The “patient” or “subject” is a mammal, such as a human, mouse, rat, guinea pig, dog, cat, horse, cattle, pig, or a non-human primate such as a monkey, chimpanzee, baboon, or rhesus macaque. In certain embodiments, the subject is a primate. In yet other embodiments, the subject is a human.

[0082] When used in relation to a compound, “effective amount” or “therapeutic effective amount” means the amount of the compound of this disclosure. (i) to treat or prevent a particular disease, condition or disorder; (ii) to alleviate, improve or eliminate one or more symptoms of a particular disease, condition or disorder; or (iii) to prevent or delay the onset of one or more symptoms of a particular disease, condition or disorder as described herein.

[0083] The terms “pharmaceutical effective dose” or “therapeutic effective dose” mean the amount of the compound according to this disclosure that, when administered to a patient in need, is sufficient to treat a disease condition, state, or disorder for which the compound is useful. Such a dose would be sufficient to elicit the desired biological or medical response from the tissue, system, or patient as sought by the researcher or clinician. The amount of the compound according to this disclosure that constitutes a therapeutic effective dose varies depending on the compound and its biological activity, the composition used for administration, the time of administration, the route of administration, the rate of excretion of the compound, the duration of treatment, the type and severity of the disease condition or disorder being treated, drugs used in combination with or concurrently with the compound according to this disclosure, and factors such as age, weight, general condition, sex, and diet of the patient. Such a therapeutic effective dose can be routinely determined by a person skilled in the art, taking into account their own knowledge, prior art, and this disclosure.

[0084] As used herein, the term “pharmaceutical composition” refers to the compound of the present disclosure or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, together with at least one pharmaceutically acceptable carrier in a form suitable for oral or parenteral administration.

[0085] "Carrier" means a material, composition, or medium, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, that includes a carrier, excipient, and diluent, and is involved in the transport or delivery of a pharmaceutical product from one organ or part of the body to another organ or part of the body of the target.

[0086] If such subject derives a biological, medical, or other benefit in quality of life from such treatment (preferably in humans), then the subject "needs" the treatment.

[0087] As used herein, the terms “inhibit,” “inhibit,” or “inhibiting” refer to a reduction or suppression of a given condition, symptom, disorder, or disease, or a significant decrease in the basic activity of a biological activity or biological process.

[0088] As used herein, the terms “to treat,” “treat,” or “treat” any disease or disorder indicate that the disease or disorder is being alleviated or improved (i.e., slowing or halting the progression of at least one of the disease or its clinical symptoms); or that at least one physical parameter or biomarker associated with the disease or disorder, including those that may not be recognizable to the patient.

[0089] As used herein, the terms “preventing,” “preventing,” or “prevention” of any disease or disorder indicate a preventive measure for the disease or disorder or a delay in the onset or progression of the disease or disorder.

[0090] "Pharmacologically acceptable" means that a substance or composition must be chemically and / or toxicologically compatible with the other components of the preparation and / or the mammal treated therewith.

[0091] Unless otherwise specified, "disability" means, and is used synonymously with, the terms disease, condition, or illness.

[0092] "Administer," "administering," or "administering" means directly administering the disclosed compound or a pharmaceutically acceptable salt of the disclosed compound or composition to a subject, or administering a prodrug derivative of the compound, or an analog or compound of the compound, or a pharmaceutically acceptable salt of the composition, that can form an equal amount of the active compound in the subject's body.

[0093] A "prodrug" is a compound that can be converted in vivo to a disclosed compound by metabolic means (e.g., by hydrolysis).

[0094] "The Compounds of the Disclosure," "The Compound of Formula (I)," "The Disclosed Compounds," and equivalent expressions (unless otherwise specified) are formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Ia f), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), and (Iam), tautomers, prodrugs, salts, especially pharmaceutically acceptable salts thereof, and their solvates and hydrates, as described herein, means all stereoisomers (including diastereoisomers and enantiomers), rotational isomers, tautomers, and isotope-labeled compounds (including deuterium substitutions) and uniquely formed substructures (e.g., polymorphs, solvates, and / or hydrates), to the extent permitted by the context. For the purposes of this disclosure, solvates and hydrates are generally considered to be compositions. Generally and preferably, the compounds of this disclosure and the formulas designating the compounds of this disclosure are understood to include only the stable compounds and exclude the unstable compounds, even if the unstable compounds are considered to be literally included by the compound formula. Similarly, references to intermediates, whether asserted themselves or not, mean to include their salts and solvates, to the extent permitted by the context. For clarity, specific examples may be given in the text where the context allows, but these examples are merely for the purpose of facilitating understanding and are not intended to exclude other examples where the context allows.

[0095] "Stable compound" or "stable structure" means a compound that is strong enough to withstand isolation from a reaction mixture to a useful purity and formulation design for an effective therapeutic or diagnostic agent. For example, compounds having a "dangling value" or being a carbanion are not compounds intended by this disclosure.

[0096] The compounds provided are CRBN binders and are therefore useful for treating one or more disorders associated with the activity of CRBN or its variants. Accordingly, in certain embodiments, the Disclosure provides a method for treating a CRBN-mediated disorder, comprising the step of administering the compounds of the Disclosure or a pharmaceutically acceptable composition thereof to a patient in need.

[0097] As used herein, the term “CRBN-mediated” disorder, disease and / or condition means any disease, condition or disorder in which CRBN or its variants are known to play a role. Therefore, another embodiment relates to a treatment for preventing one or more diseases in which CRBN or its variants are known to play a role. Such CRBN-mediated disorders include, but are not limited to, respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, or infectious diseases or disorders.

[0098] In certain embodiments, the terms “about” or “approximately” mean within 20%, preferably within 10%, and more preferably within 5% of a given value or range.

[0099] The yields for each reaction described herein are expressed as a percentage of the theoretical yield.

[0100] D. Specific embodiments and methods for testing compounds of formula (I) This disclosure relates to a compound or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, which is useful for treating or preventing diseases and disorders related to the regulation of protein levels via binding to the cereblon complex and alteration of specificity to induce proteasome-mediated degradation of selected proteins. This disclosure further relates to a compound or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, which is useful for treating or preventing diseases and disorders related to the reduction or decrease of protein levels via binding to the cereblon complex and alteration of specificity to induce proteasome-mediated degradation of selected proteins.

[0101] In one embodiment, the compound of formula (I) is [ka] [ka] [ka] Or it may have pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, and tautomers thereof.

[0102] The above formulas (i.e., formula (I), formula (Ia), formula (Ib), formula (Ic), formula (Id), formula (Ie), formula (If), formula (Ig), formula (Ih), formula (Ii), formula (Ij), formula (Ik), formula (Il), formula (Im), formula (In), formula (Io), formula (Ip), formula (Iq), formula (Ir), formula (Is), formula (Lith), formula (Iu) In some embodiments of formulas (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), and / or (Iam)), [ka] This is a double bond. In another embodiment, [ka] It is a single bond.

[0103] In some embodiments of the above formula, R d1 is -CH2OC(O)R 15 -CH2OP(O)OHOR 15 Or CH2OP(O)(R 15 )2. In another embodiment, R d1 H, -CH2OC(O)R 15 or -CH2OP(O)OHOR 15 In yet another embodiment, R d1 H, -CH2OC(O)R 15 or -CH2OP(O)(R 15 )2. In another embodiment, R d1 H, -CH2OP(O)OHOR 15 or -CH2OP(O)(R 15 )2. In yet another embodiment, R d1 is H or -CH2OC(O)R 15 In another embodiment, R d1 is H or -CH2OP(O)OHOR 15 In yet another embodiment, R d1 is H or -CH2OP(O)(R 15 )2. In another embodiment, R d1 H is H.

[0104] In some embodiments of the above formula, R d2 H, C 1~3 Alkyl, halogen, C 1~3 Haloalkyl or C 1~3 It is heteroalkyl. In another embodiment, R d2 H, C 1~3 Alkyl, halogen, or C 1~3 In yet another embodiment, R d2 H, C1~6 Alkyl, halogen, or C 1~6 It is heteroalkyl. In another embodiment, R d2 H, C 1~6 Alkyl, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl. In yet another embodiment, R d2 H, halogen, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl. In another embodiment, R d2 H, C 1~6 It is alkyl or halogen. In yet another embodiment, R d2 H, C 1~6 Alkyl or C 1~6 In another embodiment, R d2 H, C 1~6 Alkyl or C 1~6 It is heteroalkyl. In yet another embodiment, R d2 is H or a halogen. In yet another embodiment, R d2 is H or C 1~6 In another embodiment, R d2 is H or C 1~6 It is heteroalkyl. In yet another embodiment, R d2 is H or C 1~6 It is alkyl. In another embodiment, R d2 is H or C 1~3 It is alkyl. In yet another embodiment, R d2 is H, methyl, ethyl, n-propyl, or i-propyl. In another embodiment, R d2 is H, methyl, or ethyl. In yet another embodiment, R d2 is H or methyl. In another embodiment, R d2 is H, methyl, or F. In yet another embodiment, R d2 H is H.

[0105] In some embodiments of the above formula, R d3 teeth, [ka] [ka] [ka] That is the case.

[0106] In another embodiment, R d3 teeth, [ka] [ka] That is the case.

[0107] In another embodiment, R d3 teeth, [ka] [ka] [ka] That is the case.

[0108] In another embodiment, R d3 teeth, [ka] That is the case.

[0109] In another embodiment, R d3 teeth, [ka] That is the case.

[0110] In another embodiment, R d3 teeth, [ka] That is the case.

[0111] In another embodiment, R d3 teeth, [ka] That is the case.

[0112] In another embodiment, R d3 teeth, [ka] That is the case.

[0113] In another embodiment, R d3 teeth, [ka] That is the case.

[0114] In another embodiment, R d3 teeth, [ka] That is the case.

[0115] In another embodiment, R d3 teeth, [ka] That is the case.

[0116] In another embodiment, R d3 teeth, [ka] That is the case.

[0117] In another embodiment, R d3 teeth, [ka] That is the case.

[0118] In another embodiment, R d3 teeth, [ka] That is the case.

[0119] In another embodiment, R d3 teeth, [ka] That is the case.

[0120] In another embodiment, R d3 teeth, [ka] That is the case.

[0121] In another embodiment, R d3 teeth, [ka] That is the case.

[0122] In another embodiment, R d3 teeth, [ka] [ka] [ka] [ka] [ka] That is the case.

[0123] In another embodiment, R d3 teeth, [ka] [ka] [ka] [ka] [ka] That is the case.

[0124] In another embodiment, R d3 teeth, [ka] That is the case.

[0125] In another embodiment, R d3 teeth, [ka] That is the case.

[0126] In another embodiment, R d3 teeth, [ka] That is the case.

[0127] In another embodiment, R d3 teeth, [ka] [ka] [ka] That is the case.

[0128] In another embodiment, R d3 teeth, [ka] [ka] [ka] That is the case.

[0129] In another embodiment, R d3 teeth, [ka] [ka] [ka] [ka] [ka] That is the case.

[0130] In another embodiment, R d3 teeth, [ka] [ka] [ka] [ka] [ka] That is the case.

[0131] In another embodiment, R d3 teeth, [ka] [ka] [ka] [ka] [ka] That is the case.

[0132] In another embodiment, R d3 teeth, [ka] [ka] [ka] [ka] [ka] That is the case.

[0133] In another embodiment, R d3 teeth, [ka] [ka] [ka] That is the case.

[0134] In another embodiment, R d3 teeth, [ka] [ka] [ka] That is the case.

[0135] In another embodiment, R d3 teeth, [ka] That is the case.

[0136] In another embodiment, R d3 teeth, [ka] That is the case.

[0137] In another embodiment, R d3 teeth, [ka] That is the case.

[0138] In some embodiments of the above formula, A 1 This is a 5- or 6-membered heterocycline or N,NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 2 R 1d It is a 5-membered heteroaryl substituted with A. In another embodiment, A 1 This is a 5- or 6-membered heterocycline or N,NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k , a 5-membered heteroaryl comprising 1 to 3 additional heteroatoms selected from O and S. In yet another embodiment, A 1 This is a 5-membered heterocycline or N,NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 3 R 1d It is a 5-membered heteroaryl substituted with A. In another embodiment, A 1 This is a 5-membered heterocycline or N,NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k , a 5-membered heteroaryl comprising 1 to 3 additional heteroatoms selected from O and S. In yet another embodiment, A1 This is a 6-membered heterocycline or N,NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 3 R 1d It is a 5-membered heteroaryl substituted with A. In another embodiment, A 1 This is a 6-membered heterocycline or N,NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k It is a 5-membered heteroaryl compound that optionally contains 1 to 3 additional heteroatoms selected from O and S.

[0139] In another embodiment, A 1 N, NR 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 2 R 1d It is a 5 or 6-membered heterocycline that is substituted with A. In another embodiment, A 1 N, NR 1k , a 5 or 6-membered heterocycline optionally comprising 1 to 3 additional heteroatoms selected from O and S. In yet another embodiment, A 1 N, NR 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 3 R 1d It is a 5-membered heterocycline that is substituted with A. In another embodiment, A 1 N, NR 1k , a 5-membered heterocycline optionally comprising 1 to 3 additional heteroatoms selected from O and S. In yet another embodiment, A 1 N, NR 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 3 R 1d It is a 6-membered heterocycline that is substituted with A. In another embodiment, A 1 N, NR 1k It is a 6-membered heterocycline that optionally contains 1 to 3 additional heteroatoms selected from O and S.

[0140] In another embodiment, A 1 N, NR 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 3 R 1d It is a 5-membered heteroaryl substituted with A. In another embodiment, A 1 N, NR 1k It is a 5-membered heteroaryl compound that optionally contains 1 to 3 additional heteroatoms selected from O and S.

[0141] In some embodiments of the above formula, A 2 C 5~7 Carbocyclyl or N, NR 1k , a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O and S, and carbocykrill and heterocyclyl contain 1-3 R 1d It has been replaced with.

[0142] In some embodiments of the above formula, X 1 , NR 4 In another embodiment, X 1 S is.

[0143] In some embodiments of the above formula, X 2 CR 1a Or N. In another embodiment, X 2 CR 1a In yet another embodiment, X 2 It is N.

[0144] In some embodiments of the above formula, X 2a CR 1a Or N. In another embodiment, X 2a CR 1a In yet another embodiment, X 2a It is N.

[0145] In some embodiments of the above formula, X 2 CR 1a or N, X 2a CR 1aIn another embodiment, X 2 CR 1a or N, X 2a In yet another embodiment, X 2a CR 1a or N, X 2 CR 1a In another embodiment, X 2a CR 1a or N, X 2 In yet another embodiment, X 2a CR 1a X 2 In another embodiment, X 2a N is X 2 In yet another embodiment, X 2a CR 1a X 2 It is N.

[0146] In some embodiments of the above formula, each X 3 CR is independent. 1d or N; two or fewer X 3 It is N.

[0147] In some embodiments of the above formula, each X 3’ CR is independent. 1d , CR 1c or N, and two or fewer X 3 is N and at least one X 3’ CR 1c In another embodiment, each X 3’ CR is independent. 1d or CR 1c and at least one X 3’ CR 1c In another embodiment, each X 3’ CR is independent. 1c or N, and two or fewer X 3 It is N.

[0148] In some embodiments of the above formula, each X 4CR is independent. 1d or N, and at least one X 4 is N, and there are two or fewer X 4 It is N.

[0149] In some embodiments of the above formula, each X 5 CR is independent. 1a or N; two or fewer X 5 It is N.

[0150] In some embodiments of the above formula, X 6 , NR 1k Or O. In another embodiment, X 6 , NR 1k Or S. In yet another embodiment, X 6 is O or S. In another embodiment, X 6 , NR 1k In yet another embodiment, X 6 In another embodiment, X 6 S is.

[0151] In some embodiments of the above formula, X 7 , NR 4 Or O. In another embodiment, X 7 N, NR 4 Or S. In yet another embodiment, X 7 is O or S. In another embodiment, X 7 , NR 4 In yet another embodiment, X 7 In another embodiment, X 7 S is.

[0152] In some embodiments of the above formula, R 1a C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3Alkyl)2,-CN,F, orCl. In another embodiment, R 1a H, C 2~4 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In yet another embodiment, R 1a H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy or C 1~3 In another embodiment, R 1a C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy or C 1~3 In yet another embodiment, R 1a -NH2, -NH(C 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In another embodiment, R 1a H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1a C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1a H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1a C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3In another embodiment, R 1a H, C 1~3 Alkyl, C 1~3 Haloalkyl, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In yet another embodiment, R 1a C 1~3 Alkyl, C 1~3 Haloalkyl, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In another embodiment, R 1a H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 It is alkyl)2 or -CN. In yet another embodiment, R 1a C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 It is alkyl)2 or -CN. In another embodiment, R 1a H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1a C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1a H, C 1~3 Alkyl, C 1~3 In yet another embodiment, R 1a C 1~3 Alkyl, C 1~3It is a haloalkyl or F.

[0153] In some embodiments of the above formula, R 1b C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In another embodiment, R 1b H, C 2~4 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In yet another embodiment, R 1b H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy or C 1~3 In another embodiment, R 1b C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy or C 1~3 In yet another embodiment, R 1b -NH2, -NH(C 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In another embodiment, R 1b H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1b C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1b H, C1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1b C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1b H, C 1~3 Alkyl, C 1~3 Haloalkyl, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In yet another embodiment, R 1b C 1~3 Alkyl, C 1~3 Haloalkyl, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl. In another embodiment, R 1b H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 It is alkyl)2 or -CN. In yet another embodiment, R 1b C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 It is alkyl)2 or -CN. In another embodiment, R 1b H, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1b C 1~3 Alkyl, C 1~3 Haloalkyl, C1~3 Alkoxy, C 1~3 In another embodiment, R 1b H, C 1~3 Alkyl, C 1~3 In yet another embodiment, R 1b C 1~3 Alkyl, C 1~3 It is a haloalkyl or F.

[0154] In some embodiments of the above formula, R 1c C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by R. In another embodiment, 1c C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4-C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is being replaced by an arbitrary choice.

[0155] In another embodiment, R 1c is, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7-NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, carbocyclyls, heterocyclyls, aryls, and heteroaryls are 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0156] In another embodiment, R 1c C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Haloalkyl, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0157] In some embodiments of the above formula, R 1c’ C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, F, Cl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2)0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7-NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, where the alkynyl is optionally substituted with 1 to 3 R2s, and carbocyclyls, heterocyclyls, aryls, and heteroaryls have 1 to 5 R2s. 5 It is optionally replaced by R. In another embodiment, 1c’ C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, F, Cl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is being replaced by an arbitrary choice.

[0158] In another embodiment, R 1c’ is, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, carbocyclyls, heterocyclyls, aryls, and heteroaryls are 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0159] In another embodiment, R 1c’ C 1~6 Alkyl, C 2~6 Alkinyl, C1~6 Haloalkyl, F, Cl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0160] In some embodiments of the above formula, R 1d H, C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by R. In another embodiment, 1d H, C 1~6 Alkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is being replaced by an arbitrary choice.

[0161] In another embodiment, R 1d H, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, carbocyclyls, heterocyclyls, aryls, and heteroaryls are 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0162] In another embodiment, R 1d H, C 1~6 Alkyl, C 2~6 Alkinyl, C 1~6 Haloalkyl, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6-5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R5 It is being replaced by an arbitrary choice.

[0163] In some embodiments of the above formula, R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 It is an alkoxy, -CN, F, or Cl. In yet another embodiment, R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 In another embodiment, R 1e C 2~3 Alkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1e C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1e C 2~3 Alkyl, C1~3 In another embodiment, R 1e C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1e C 2~3 Alkyl, C 1~3 It is a haloalkyl, F, or Cl.

[0164] In some embodiments of the above formula, R 1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R 1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 It is an alkoxy, -CN, F, or Cl. In yet another embodiment, R 1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 In another embodiment, R 1f C 1~3 Alkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1f C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, R1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1f C 1~3 Alkyl, C 1~3 In another embodiment, R 1f C 1~3 Alkoxy, C 1~3 In yet another embodiment, R 1f C 1~3 Alkyl, C 1~3 It is a haloalkyl, F, or Cl.

[0165] In some embodiments of the above formula, R 1g C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is being replaced by an arbitrary choice.

[0166] In another embodiment, R 1g is, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2)0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, carbocyclyls, heterocyclyls, aryls, and heteroaryls are 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0167] In another embodiment, R 1g C 3~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0168] In another embodiment, R 1g C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6-5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R5 It is being replaced by an arbitrary choice.

[0169] In another embodiment, R 1g C 2~6 Alkyl, C 2~6 Alkinyl, C 2~6 Haloalkyl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0170] In some embodiments of the above formula, R 1g’ C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ) or -(CH2) 0~4 -C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is being replaced by an arbitrary choice.

[0171] In another embodiment, R 1g’ is, -(CH2) 0~6 -C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10-NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, heterocyclyls are 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0172] In another embodiment, R 1g’ C 3~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S.0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted, and heterocyclyls have 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0173] In another embodiment, R 1g’ C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2)0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted, and heterocyclyls have 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0174] In another embodiment, R 1g’ C 2~6 Alkyl, C 2~6 Alkinyl, C 2~6 Haloalkyl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2)0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted, and heterocyclyls have 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0175] In some embodiments of the above formula, R 1h C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is optionally replaced by R. In another embodiment, 1h is, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10(CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, carbocyclyls, heterocyclyls, aryls, and heteroaryls are 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0176] In another embodiment, R 1h C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2)0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0177] In another embodiment, R 1h C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4-NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0178] In some embodiments of the above formula, R 1h’ C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ) or -(CH2) 0~4 -C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is optionally replaced by R. In another embodiment, 1h’ is, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2)0~6 -5-7 member heterocycline, -C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, heterocyclyls are 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0179] In another embodiment, R 1h’ C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2)0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted, and heterocyclyls have 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0180] In another embodiment, R 1h’ C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4-C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted, and heterocyclyls have 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0181] In some embodiments of the above formula, R 1i H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is optionally replaced by R. In another embodiment, 1i is, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2)0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, carbocyclyls, heterocyclyls, aryls, and heteroaryls are 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0182] In another embodiment, R 1i C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0183] In another embodiment, R 1i H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0184] In some embodiments of the above formula, R1j C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0185] In another embodiment, R 1j H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, and alkynyl has 1 to 3 R 2 It is optionally replaced by R. In another embodiment, 1j is, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6-5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4-5 or 6-membered heteroaryls, carbocyclyls, heterocyclyls, aryls, and heteroaryls are 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0186] In another embodiment, R 1j H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0187] In some embodiments of the above formula, R on the benzoxazole ring 1d , R 1i and R 1j In another embodiment, R 1d and R 1i H is R 1j is not H. In another embodiment, R 1i and R 1j H is R 1d is not H. In another embodiment, R 1d and R 1j H is R 1i is not H. In another embodiment, R 1d H is R 1i and R1j is not H. In another embodiment, R 1i H is R 1d and R 1j is not H. In another embodiment, R 1j H is R 1d and R 1i It is not H.

[0188] In some embodiments of the above formula, each R 1k H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ) are selected from, and alkynyl has 1 to 3 R 2 It is optionally replaced by R. In another embodiment, each R 1k These are independently H, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -C(O)O(CH2) 0~4 -C 3~7 -C(O)O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~4 -5-7 member heterocycline, -C(O)O(CH2) 0~4 -C 6~10 -C(O)O(CH2) containing aryl or 1 to 3 heteroatoms selected from O, N, and S 0~4- Selected from 5- or 6-membered heteroaryls, carbocyclyl, heterocyclyl, aryl, and heteroaryl have 1 to 5 R 5 It is being replaced by an arbitrary choice.

[0189] In another embodiment, each R 1k Independently, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 ) Selected from 2, alkynyl has 1 to 3 R 2 It is optionally replaced by R. In yet another embodiment, each R 1k It is independently, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -C(O)O(CH2) 0~4 -C 3~7 -C(O)O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~4 -5-7 member heterocycline, -C(O)O(CH2) 0~4 -C 6~10 -C(O)O(CH2) containing aryl or 1 to 3 heteroatoms selected from O, N, and S 0~4 - Selected from 5- or 6-membered heteroaryls, carbocyclyl, heterocyclyl, aryl, and heteroaryl have 1 to 5 R 5It is being replaced by an arbitrary choice.

[0190] In some embodiments of the above formula, each R 2 These are independently NH2, -NH(C 1~4 Alkyl), -N(C 1~4 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~4 Alkyl), -C(O)N(C 1~4 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 In another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ) or -NHS(O)2R 9 In yet another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ) or -NR 9 S(O)2R 9 In another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R9 , -NHS(O)2R 9 or -NR 9 S(O)2R 9 In yet another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 In another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 In another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 That is the case.

[0191] In another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 In yet another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 In another embodiment, each R 2 These are independently NH2, -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 In yet another embodiment, each R 2 Independently, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 In another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 or -N(R 9 )C(O)(R 9 ) In yet another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHS(O)2R 9 or -NR 9 S(O)2R 9 In another embodiment, each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-C(O)NH2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 In yet another embodiment, each R 2 These are independently NH2, -C(O)NH2, and -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 That is the case.

[0192] In some embodiments of the above formula, R 3 is H or C 1~3 It is alkyl. In another embodiment, R 3 C 1~6 It is alkyl. In yet another embodiment, R 3 is H or C 2~6It is alkyl. In another embodiment, R 3 is H or C 3~6 It is alkyl. In yet another embodiment, R 3 is H, methyl, ethyl, n-propyl, or i-propyl. In another embodiment, R 3 is H, ethyl, n-propyl, or i-propyl. In yet another embodiment, R 3 is H, n-propyl or i-propyl. In another embodiment, R 3 is H, methyl, or ethyl. In yet another embodiment, R 3 is H or methyl. In another embodiment, R 3 H is H.

[0193] In some embodiments of the above formula, R 4 is H or C 1~3 It is alkyl. In another embodiment, R 4 C 1~6 It is alkyl. In yet another embodiment, R 4 is H or C 2~6 It is alkyl. In another embodiment, R 4 is H or C 3~6 It is alkyl. In yet another embodiment, R 4 is H, methyl, ethyl, n-propyl, or i-propyl. In another embodiment, R 4 is H, ethyl, n-propyl, or i-propyl. In yet another embodiment, R 4 is H, n-propyl or i-propyl. In another embodiment, R 4 is H, methyl, or ethyl. In yet another embodiment, R 4 is H or methyl. In another embodiment, R 4 H is H.

[0194] In some embodiments of the above formula, each R 5 Independently, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6Alkoxy, C 1~3 Haloalkyl, halogen, -OH, -C(O)H, -C(O)(C 1~6 Alkyl), -C(O)(C 6~10 aryl), -C(O)(5 or 6-membered heteroaryl), -C(O)(C 3~7 Carbocyclyl), -C(O)(5-7 member heterocyclyl), -(CH2) 0~3 C(O)OC 1~6 Alkyl, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-NHC(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -NHS(O)2R 9 , -NR 9 S(O)2R 9 , -S(O) q NHR 9 , -S(O) q N(R 9 )2, -S(O) q R 9 , C 1~6 Hydroxyalkyl, -O(CH2) 1~3 CN, -(CH2) 0~6 -C 3~7 Carbocyclyl, CN, -O(CH2) 0~3 (C6~C 10 -O(CH2) containing 1 to 3 heteroatoms selected from aryl, adamantyl, O, N, and S 0~3 -5 or 6-membered heteroaryl, containing 1 to 3 heteroatoms selected from O, N, and S -(CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 -C 6~10 -(CH2) containing an aryl group and 1 to 3 heteroatoms selected from O, N, and S. 0~6 -5 or 6-membered heteroaryl, alkyl is 1-3 R6 It is optionally substituted, and carbocyclyl, heterocyclyl, aryl and heteroaryl have 1 to 4 R 8 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7 It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S; or 2 R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7 Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is either optionally replaced by; or two R 5 If they are on the same atom, they form (O).

[0195] In another embodiment, each R 5 Independently, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkyl, halogen, -OH, -C(O)H, -C(O)(C 1~6 Alkyl), -C(O)(C 6~10 aryl), -C(O)(5 or 6-membered heteroaryl), -C(O)(C 3~7 Carbocyclyl), -C(O)(5-7 member heterocyclyl)-(CH2) 0~3 C(O)OC 1~6 Alkyl, -C(O)NH2, -C(O)NH(C1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-NHC(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -NHS(O)2R 9 , -NR 9 S(O)2R 9 , -S(O) q NHR 9 , -S(O) q N(R 9 )2, -S(O) q R 9 , C 1~6 Hydroxyalkyl, -O(CH2) 1~3 CN, CN, -O(CH2) 0~6 -C 3~7 -O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~6 -5-7 member heterocycline, -O(CH2) 0~3 (C6~C 10 -O(CH2) containing 1 to 3 heteroatoms selected from aryl, adamantyl, O, N, and S 0~3 -5 or 6-membered heteroaryl, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 -C 6~10 -(CH2) containing an aryl group and 1 to 3 heteroatoms selected from O, N, and S. 0~6 -5 or 6-membered heteroaryl, alkyl is 1-3 R 6 It is optionally substituted, and carbocyclyl, heterocyclyl, aryl and heteroaryl have 1 to 4 R 8 It is either optionally replaced by; or two R 5If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7 It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S; or 2 R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7 Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is either optionally replaced by; or two R 5 If they are on the same atom, they form (O).

[0196] In another embodiment, each R 5 Independently, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkyl, halogen, -OH, -C(O)H, -C(O)(C 1~6 Alkyl), -C(O)(C 6~10 aryl), -C(O)(5 or 6-membered heteroaryl), -C(O)(C 3~7 Carbocyclyl), -C(O)(5-7 member heterocyclyl)-(CH2) 0~3 C(O)OC 1~6 Alkyl, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9), -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-NHC(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -NHS(O)2R 9 , -NR 9 S(O)2R 9 , -S(O) q NHR 9 , -S(O) q N(R 9 )2, -S(O) q R 9 , C 1~6 Hydroxyalkyl, -O(CH2) 1~3 CN, CN, -O(CH2) 0~6 -C 3~7 -O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~6 -5-7 member heterocycline, -O(CH2) 0~3 (C6~C 10 -O(CH2) containing 1 to 3 heteroatoms selected from aryl, adamantyl, O, N, and S 0~3 -5 or 6-membered heteroaryl, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 -C 6~10 -(CH2) containing an aryl group and 1 to 3 heteroatoms selected from O, N, and S. 0~6 -5 or 6-membered heteroaryl, alkyl is 1-3 R 6 It is optionally substituted, and carbocyclyl, heterocyclyl, aryl and heteroaryl have 1 to 4 R 8 It is being replaced by an arbitrary choice.

[0197] In another embodiment, two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S; or 2 R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7 Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is either optionally replaced by; or two R 5 If they are on the same atom, they form (O).

[0198] In another embodiment, two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7 It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is optionally replaced by. In yet another embodiment, two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7 Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is optionally replaced by. In yet another embodiment, two R 5If they are on the same atom, they form (O).

[0199] In another embodiment, each R 5 Independently, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkyl, halogen, -OH, -C(O)H, -C(O)(C 1~6 Alkyl), -C(O)(C 6~10 aryl), -C(O)(5 or 6-membered heteroaryl), -C(O)(C 3~7 Carbocyclyl), -C(O)(5-7 member heterocyclyl)-(CH2) 0~3 C(O)OC 1~6 Alkyl, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-NHC(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -NHS(O)2R 9 , -NR 9 S(O)2R 9 , -S(O) q NHR 9 , -S(O) q N(R 9 )2, -S(O) q R 9 , C 1~6 Hydroxyalkyl, -O(CH2) 1~3 CN is an alkyl group, and alkyl groups have 1 to 3 R 6 It is optionally substituted, and carbocyclyl, heterocyclyl, aryl and heteroaryl have 1 to 4 R 8 It is either optionally replaced by; or two R 5If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7 It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S; or 2 R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7 Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is either optionally replaced by; or two R 5 If they are on the same atom, they form (O).

[0200] In another embodiment, each R 5 Independently, -O(CH2) 0~6 -C 3~7 -O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~6 -5-7 member heterocycline, -O(CH2) 0~3 (C6~C 10 -O(CH2) containing 1 to 3 heteroatoms selected from aryl, adamantyl, O, N, and S 0~3 -5 or 6-membered heteroaryl, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 -C 6~10 -(CH2) containing an aryl group and 1 to 3 heteroatoms selected from O, N, and S. 0~6-5 or 6-membered heteroaryls, carbocyclyls, heterocyclyls, aryls, and heteroaryls are 1 to 4 R 8 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7 It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S; or 2 R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7 Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is either optionally replaced by; or two R 5 If they are on the same atom, they form (O).

[0201] In some embodiments of the above formula, R 6 -NH2, -NH(C 1~4 Alkyl), -N(C 1~4 Alkyl)2, C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 7 It is optionally replaced by R. In another embodiment, 6 -NH2, -NH(C 1~6 Alkyl) or -N(C 1~6 Alkyl)2. In another embodiment, R 6 C 6~10A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 7 It is optionally replaced by R. In yet another embodiment, 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 A 5 or 6-membered heteroaryl compound containing alkyl)2phenyl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl compounds contain 1 to 3 R 7 It is optionally replaced by R. In another embodiment, 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, C 6~10 A 5-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein aryl and heteroaryl contain 1 to 3 R 7 It is optionally replaced by R. In yet another embodiment, 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, C 6~10 A 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein aryl and heteroaryl contain 1 to 3 R 7 It is optionally replaced by R. In another embodiment, 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 A 5-membered heteroaryl compound containing 1 to 3 heteroatoms selected from alkyl, phenyl, or O, N, and S, wherein phenyl and heteroaryl compounds contain 1 to 3 R 7 It is being replaced by an arbitrary choice.

[0202] In another embodiment, R 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6A six-membered heteroaryl compound containing 1 to 3 heteroatoms selected from alkyl, phenyl, or O, N, and S, wherein phenyl and heteroaryl compounds contain 1 to 3 R 7 It is optionally replaced by R. In yet another embodiment, 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl) 2 or 1-3 R 7 C is optionally replaced by 6~10 It is an arrow. In another embodiment, R 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl) 2 or 1-3 R 7 It is a 5 or 6-membered heteroaryl compound containing 1 to 3 heteroatoms selected from O, N, and S, which are optionally substituted. In another embodiment, R 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl) 2 or 1-3 R 7 It is a phenyl that is optionally substituted with R. In yet another embodiment, R 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl) 2, 1-3 R 7 It is a 5-membered heteroaryl that is optionally substituted with R. In another embodiment, R 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl) 2, 1-3 R 7 It is a 6-membered heteroaryl that is optionally substituted.

[0203] In some embodiments of the above formula, each R 7 Independently, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy, C 1~4 Haloalkoxy, halogen, or C 6~10 It is an arrow. In another embodiment, each R 7 Independently, C1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 In yet another embodiment, each R is a haloalkoxy, halogen, or phenyl. 7 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 In another embodiment, each R 7 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy or C 6~10 It is an aryl. In yet another embodiment, each R 7 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkyl, halogen, or C 6~10 It is an arrow. In another embodiment, each R 7 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~3 Haloalkoxy, halogen, or C 6~10 It is an aryl. In yet another embodiment, each R 7 Independently, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, or C 6~10 It is an arrow. In another embodiment, each R 7 Independently, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, or C 6~10 It is an aryl. In yet another embodiment, each R 7 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, or C 6~10 It is an arrow. In another embodiment, each R 7Independently, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, or C 6~10 It is an aryl. In yet another embodiment, each R 7 Independently, C 1~6 Alkyl, C 1~6 Alkyl, halogen, or C 6~10 It is an arrow. In another embodiment, each R 7 Independently, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~3 or C 6~10 It is an aryl. In yet another embodiment, each R 7 Independently, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy, C 1~4 These are haloalkoxys, halogens, or phenyls.

[0204] In some embodiments of the above formula, each R 8 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 In another embodiment, each R is a haloalkoxy, halogen, or -OH. 8 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 In yet another embodiment, each R 8 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 In another embodiment, each R is a haloalkoxy or -OH. 8 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 It is an alkoxy, halogen, or -OH. In yet another embodiment, each R 8Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 In another embodiment, each R is a haloalkoxy, halogen, or -OH. 8 Independently, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 In yet another embodiment, each R is a haloalkoxy, halogen, or -OH. 8 Independently, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 In another embodiment, each R is a haloalkoxy, halogen, or -OH. 8 Independently, C 1~6 Alkyl, C 1~6 In yet another embodiment, each R is a haloalkyl, halogen, or -OH. 8 Independently, C 1~6 Alkoxy, C 1~6 In another embodiment, each R is a haloalkoxy, halogen, or -OH. 8 Independently, C 1~6 Alkyl, C 1~6 It is an alkoxy, halogen, or -OH. In yet another embodiment, each R 8 These are independently halogens or -OH. In another embodiment, each R 8 Independently, C 1~6 Alkyl, C 1~6 It is a haloalkyl or halogen.

[0205] In some embodiments of the above formula, R 9 C 1~4 Alkyl, C 1~4 Haloalkyl, 5-7 membered heterocycline containing 1-3 heteroatoms selected from O, N, and S, C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 11 It is optionally replaced by R. In another embodiment, 9 C1~6 Alkyl, C 1~6 A 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from haloalkyl, O, N, and S, phenyl, or a 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, wherein phenyl and heteroaryl contain 1-3 R 11 It is optionally replaced by R. In another embodiment, 9 C 1~6 Alkyl or C 1~6 In yet another embodiment, R 9 C is a 5-7 membered heterocycline containing 1-3 heteroatoms selected from O, N, and S. 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 11 It is optionally replaced by R. In another embodiment, 9 C 1~6 Alkyl, C 1~6 Haloalkyl, C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 11 It is optionally replaced by R. In yet another embodiment, 9 C 1~6 Alkyl, C 1~6 A 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from haloalkyl, O, N, and S, or a 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, wherein the heteroaryl contains 1-3 R 11 It is optionally replaced by R. In another embodiment, 9 C 1~6 Alkyl, C 1~6 A 5-7 membered heterocyclyl or -5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from haloalkyl, O, N, and S, wherein the heteroaryl contains 1-3 R 11 It is being replaced by an arbitrary choice.

[0206] In another embodiment, R 9 C 1~6 Alkyl, C 1~6 A 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from haloalkyl, O, N, and S, phenyl, or a 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, wherein phenyl and heteroaryl contain 1-3 R 11 It is optionally replaced by R. In yet another embodiment, 9 C 1~6 Alkyl, C 1~6 Haloalkyl, 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, phenyl, or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, where aryl and heteroaryl contain 1-3 R 11 It is optionally replaced by R. In another embodiment, 9 C 1~6 Alkyl, C 1~6 A 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from haloalkyl, O, N, and S, phenyl, or a 5 membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, wherein phenyl and heteroaryl contain 1-3 R 11 It is optionally replaced by R. In yet another embodiment, 9 C 1~6 Alkyl, C 1~6 A 5 or 6-membered heterocycline containing 1 to 3 heteroatoms selected from haloalkyl, O, N, and S, phenyl, or a 5 or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, wherein phenyl and heteroaryl contain 1 to 3 R 11 It is optionally replaced by R. In another embodiment, 9 C 1~6 Alkyl, C 1~6 A 6 or 7-membered heterocyclyl containing 1 to 3 heteroatoms selected from haloalkyl, O, N, and S, phenyl, or a 5 or 6-membered heteroaryl containing 1 to 3 heteroatoms selected from O, N, and S, wherein phenyl and heteroaryl contain 1 to 3 R 11It is optionally replaced by R. In yet another embodiment, 9 C 1~6 Alkyl, C 1~6 A 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from haloalkyl, O, N, and S, phenyl, or a 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1-3 R 11 It is optionally replaced by R. In another embodiment, 9 C 1~6 Alkyl, C 1~6 It is a 5-7 membered heterocycline containing a haloalkyl or 1-3 heteroatoms selected from O, N, and S. In yet another embodiment, R 9 C 1~6 Alkyl, C 1~6 Haloalkyl or 1-3 R 11 It is a phenyl that is optionally substituted with R. In another embodiment, R 9 C 1~6 Alkyl, C 1~6 A 5- or 6-membered heteroaryl containing a haloalkyl or 1 to 3 heteroatoms selected from O, N, and S, wherein the heteroaryl has 1 to 3 R 11 It is being replaced by an arbitrary choice.

[0207] In some embodiments of the above formula, each R 10 C 1~6 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy, C 1~4 It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3In yet another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy or C 1~6 It is a haloalkoxy; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Form a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 It forms a 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S.

[0208] In another embodiment, each R 10 C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Form a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 10 C1~6 Alkyl, C 1~6 It is a haloalkyl or halogen; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 10 C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Form a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or two R 10 When present on adjacent atoms, they form a 5- or 6-membered heteroaryl aryl ion containing phenyl or 1 to 3 heteroatoms selected from O, N, and S, together with the atom to which they are attached.

[0209] In another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 A five-membered heteroaryl is formed, comprising aryl or 1 to 3 heteroatoms selected from O, N, and S. In yet another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, they form a five-membered heteroaryl ion containing phenyl or 1 to 3 heteroatoms selected from O, N, and S, together with the atom to which they are attached. In another embodiment, each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or two R 10 If they are on adjacent atoms, they form a six-membered heteroaryl ion containing phenyl or 1 to 3 heteroatoms selected from O, N, and S, together with the atom to which they are attached. In yet another embodiment, two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, two R 10 If they are on adjacent atoms, they form a 5 or 6-membered heteroaryl aryl ion containing phenyl or 1 to 3 heteroatoms selected from O, N, and S, together with the atom to which they are attached. In yet another embodiment, two R 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Form an aryl. In another embodiment, two R 10When present on adjacent atoms, they form a 5- or 6-membered heteroaryl aryl ion containing 1 to 3 heteroatoms selected from O, N, and S, together with the atom to which they are attached.

[0210] In some embodiments of the above formula, each R 11 Independently, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by R. In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by R. In yet another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by R. In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -N(C) 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is being replaced by an arbitrary choice.

[0211] In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, -NHC(O)(C 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by R. In yet another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by R. In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is being replaced by an arbitrary choice.

[0212] In another embodiment, each R 11 Independently, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12It is optionally replaced by R. In yet another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by R. In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is being replaced by an arbitrary choice.

[0213] In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6It is alkyl or halogen. In yet another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 It is a haloalkoxy or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by R. In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, -NHC(O)(C 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by R. In yet another embodiment, each R 11 Independently, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is being replaced by an arbitrary choice.

[0214] In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 When present on adjacent atoms, they form a 5- or 6-membered heteroaryl phenyl or heteroaryl phenyl and heteroaryl phenyl and heteroaryl phenyl 12 It is optionally replaced by R. In yet another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11 When present on adjacent atoms, they form a five-membered heteroaryl ion containing phenyl or 1 to 3 heteroatoms selected from O, N, and S, together with the atom to which they are attached, and phenyl and heteroaryl ions contain 1 to 3 R 12 It is optionally replaced by R. In another embodiment, each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~4 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 Alkyl) or halogen; or two R 11When present on adjacent atoms, they form a six-membered heteroaryl ion containing phenyl or 1 to 3 heteroatoms selected from O, N, and S, together with the atom to which they are attached, and phenyl and heteroaryl ions contain 1 to 3 R 12 It is optionally replaced by. In yet another embodiment, two R 11 When present on adjacent atoms, they form a 5- or 6-membered heteroaryl phenyl or heteroaryl phenyl and heteroaryl phenyl and heteroaryl phenyl 12 It is optionally replaced by. In another embodiment, two R 11 If they are on adjacent atoms, they form 1 to 3 R atoms together with the atom they are attached to. 12 In another embodiment, two R 11 If they are on adjacent atoms, they contain 1 to 3 heteroatoms selected from O, N, and S, together with the atom to which they are attached, and 1 to 3 R 12 It forms a 5- or 6-membered heteroaryl that is optionally substituted.

[0215] In some embodiments of the above formula, each R 12 Independently, C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy or C 1~3 In another embodiment, each R 12 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl or C 1~6 It is an alkoxy. In yet another embodiment, each R 12 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl or C 1~3 In another embodiment, each R 12 Independently, C 1~6 Alkyl, C 1~6 Alkoxy or C 1~3In yet another embodiment, each R 12 Independently, C 1~6 Haloalkyl, C 1~6 Alkoxy or C 1~3 In another embodiment, each R 12 Independently, C 1~6 Alkyl or C 1~6 In yet another embodiment, each R 12 Independently, C 1~6 Alkyl or C 1~6 It is an alkoxy. In another embodiment, each R 12 Independently, C 1~6 Alkyl or C 1~3 In yet another embodiment, each R 12 Independently, C 1~6 Haloalkyl or C 1~6 It is an alkoxy. In another embodiment, each R 12 Independently, C 1~6 Haloalkyl or C 1~3 In yet another embodiment, each R 12 Independently, C 1~6 Alkoxy or C 1~3 In another embodiment, each R 12 Independently, C 1~6 It is alkyl. In yet another embodiment, each R 12 Independently, C 1~6 In another embodiment, each R 12 Independently, C 1~3 In yet another embodiment, each R 12 Independently, C 1~6 It is an alkoxy.

[0216] In some embodiments of the above formula, R 13 Each of these occurrences is independent of C 1~4 Alkyl, C 1~4 Haloalkyl, C 6~10A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the alkyl has 1 to 2 C 1~6 They are optionally substituted with alkoxys, and aryls and heteroaryls have 1 to 3 R 14 It is optionally replaced by R. In another embodiment, 13 Each of these occurrences is independent of C 1~6 Alkyl or C 1~6 It is a haloalkyl, where alkyl is composed of 1-2 carbon atoms. 1~6 It is optionally substituted with an alkoxy. In yet another embodiment, R 13 Each of these occurrences is independent of C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 14 It is optionally replaced by R. In another embodiment, 13 Each of these occurrences is independent of C 1~6 Alkyl, C 1~6 A 5- or 6-membered heteroaryl compound containing one to three heteroatoms selected from haloalkyl, phenyl, or O, N, and S, wherein the alkyl has one to two carbon atoms. 1~6 They are optionally substituted with alkoxys, and phenyl and heteroaryl groups have 1 to 3 R groups. 14 It is optionally replaced by R. In yet another embodiment, 13 Each of these occurrences is independent of C 1~6 Alkyl, C 6~10 A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the alkyl has 1 to 2 C 1~6 They are optionally substituted with alkoxys, and aryls and heteroaryls have 1 to 3 R 14 It is being replaced by an arbitrary choice.

[0217] In another embodiment, R 13 Each of these occurrences is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 6~10A 5-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the alkyl has 1 to 2 C 1~6 They are optionally substituted with alkoxys, and aryls and heteroaryls have 1 to 3 R 14 It is optionally replaced by R. In yet another embodiment, 13 Each of these occurrences is independent of C 1~6 Alkyl, C 1~6 A five-membered heteroaryl compound containing one to three heteroatoms selected from haloalkyl, phenyl, or O, N, and S, wherein the alkyl has one to two C atoms. 1~6 They are optionally substituted with alkoxys, and phenyl and heteroaryl groups have 1 to 3 R groups. 14 It is optionally replaced by R. In another embodiment, 13 Each of these occurrences is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 6~10 A 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S, where alkyl contains 1 to 2 C 1~6 They are optionally substituted with alkoxys, and aryls and heteroaryls have 1 to 3 R 14 It is optionally replaced by R. In yet another embodiment, 13 Each of these occurrences is independent of C 1~6 Alkyl, C 1~6 A six-membered heteroaryl compound containing one to three heteroatoms selected from haloalkyl, phenyl, or O, N, and S, wherein the alkyl has one to two C atoms. 1~6 They are optionally substituted with alkoxys, and phenyl and heteroaryl groups have 1 to 3 R groups. 14 It is being replaced by an arbitrary choice.

[0218] In some embodiments of the above formula, each R 14 Independently, C 1~4 Alkyl, C 1~4 Haloalkyl, C 1~4 Alkoxy, C 1~4 Haloalkoxy, halogen, C 6~10It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 In another embodiment, each R 14 -C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 A 5 or 6-membered heteroaryl comprising a haloalkoxy, halogen, phenyl, or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Halogen, C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~3 Haloalkoxy, halogen, C 6~10 It is a 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S.

[0219] In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, halogen, C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Alkyl, halogen, C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Haloalkyl, C 1~3 Haloalkoxy, halogen, C 6~10 It is a 5 or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C1~6 Alkoxy, C 1~3 It is a six-membered heteroaryl containing one to three heteroatoms selected from haloalkoxy, halogen, phenyl, or O, N, and S. In another embodiment, each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 It is a six-membered heteroaryl compound containing one to three heteroatoms selected from haloalkoxy, halogen, phenyl, or O, N, and S.

[0220] In some embodiments of the above formula, R 15 is H or C 1~3 It is alkyl. In another embodiment, R 15 C 1~6 It is alkyl. In yet another embodiment, R 15 is H or C 2~6 It is alkyl. In another embodiment, R 15 is H or C 3~6 It is alkyl. In yet another embodiment, R 15 is H, methyl, ethyl, n-propyl, or i-propyl. In another embodiment, R 15 is H, ethyl, n-propyl, or i-propyl. In yet another embodiment, R 15 is H, n-propyl or i-propyl. In another embodiment, R 15 is H, methyl, or ethyl. In yet another embodiment, R 15 is H or methyl. In another embodiment, R 15 H is H.

[0221] In some embodiments of the above formula, q is 0 or 1. In other embodiments, q is 1 or 2. In other embodiments, q is 0 or 2. In other embodiments, q is 0. In other embodiments, q is 1. In other embodiments, q is 2.

[0222] In some embodiments of the above formula, R d1 H is H.

[0223] In some embodiments of the above formula, R d1 H is R d2 H is H.

[0224] In some embodiments of the above formula, R d1 H is, [ka] It is a double bond.

[0225] In some embodiments of the above formula, R d1 H is, [ka] It is a single bond.

[0226] In some embodiments of the above formula, R d2 H is, [ka] It is a double bond.

[0227] In some embodiments of the above formula, R d2 H is, [ka] It is a single bond.

[0228] In some embodiments of the above formula, R d1 H is R d2 H is, [ka] It is a double bond.

[0229] In some embodiments of the above formula, Rd1 H is R d2 H is, [ka] It is a single bond.

[0230] In one embodiment, the compounds disclosed herein, for example, compounds of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18, can be used as targeted ligase binders for preparing bifunctional decomposition agents. In one embodiment, the bifunctional decomposition agent is of formula (A): [ka] It is a compound of the formula, in which, A target ligand is a group that can bind to a target protein, for example, the target proteins disclosed in Table 1 herein; A linker is either absent or a group that covalently binds the target ligand to the targeting ligase binder; A targeted ligase binder is a group that can bind to a ligase (e.g., cereblon E3 ubiquitin ligase), and the targeted ligase binder is represented by formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu) These are compounds of (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18, or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers.

[0231] Linkers and target ligands and examples of their synthesis are provided in the related U.S. Provisional Patent Application No. 62 / 901,161, entitled "BIFUNCTIONAL DEGRADERS AND THEIR METHODS OF USE" (Novartis reference number PAT058639-US-PSP), filed on September 16, 2019, which is incorporated herein by reference in its entirety.

[0232] Embodiment 1: A compound that can bind to the cereblon complex and alter its specificity to induce ubiquitination and degradation of complex-related proteins, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0233] Embodiment 2: The compound of Embodiment 1, comprising (i) a tris-tryptophan pocket binding moiety that binds to the tris-tryptophan pocket of cereblon E3 ligase; and (ii) a target affinity moiety covalently bonded to the tris-tryptophan pocket binding moiety that interacts with the surface of cereblon E3 ligase, alters its surface, and causes the ligase to have affinity for a target protein.

[0234] Embodiment 3: Formula (I): [ka] (In the formula, [ka] It is optionally a double bond; R d1 H, -CH2OC(O)R 15 -CH2OP(O)OHOR 15 or -CH2OP(O)(R 15 )2; R d2 H, C 1~6 Alkyl, halogen, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl; R d3 teeth, [ka] [ka] and; A 1 This is a 5- or 6-membered heterocycline or NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 3 R 1d It is a 5-membered heteroaryl substituted with; A 2 C 5~7 Carbocyclyl or N, NR 1k , a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O and S, and carbocykrill and heterocyclyl contain 1-3 R 1d It has been replaced with; X 1 , NR 4 or S; X 2 and X 2a Each of them operates independently, CR1a or N; Each X 3 CR is independent. 1d or N; two or fewer X 3 is N; Each X 4 CR is independent. 1d or N, and at least one X 4 is N, and there are two or fewer X 4 is N; Each X 5 CR is independent. 1a or N; two or fewer X 5 is N; X 6 , NR 1k , O or S; X 7 , NR 4 , O or S; R 1a and R 1b These are H and C, respectively, independently. 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl; R 1c C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2)0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4-5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; Each R 1d H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 It is a haloalkoxy, -CN, F, or Cl; R 1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 It is a haloalkoxy, -CN, F, or Cl; R 1g C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1h C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1i H, C 1~6 Alkyl, C 2~6Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2-(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S.0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1j H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R on the benzoxazole ring 1d , R 1iand R 1j It is not possible for all of them to be H at the same time; Each R 1k H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -C(O)O(CH2) 0~4 -C 3~7 -C(O)O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~4 -5-7 member heterocycline, -C(O)O(CH2) 0~4 -C 6~10 -C(O)O(CH2) containing aryl or 1 to 3 heteroatoms selected from O, N, and S 0~4 - Selected from 5- or 6-membered heteroaryls, the alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; Each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 and; R 3 is H or C 1~6 It is alkyl; R 4 is H or C 1~6 It is alkyl; Each R 5 Independently, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkyl, halogen, -OH, -C(O)H, -C(O)(C 1~6 Alkyl), -C(O)(C 6~10 aryl), -C(O)(5 or 6-membered heteroaryl), -C(O)(C 3~7 Carbocyclyl), -C(O)(5-7 member heterocyclyl)-(CH2) 0~3 C(O)OC 1~6 Alkyl, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-NHC(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -NHS(O)2R 9 , -NR 9 S(O)2R 9 , -S(O) q NHR 9 , -S(O) q N(R 9 )2, -S(O)q R 9 , C 1~6 Hydroxyalkyl, -O(CH2) 1~3 CN, CN, -O(CH2) 0~6 -C 3~7 -O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~6 -5-7 member heterocycline, -O(CH2) 0~3 (C6~C 10 -O(CH2) containing 1 to 3 heteroatoms selected from aryl, adamantyl, O, N, and S 0~3 -5 or 6-membered heteroaryl, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 -C 6~10 -(CH2) containing an aryl group and 1 to 3 heteroatoms selected from O, N, and S. 0~6 -5 or 6-membered heteroaryl, alkyl is 1-3 R 6 It is optionally substituted, and carbocyclyl, heterocyclyl, aryl and heteroaryl have 1 to 4 R 8 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7 It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S; or 2 R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is either optionally replaced by; or two R 5 If they are on the same atom, they form (O); R 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 7 It is optionally replaced by; Each R 7 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, or C 6~10 It is an allele; Each R 8 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy, halogen, or -OH; R 9 C 1~6 Alkyl, C 1~6 Haloalkyl, 5-7 membered heterocycline containing 1-3 heteroatoms selected from O, N, and S, C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 11 It is optionally replaced by; Each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or Two R's 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S; Each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NHC(O)(C) 1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 It is alkyl or halogen; or Two R's 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by; Each R 12 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy or C 1~3 It is a haloalkoxy; R 13 Each of these occurrences is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 6~10 A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the alkyl has 1 to 2 C 1~6 They are optionally substituted with alkoxys, and aryls and heteroaryls have 1 to 3 R 14 It is optionally replaced by; Each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, C6~10 A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S; R 15 is H or C 1~6 It is alkyl; and (q is 0, 1, or 2) A compound of Embodiment 1 or 2 having, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0235] Embodiment 4: R d1 The compound of Embodiment 3, wherein H is present.

[0236] Embodiment 5: R d1 is -CH2OC(O)R 15 -CH2OP(O)OHOR 15 or -CH2OP(O)(R 15 The compound of Embodiment 3, which is 2.

[0237] Embodiment 6: R d2 The compound is one of the compounds from Embodiments 1 to 5, wherein H is present.

[0238] Embodiment 7: R d1 and R d2 Each of these is independently a compound from any one of Embodiments 1 to 6, wherein each is H.

[0239] Embodiment 8: R 1d The compound is one of the compounds from Embodiments 1 to 7, wherein H is present.

[0240] Embodiment 9: R d3 teeth, [ka] [ka] [ka] [ka] [ka] A compound which is any one of embodiments 1 to 8.

[0241] Embodiment 10:R d3 teeth, [ka] [ka] [ka] A compound which is any one of embodiments 1 to 9.

[0242] Embodiment 11: [ka] [ka] A compound from any one of Embodiments 1 to 10, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, having a formula selected from the above.

[0243] Embodiment 12: 1-(benzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-ethinylbenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-methylbenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-iodobenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-iodobenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; Phenyl(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-5-yl)carbamate; 1-(6-chloropyrazolo[1,5-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-(1-benzyl-1,2,3,6-tetrahydropyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-(1-(4-(tert-butyl)benzoyl)-1,2,3,6-tetrahydropyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; and 1-(6-(1-benzylpiperidine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione A compound selected from any one of Embodiments 1 to 11, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0244] Embodiment 13: A pharmaceutical composition comprising one of the compounds from Embodiments 1 to 12 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

[0245] Embodiment 14: The pharmaceutical composition of Embodiment 13, further comprising at least one additional pharmaceutical product.

[0246] Embodiment 15: A pharmaceutical composition of Embodiment 13 or Embodiment 14 for use in the treatment or prevention of disorders, diseases, or conditions mediated by cereblon.

[0247] Embodiment 16: A pharmaceutical composition of Embodiment 13 or Embodiment 14 for use in the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, and infectious diseases or disorders.

[0248] Embodiment 17: A method for preparing cereblon in a biological sample, comprising contacting the sample with any one of the compounds from Embodiments 1 to 12 or a pharmaceutically acceptable salt thereof.

[0249] Embodiment 18: A method for inducing ubiquitination and degradation of a complex-related protein selected from the group listed in Table 1 in a biological sample by binding to and altering the specificity of a cereblon complex, comprising contacting the sample with any one of the compounds from Embodiments 1 to 12 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0250] Embodiment 19: A method for treating or preventing a cereblon-mediated disorder, disease, or condition in a subject, comprising administering one of the compounds from Embodiments 1 to 12 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0251] Embodiment 20: The method of Embodiment 19, wherein the disorder, disease, or condition is a respiratory disorder, proliferative disorder, autoimmune disorder, autoinflammatory disorder, inflammatory disorder, neurological disorder, or infectious disease or disorder.

[0252] Embodiment 21: The method of Embodiment 20, wherein the disorder, disease, or condition is a proliferative disorder.

[0253] Embodiment 22: The method of Embodiment 21, wherein the proliferative disorder is cancer.

[0254] Embodiment 23: The method of Embodiment 20, wherein the disorder, disease, or condition is a neurological disorder.

[0255] Embodiment 24: A method for treating or preventing a respiratory disorder, proliferative disorder, autoimmune disorder, autoinflammatory disorder, inflammatory disorder, neurological disorder, or infectious disease or disorder in a subject requiring such treatment, comprising administering a therapeutically effective amount of one compound from Embodiments 1 to 12 or a pharmaceutically acceptable salt thereof to the subject.

[0256] Embodiment 25: The method of Embodiment 24, wherein the disorder or disease is a proliferative disorder.

[0257] Embodiment 26: The method of Embodiment 25, wherein the proliferative disorder is cancer.

[0258] Embodiment 27: The method of Embodiment 24, wherein the disorder or disease is a neurological disorder.

[0259] Embodiment 28: Use of any one compound from Embodiments 1 to 12 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the preparation of a pharmaceutical for the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, or infectious diseases or disorders in subjects requiring such treatment or prevention.

[0260] Embodiment 29: Use of the compounds of Embodiments 1 to 12 or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers for the treatment or prevention of cancer.

[0261] Embodiment 30: A method for degrading a target protein in a biological sample, comprising contacting one of the compounds from Embodiments 1 to 12 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the target protein is selected from the group listed in Table 1.

[0262] Embodiment 31: A method for treating or preventing a target protein-mediated disorder, disease, or condition in a subject, comprising administering one of the compounds from Embodiments 1 to 12 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0263] Embodiment 32: The method of Embodiment 31, wherein the disorder, disease, or condition is a proliferative disorder.

[0264] Embodiment 33: The method of Embodiment 32, wherein the proliferative disorder is cancer.

[0265] Embodiment 34: The method of Embodiment 31, wherein the disorder, disease, or condition is a neurological disorder.

[0266] Embodiment 35: A compound selected from the following.

[0267] [Table 1]

[0268] [Table 2]

[0269] Embodiment 35A: A compound selected from the following, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0270] [Table 3]

[0271] [Table 4]

[0272] [Table 5]

[0273] [Table 6]

[0274] Embodiment 36: A pharmaceutical composition comprising a compound of Embodiment 35 or Embodiment 35A, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

[0275] Embodiment 37: The pharmaceutical composition of Embodiment 36, further comprising at least one additional pharmaceutical product.

[0276] Embodiment 38: A pharmaceutical composition of Embodiment 36 or Embodiment 37 for use in the treatment or prevention of disorders, diseases, or conditions mediated by cereblon.

[0277] Embodiment 39: A pharmaceutical composition of Embodiment 36 or Embodiment 37 for use in the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, or infectious diseases or disorders.

[0278] Embodiment 40: A method for inhibiting cereblon in a biological sample, comprising contacting the sample with a compound of Embodiment 35 or Embodiment 35A or a pharmaceutically acceptable salt thereof.

[0279] Embodiment 41: A method for inducing ubiquitination and degradation of a complex-related protein selected from the group listed in Table 1 in a biological sample by binding to and altering the specificity of a cereblon complex, comprising contacting the sample with a compound of Embodiment 35 or Embodiment 35A or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0280] Embodiment 42: A method for treating or preventing a cereblon-mediated disorder, disease, or condition in a subject, comprising administering a compound of Embodiment 35 or Embodiment 35A or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0281] Embodiment 43: The method of Embodiment 42, wherein the disorder, disease, or condition is a respiratory disorder, proliferative disorder, autoimmune disorder, autoinflammatory disorder, inflammatory disorder, neurological disorder, or infectious disease or disorder.

[0282] Embodiment 44: The method of Embodiment 43, wherein the disorder, disease, or condition is a proliferative disorder.

[0283] Embodiment 45: The method of Embodiment 44, wherein the proliferative disorder is cancer.

[0284] Embodiment 46: The method of Embodiment 43, wherein the disorder, disease, or condition is a neurological disorder.

[0285] Embodiment 47: A method for treating or preventing a respiratory disorder, proliferative disorder, autoimmune disorder, autoinflammatory disorder, inflammatory disorder, neurological disorder, or infectious disease or disorder in a subject in need thereof, comprising administering a therapeutically effective amount of the compound of Embodiment 35 or Embodiment 35A or a pharmaceutically acceptable salt thereof to the subject.

[0286] Embodiment 48: The method of Embodiment 47, wherein the disorder or disease is a proliferative disorder.

[0287] Embodiment 49: The method of Embodiment 48, wherein the proliferative disorder is cancer.

[0288] Embodiment 50: The method of Embodiment 47, wherein the disorder or disease is a neurological disorder.

[0289] Embodiment 51: Use of the compounds of Embodiment 35 or Embodiment 35A or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers in the preparation of a pharmaceutical for the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, or infectious diseases or disorders in subjects requiring such treatment or prevention.

[0290] Embodiment 52: Use of the compounds of Embodiment 35 or Embodiment 35A or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers for the treatment or prevention of cancer.

[0291] Embodiment 53: A method for degrading a target protein in a biological sample, comprising contacting the compound of Embodiment 35 or Embodiment 35A or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the target protein is selected from the group listed in Table 1.

[0292] Embodiment 54: A method for treating or preventing a target protein-mediated disorder, disease, or condition in a subject, comprising administering a compound of Embodiment 35 or Embodiment 35A or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0293] Embodiment 55: The method of Embodiment 54, wherein the disorder, disease, or condition is a proliferative disorder.

[0294] Embodiment 56: The method of Embodiment 55, wherein the proliferative disorder is cancer.

[0295] Embodiment 57: The method of Embodiment 54, wherein the disorder, disease, or condition is a neurological disorder.

[0296] Embodiment 58: A method for treating or preventing cancer in a subject, comprising administering a compound of Embodiment 35 or Embodiment 35A or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0297] Embodiment 59: Any one compound from Embodiments 1 to 12 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders or infectious diseases or disorders in subjects requiring such treatment or prevention.

[0298] Embodiment 60: Compounds of Embodiments 1 to 12 or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers thereof for use in the treatment or prevention of cancer.

[0299] Embodiment 61: Use of the compounds of Embodiments 1 to 12 or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers in the preparation of a pharmaceutical for the treatment or prevention of a target protein-mediated disorder, disease or condition in a subject.

[0300] Embodiment 62: Compounds of Embodiments 1 to 12 or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers thereof for use in the treatment or prevention of a target protein-mediated disorder, disease or condition in an object.

[0301] Embodiment 63: A compound of Embodiment 35 or Embodiment 35A or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders and infectious diseases or disorders, in which such treatment or prevention is required.

[0302] Embodiment 64: Compounds of Embodiment 35 or Embodiment 35A or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers thereof for use in the treatment or prevention of cancer.

[0303] Embodiment 65: Use of the compounds of Embodiment 35 or Embodiment 35A or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers in the preparation of a pharmaceutical for the treatment or prevention of a target protein-mediated disorder, disease or condition in a subject.

[0304] Embodiment 66: A compound of Embodiment 35 or Embodiment 35A, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment or prevention of a target protein-mediated disorder, disease or condition in an object.

[0305] Embodiment 67: A method for treating or preventing cancer in a subject, comprising administering any one compound from Embodiments 1 to 12 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0306] Embodiment 68: A compound that can bind to the cereblon complex and alter its specificity to induce ubiquitination and degradation of complex-related proteins, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0307] Embodiment 69: A compound according to Embodiment 68, comprising (i) a tris-tryptophan pocket binding portion that binds to the tris-tryptophan pocket of cereblon E3 ligase; and (ii) a target affinity portion covalently bonded to the tris-tryptophan pocket binding portion that interacts with the surface of cereblon E3 ligase, alters its surface, and causes the ligase to have affinity for a target protein.

[0308] Embodiment 70: Formula (I): [ka] (In the formula, [ka] It is either a single bond or a double bond; R d1 H, -CH2OC(O)R 15 -CH2OP(O)OHOR 15 or -CH2OP(O)(R 15 )2; R d2 H, C 1~6 Alkyl, halogen, C 1~6 Haloalkyl or C 1~6 It is heteroalkyl; R d3 teeth, [ka] [ka] and; A 1 This is a 5- or 6-membered heterocycline or NR that optionally contains 1 to 3 additional heteroatoms selected from O, N, and S. 1k , optionally containing 1 to 3 additional heteroatoms selected from O and S, and 1 to 3 R 1d It is a 5-membered heteroaryl substituted with; A 2 C 5~7 Carbocyclyl or N, NR 1k , a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O and S, and carbocykrill and heterocyclyl contain 1-3 R 1d It has been replaced with; X 1 , NR 4 or S; X 2 and X2a Each of them operates independently, CR 1a or N; Each X 3 CR is independent. 1d or N, and two or fewer X 3 is N; Each X 3’ CR is independent. 1d , CR 1c or N, and two or fewer X 3 is N and at least one X 3’ CR 1c and; Each X 4 CR is independent. 1d or N, and at least one X 4 is N, and there are two or fewer X 4 is N; Each X 5 CR is independent. 1a or N, and two or fewer X 5 is N; X 6 , NR 1k , O or S; X 7 , NR 4 , O or S; R 1a and R 1b These are H and C, respectively, independently. 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 Haloalkoxy, -NH2, -NH(C) 1~3 Alkyl), -N(C 1~3 Alkyl)2,-CN,F, orCl; R 1c C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4-C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1c’ C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, F, Cl, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; Each R 1d H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7-NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 - Selected from 5- or 6-membered heteroaryls, the alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1e C 2~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 It is a haloalkoxy, -CN, F, or Cl; R 1f C 1~3 Alkyl, C 1~3 Haloalkyl, C 1~3 Alkoxy, C 1~3 It is a haloalkoxy, -CN, F, or Cl; R 1g C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2)0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1g’ C 2~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 2~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted, and heterocyclyls have 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1h C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10-NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryls, alkynyls have 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1h’ C 4~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 2~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -C 6~10 Ariel, -(CH2) 2~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3(CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted, and heterocyclyls have 1 to 5 R 5 Substituted with, and carbocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1i H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2)0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R 1j H, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 NR 3 (CH2) 0~4 -5-7 member heterocycline, -(CH2) 0~4 NR 3 (CH2) 0~4 -C 6~10(CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 NR 3 (CH2) 0~4 -5 or 6-membered heteroaryl, -(CH2) 0~4 -NR 3 C(O)-C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~4 -NR 3 C(O)-5~7 member heterocycline, -(CH2) 0~4 -NR 3 C(O)-C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH2) 0~4 -C 3~7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S 3 C(O)O(CH2) 0~4 -5-7 member heterocycline, -NR 3 C(O)O(CH2) 0~4 -C 6~10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH2) 0~4 -5 or 6-membered heteroaryl, and alkynyl has 1 to 3 R 2 It is optionally substituted with, and carbocyclyl, heterocyclyl, aryl and heteroaryl, 1 to 5 R 5 It is optionally replaced by; R on the benzoxazole ring 1d , R 1i and R 1j It is not possible for all of them to be H at the same time; Each R 1k H and C are independent of each other. 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C1~3 Haloalkoxy, halogen, CN, -C(O)OH, -C(O)OC 1~6 Alkyl, -(CH2) 0~4 -C(O)NH2, -(CH2) 0~4 -C(O)NH(R 13 ), -(CH2) 0~4 -C(O)N(R 13 )2, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 C 6~10 (CH2) contains 1 to 3 heteroatoms selected from aryl, O, N, and S. 0~6 -5 or 6-membered heteroaryl, -C(O)O(CH2) 0~4 -C 3~7 -C(O)O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~4 -5-7 member heterocycline, -C(O)O(CH2) 0~4 -C 6~10 -C(O)O(CH2) containing aryl or 1 to 3 heteroatoms selected from O, N, and S 0~4 - Selected from 5- or 6-membered heteroaryls, the alkynyl is optionally substituted with 1 to 3 R2s, and the carbocyclyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with 1 to 5 R2s. 5 It is optionally replaced by; Each R 2 These are independently NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NHS(O)2R 9 or -NR 9 S(O)2R 9 and; R 3is H or C 1~6 It is alkyl; R 4 is H or C 1~6 It is alkyl; Each R 5 Independently, C 1~6 Alkyl, C 2~6 Alkenil, C 2~6 Alkinyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkyl, halogen, -OH, -C(O)H, -C(O)(C 1~6 Alkyl), -C(O)(C 6~10 aryl), -C(O)(5 or 6-membered heteroaryl), -C(O)(C 3~7 Carbocyclyl), -C(O)(5-7 member heterocyclyl), -(CH2) 0~3 C(O)OC 1~6 Alkyl, -C(O)NH2, -C(O)NH(C 1~6 Alkyl), -C(O)N(C 1~6 Alkyl)2,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2,-NHC(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -NHS(O)2R 9 , -NR 9 S(O)2R 9 , -S(O) q NHR 9 , -S(O) q N(R 9 )2, -S(O) q R 9 , C 1~6 Hydroxyalkyl, -O(CH2) 1~3 CN, CN, -O(CH2) 0~6 -C 3~7 -O(CH2) contains 1 to 3 heteroatoms selected from carbocyrill, O, N, and S. 0~6 -5-7 member heterocycline, -O(CH2) 0~3(C6~C 10 -O(CH2) containing 1 to 3 heteroatoms selected from aryl, adamantyl, O, N, and S 0~3 -5 or 6-membered heteroaryl, -(CH2) 0~6 -C 3~7 Carbocyclyl, containing 1 to 3 heteroatoms selected from O, N, and S - (CH2) 0~6 -5-7 member heterocycline, -(CH2) 0~6 -C 6~10 -(CH2) containing an aryl group and 1 to 3 heteroatoms selected from O, N, and S. 0~6 -5 or 6-membered heteroaryl, alkyl is 1-3 R 6 It is optionally substituted, and carbocyclyl, heterocyclyl, aryl and heteroaryl have 1 to 4 R 8 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 3~7 It forms a carbocyryl or a 5-7 membered heterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and the carbocyryl and heterocyclyl contain 1-3 R 6 It is either optionally replaced by; or two R 5 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S; or 2 R 5 If they are on the same atom, then together with the atom to which they are attached, C 3~7 Spirocarbocyryl or 5-7 membered spiroheterocyclyl containing 1-3 heteroatoms selected from O, N, and S, and spirocarbocyryl and spiroheterocyclyl contain 1-4 R 10 It is either optionally replaced by; or two R 5 If they are on the same atom, they form (O); R 6 -NH2, -NH(C 1~6 Alkyl), -N(C 1~6 Alkyl)2, C6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 7 It is optionally replaced by; Each R 7 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, or C 6~10 It is an allele; Each R 8 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy, halogen, or -OH; R 9 C 1~6 Alkyl, C 1~6 Haloalkyl, 5-7 membered heterocycline containing 1-3 heteroatoms selected from O, N, and S, C 6~10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 11 It is optionally replaced by; Each R 10 C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 It is a haloalkoxy or halogen; or Two R's 10 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forming a 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S; Each R 11 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~6 Haloalkoxy, -NHC(O)(C)1~6 Alkyl), -N(C 1~6 Alkyl)C(O)(C 1~6 It is alkyl or halogen; or Two R's 11 If they are on adjacent atoms, then together with the atoms to which they are attached, C 6~10 Forms a 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, and the aryl and heteroaryl contain 1 to 3 R 12 It is optionally replaced by; Each R 12 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy or C 1~3 It is a haloalkoxy; R 13 Each of these occurrences is independent of C 1~6 Alkyl, C 1~6 Haloalkyl, C 6~10 A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the alkyl has 1 to 2 C 1~6 They are optionally substituted with alkoxys, and aryls and heteroaryls have 1 to 3 R 14 It is optionally replaced by; Each R 14 Independently, C 1~6 Alkyl, C 1~6 Haloalkyl, C 1~6 Alkoxy, C 1~3 Haloalkoxy, halogen, C 6~10 A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S; R 15 is H or C 1~6 It is alkyl; and (q is 0, 1, or 2) Compounds relating to Embodiment 68 or 69, or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof, having the above characteristics.

[0309] Embodiment 71:R d1 The compound according to embodiment 70, wherein H is present.

[0310] Embodiment 72:R d1 is -CH2OC(O)R 15 -CH2OP(O)OHOR 15 or -CH2OP(O)(R 15 )2, the compound according to embodiment 70.

[0311] Embodiment 73:R d2 A compound according to any one of embodiments 70 to 72, wherein H is present.

[0312] Embodiment 74:R d1 and R d2 Each of these is independently a compound according to any one of embodiments 70 to 73, wherein each is H.

[0313] Embodiment 75:R 1d A compound according to any one of embodiments 70 to 74, wherein H is present.

[0314] Embodiment 76:R d3 teeth, [ka] [ka] [ka] [ka] [ka] [ka] A compound according to any one of embodiments 70 to 75.

[0315] Embodiment 77:R d3 teeth, [ka] [ka] [ka] A compound according to any one of embodiments 70 to 76.

[0316] Embodiment 78: [ka] [ka] [ka] A compound according to any one of embodiments 70 to 77, having a formula selected from the above, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0317] Embodiment 79: 1-(benzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-ethinylbenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-ethinylbenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-iodobenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-iodobenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; Phenyl(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-5-yl)carbamate; 1-(6-chloropyrazolo[1,5-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-(1-benzyl-1,2,3,6-tetrahydropyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-(1-(4-(tert-butyl)benzoyl)-1,2,3,6-tetrahydropyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-(1-benzylpiperidine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-(3-(dimethylamino)prop-1-in-1-yl)benzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; N-benzyl-3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-6-carboxamide; 1-(6-methylbenzo[d]isoxazole-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-chlorobenzo[d]isoxazole-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-(4-methylphenethoxy)benzo[d]isoxazole-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-(1-benzylpiperidine-4-yl)quinoline-3-yl)pyrimidine-2,4(1H,3H)-dione; 1-(7-(1-benzyl-1,2,3,6-tetrahydropyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)pyrimidine-2,4(1H,3H)-dione; and 1-(7-bromoimidazo[1,2-a]pyridine-3-yl)pyrimidine-2,4(1H,3H)-dione A compound according to any one of embodiments 68 to 78, selected from the above, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0318] Embodiment 80: A pharmaceutical composition comprising a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

[0319] Embodiment 81: A pharmaceutical composition according to Embodiment 80, further comprising at least one additional pharmaceutical product.

[0320] Embodiment 82: A pharmaceutical composition according to Embodiment 80 or Embodiment 81 for use in the treatment or prevention of disorders, diseases, or conditions mediated by cereblon.

[0321] Embodiment 83: A pharmaceutical composition of Embodiment 80 or Embodiment 81 for use in the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, or infectious diseases or disorders.

[0322] Embodiment 84: A method for preparing cereblon in a biological sample, comprising contacting the sample with a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof.

[0323] Embodiment 85: A method for inducing ubiquitination and degradation of a complex-related protein selected from the group listed in Table 1 in a biological sample by binding to and altering the specificity of a cereblon complex, comprising contacting the sample with a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0324] Embodiment 86: A method for treating or preventing a cereblon-mediated disorder, disease, or condition in a subject, comprising administering a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0325] Embodiment 87: The method according to Embodiment 86, wherein the disorder, disease, or condition is a respiratory disorder, proliferative disorder, autoimmune disorder, autoinflammatory disorder, inflammatory disorder, neurological disorder, or infectious disease or disorder.

[0326] Embodiment 88: The method according to Embodiment 87, wherein the disorder, disease, or condition is a proliferative disorder.

[0327] Embodiment 89: The method according to Embodiment 88, wherein the proliferative disorder is cancer.

[0328] Embodiment 90: The method according to Embodiment 87, wherein the disorder, disease, or condition is a neurological disorder.

[0329] Embodiment 91: A method for treating or preventing respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, or infectious diseases or disorders in a subject in need thereof, comprising administering a therapeutically effective amount of a compound relating to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0330] Embodiment 92: The method according to Embodiment 91, wherein the disorder or disease is a proliferative disorder.

[0331] Embodiment 93: The method according to Embodiment 92, wherein the proliferative disorder is cancer.

[0332] Embodiment 94: The method according to Embodiment 91, wherein the disorder or disease is a neurological disorder.

[0333] Embodiment 95: Use of a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the preparation of a pharmaceutical for the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, or infectious diseases or disorders in a subject requiring such treatment or prevention.

[0334] Embodiment 96: Use of a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the preparation of a pharmaceutical for the treatment or prevention of cancer.

[0335] Embodiment 97: A method for degrading a target protein in a biological sample, comprising contacting the target protein with a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein the target protein is selected from the group listed in Table 1.

[0336] Embodiment 98: A method for treating or preventing a target protein-mediated disorder, disease, or condition in a subject, comprising administering a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0337] Embodiment 99: The method according to Embodiment 98, wherein the disorder, disease, or condition is a proliferative disorder.

[0338] Embodiment 100: The method according to Embodiment 99, wherein the proliferative disorder is cancer.

[0339] Embodiment 101: The method according to Embodiment 98, wherein the disorder, disease, or condition is a neurological disorder.

[0340] Embodiment 102: A method for treating or preventing cancer in a subject, comprising administering a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof to the subject.

[0341] Embodiment 103: A compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders or infectious diseases or disorders in subjects requiring such treatment or prevention.

[0342] Embodiment 104: A compound according to any one of Embodiments 68 to 79, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the treatment or prevention of cancer.

[0343] Embodiment 105: Use of a compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof in the preparation of a pharmaceutical for the treatment or prevention of a target protein-mediated disorder, disease or condition in a subject.

[0344] Embodiment 106: A compound according to any one of Embodiments 68 to 79 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof for use in the treatment or prevention of a target protein-mediated disorder, disease or condition in an object.

[0345] In one embodiment, the target protein includes a beta hairpin.

[0346] In one embodiment, the target protein is a beta-turn-containing protein. In another embodiment, the beta-turn-containing protein is a protein selected from the group listed in Table 1.

[0347] In one embodiment, the target protein is selected from the group consisting of the following:

[0348] [Table 7]

[0349] [Table 8]

[0350] [Table 9]

[0351] [Table 10]

[0352] [Table 11]

[0353] [Table 12]

[0354] [Table 13]

[0355] [Table 14]

[0356] [Table 15]

[0357] [Table 16]

[0358] Table 17

[0359] Table 18

[0360] Table 19

[0361] Table 20

[0362] Table 21

[0363] Table 22

[0364] Table 23

[0365] Table 24

[0366] Table 25

[0367] Table 26

[0368] Table 27

[0369] Table 28

[0370] Table 29

[0371] Table 30

[0372] Table 31

[0373] Table 32

[0374] Table 33

[0375] Table 34

[0376] Table 35

[0377] Table 36

[0378] Table 37

[0379] Table 38

[0380] Table 39

[0381] Table 40

[0382] Table 41

[0383] Table 42

[0384] Table 43

[0385] Table 44

[0386] Table 45

[0387] Table 46

[0388] Table 47

[0389] Table 48

[0390] Table 49

[0391] Table 50

[0392] Table 51

[0393] Table 52

[0394] Table 53

[0395] Table 54

[0396] Table 55

[0397] Table 56

[0398] Table 57

[0399] Table 58

[0400] Table 59

[0401] Table 60

[0402] Table 61

[0403] Table 62

[0404] Table 63

[0405] Table 64

[0406] Table 65

[0407] Table 66

[0408] Table 67

[0409] Table 68

[0410] Table 69

[0411] Table 70

[0412] Table 71

[0413] Table 72

[0414] Table 73

[0415] Table 74

[0416] Table 75

[0417] Table 76

[0418] Table 77

[0419] Table 78

[0420] Table 79

[0421] Table 80

[0422] Table 81

[0423] Table 82

[0424] Table 83

[0425] Table 84

[0426] Table 85

[0427] Table 86

[0428] Table 87

[0429] Table 88

[0430] Table 89

[0431] Table 90

[0432] Table 91

[0433] Table 92

[0434] Table 93

[0435] Table 94

[0436] Table 95

[0437] Table 96

[0438] Table 97

[0439] Table 98

[0440] Table 99

[0441] Table 100

[0442] Table 101

[0443] Table 102

[0444] Table 103

[0445] Table 104

[0446] Table 105

[0447] Table 106

[0448] Table 107

[0449] Table 108

[0450] Table 109

[0451] Table 110

[0452] Table 111

[0453] Table 112

[0454] Table 113

[0455] Table 114

[0456] Table 115

[0457] Table 116

[0458] Table 117

[0459] Table 118

[0460] Table 119

[0461] Table 120

[0462] Table 121

[0463] Table 122

[0464]

Table 123

[0465] Table 124

[0466] Table 125

[0467] Table 126

[0468] Table 127

[0469] Table 128

[0470] Table 129

[0471] Table 130

[0472] Table 131

[0473] Table 132

[0474] Table 133

[0475] Table 134

[0476] Table 135

[0477] Table 136

[0478] Table 137

[0479] Table 138

[0480] Table 139

[0481] Table 140

[0482] Table 141

[0483] Table 142

[0484] Table 143

[0485] Table 144

[0486] Table 145

[0487] Table 146

[0488] Table 147

[0489] Table 148

[0490] Table 149

[0491] Table 150

[0492] Table 151

[0493] In other embodiments of the present disclosure, the compounds of the present disclosure are enantiomers. In some embodiments, the compounds are (S)-enantiomers. In other embodiments, the compounds are (R)-enantiomers. In yet other embodiments, the compounds of the present disclosure may be (+) or (-) enantiomers.

[0494] It should be understood that all isomers, including mixtures thereof, are included in this disclosure. If a compound contains a double bond, the substituent will be in an E or Z configuration. If a compound contains a disubstituted cycloalkyl group, the cycloalkyl substituent may have a cis or trans configuration. All tautomers are also intended to be included.

[0495] The compounds of this disclosure, as well as their pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, and prodrugs, may exist in tautomer forms (e.g., amides or iminoethers). All such tautomers are contemplated herein as part of this disclosure.

[0496] The compounds of this disclosure may contain asymmetric or chiral centers and therefore may exist in different stereoisomers. All stereoisomers of the compounds of this disclosure, as well as their mixtures, including racemic mixtures, are intended to form part of this disclosure. Furthermore, this disclosure encompasses all geometric and positional isomers. For example, where a compound of this disclosure incorporates a double bond or fused ring, both cis and trans forms, as well as mixtures, are included within the scope of this disclosure. Each compound disclosed herein includes all enantiomers that correspond to the general structure of the compound. The compounds may be racemic, enantiomerically pure, or other forms from a stereochemical standpoint. Analytical results may reflect data collected for racemic, enantiomerically pure, or other forms from a stereochemical standpoint.

[0497] Diastereomer mixtures can be separated into individual diastereomers based on physicochemical differences by methods well known to those skilled in the art, such as chromatography and / or fractional crystallization. Enantiomers can be separated by reacting the enantiomer mixture with a suitable optically active compound (e.g., a chiral auxiliary such as a chiral alcohol or mochelate chloride) to convert the enantiomer mixture into a diastereomer mixture, and then separating the diastereomers to convert the individual diastereomers into their corresponding pure enantiomers (e.g., by hydrolysis). Some compounds of this disclosure may also be atropisomers (e.g., substituted biaryls) and are considered part of this disclosure. Enantiomers can also be separated using a chiral HPLC column.

[0498] The compounds disclosed herein may exist in different tautomer forms, all of which are encompassed within the scope of this disclosure, chemical structure, and nomenclature. Furthermore, for example, all keto-enol and imine-enamine forms of the compounds are included in this disclosure.

[0499] All stereoisomers of the compound (including salts, solvates, esters, and prodrugs of the compound, as well as salts, solvates, and esters of prodrugs), including enantiomers (which may exist even in the absence of a chiral carbon), rotational isomers, atropisomers, and diastereomers, which may exist due to chiral carbons on various substituents, are intended to be within the scope of this disclosure, as are positional isomers (e.g., 4-pyridyl and 3-pyridyl), including those that may exist due to chiral carbons on various substituents, such as enantiomers (which may exist even in the absence of a chiral carbon), rotational isomers, atropisomers, and diastereomers (which may exist due to chiral carbons on various substituents), (e.g., geometric isomers, optical isomers, etc.). (For example, if the compound of formula (I) incorporates a double bond or a fused ring, both cis and trans forms and mixtures thereof are within the scope of this disclosure. Also, for example, all keto-enol and imine-enamine forms of the compound are included in this disclosure.) Individual stereoisomers of the compounds of this disclosure may, for example, substantially contain no other isomers, or may be mixed, for example, as a racemate or with all or other selected stereoisomers.

[0500] The chiral centers of the compounds of this disclosure may have an S or R configuration as defined by the IUPAC 1974 recommendation. In certain embodiments, each asymmetric atom has at least a 50% enantiomeric excess, at least a 60% enantiomeric excess, at least a 70% enantiomeric excess, at least an 80% enantiomeric excess, at least a 90% enantiomeric excess, at least a 95% enantiomeric excess, or at least a 99% enantiomeric excess in the (R)- or (S)- configuration. Substituents of atoms having an unsaturated double bond may, where possible, be present in cis-(Z)- or trans-(E)- form.

[0501] The use of terms such as "salt," "solvate," "ester," and "prodrug" is intended to apply similarly to salts, solvates, esters, and prodrugs of enantiomers, stereoisomers, rotational isomers, tautomers, positional isomers, racemates, or prodrugs of the compounds of the present invention.

[0502] The compounds of this disclosure may form salts which are also within the scope of this disclosure. References to compounds in formulas herein are generally understood to include references to their salts unless otherwise specified.

[0503] Compounds and intermediates can be isolated and used as compounds themselves. All formulas given herein are intended to represent both the isotopically labeled and unlabeled forms of the compounds. Isotope-labeled compounds have the structure depicted by the formulas shown herein, except that one or more atoms are replaced by atoms having selected atomic masses or mass numbers. Examples of isotopes that can be incorporated into the compounds of this disclosure include hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and each of the following. 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 18 F, 31 P, 32 This disclosure includes isotopes such as P. This disclosure covers various isotope-labeled compounds as defined herein, for example 3 H,13 C and 14 This includes compounds containing radioactive isotopes such as 13C. Such isotope-labeled compounds are used in drug or substrate tissue distribution assays, or in metabolic studies during radiation therapy of patients. 14 (using C), reaction kinetics research ( 2 H or 3 Using H, it is useful for detection or imaging techniques such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In particular, 18 F, 11 C or labeled compounds may be particularly desirable for PET or SPECT studies.

[0504] Furthermore, heavier isotopes, especially deuterium ( 2 Substitution with H or D may yield certain therapeutic benefits due to improved metabolic stability. For example, in vivo, these may include extension of half-life, reduction of required dose, reduction of CYP450 inhibition (competitive or time-dependent), or improvement of the therapeutic index. For example, substitution with deuterium may modulate undesirable side effects of non-deuterated compounds, such as competitive CYP450 inhibition or time-dependent CYP450 inactivation. In this regard, it is understood that deuterium is considered a substituent in the compounds of this disclosure. The concentration of such heavier isotopes, particularly deuterium, may be defined by the isotopic enrichment factor. As used herein, the term “isotopic enrichment factor” means the ratio of the isotopic abundance to the native abundance of a particular isotope. Where a substituent in a compound of the present disclosure is represented as deuterium, such compound has an isotopic enrichment factor of at least 3500 (52.5% deuterium incorporation at each designated deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation) for each designated deuterium atom.

[0505] The isotope-labeled compounds of this disclosure can generally be prepared by the procedures disclosed in the scheme or examples and preparations, either by the prior art well known to those skilled in the art, or by using appropriate isotope-labeled reagents instead of the non-isotopically labeled reagents described below.

[0506] Pharmaceutically acceptable solvates in accordance with this disclosure include those in which the crystallization solvent is isotope-substituted, such as D2O, d6-acetone, and d6-DMSO.

[0507] In some embodiments, the degradation of the target protein is performed by EC 50 It is measured by [method].

[0508] Effectiveness is, EC 50 It can be determined by the value. If determined under substantially similar decomposition conditions, a lower EC 50 Compounds with a higher EC value 50 It is a more potent degrading agent compared to compounds with a value. In some embodiments, substantially similar conditions include determining protein-level degradation in cells expressing a particular protein or any fragment thereof.

[0509] This disclosure covers the compounds described herein and their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers, as well as pharmaceutical compositions comprising one or more of the compounds described herein or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers.

[0510] E. Method using the compound of formula (I) The compounds and compositions described herein are generally useful for modulating CRBN. Another aspect of the disclosure relates to a method for modulating a target protein in a subject requiring such modification, the method comprising administering a therapeutically effective amount of a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, or a pharmaceutical composition comprising a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, to a subject. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0511] In another embodiment, the disclosure relates to a method for inhibiting a target protein in a subject requiring such inhibition, the method comprising administering to a subject a therapeutically effective amount of a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, or a pharmaceutical composition comprising a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0512] Another aspect of the present disclosure relates to a method for modulating or inhibiting a target protein in a subject where such modification is required, the method comprising administering to a subject a therapeutically effective amount of a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, or a pharmaceutical composition comprising a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0513] In another embodiment, the Disclosure relates to a method for treating or preventing respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders, and infectious diseases or disorders mediated by target proteins in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, or a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the disorder is mediated by a target protein listed in Table 1.

[0514] Another aspect of the present disclosure relates to a method for treating or preventing cancer in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, or a pharmaceutical composition comprising a compound disclosed herein or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0515] In another aspect, the Disclosure relates to the use of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (I The present invention provides compounds of (v), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0516] Another aspect of this disclosure relates to the use of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), for use in inhibiting a target protein in a subject where such inhibition is desired. The present invention relates to compounds of (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18, or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0517] In another aspect, the Disclosure relates to the use of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), ( The present invention provides a pharmaceutical composition comprising a compound of Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0518] Another aspect of this disclosure relates to the use of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw) for inhibiting target proteins in subjects where such inhibition is desired. The present invention relates to a pharmaceutical composition comprising compounds of (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0519] In another aspect, the present disclosure relates to the use of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), for use in inhibiting target proteins in subjects where such inhibition is desired. The present invention relates to a pharmaceutical composition comprising a compound of (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or a compound I-1 to I-18 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0520] Another aspect of this disclosure relates to the use of formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (I) for use in subjects requiring treatment or prevention of respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders and infectious diseases or disorders mediated by target proteins, in subjects requiring such treatment or prevention. Compounds of k), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compound I-1 ~I-18 or its pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers, formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw) The present invention relates to pharmaceutical compositions comprising compounds of (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers. In one embodiment, the impairment is mediated by target proteins listed in Table 1.

[0521] In another aspect, the Disclosure relates to the formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It) for use in treating or preventing cancer in subjects in need thereof. Compounds of (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates, prostaglandins. Drugs, stereoisomers or tautomers, sometimes formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz) The present invention relates to pharmaceutical compositions comprising compounds of (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers. In one embodiment, cancer is mediated by target proteins listed in Table 1.

[0522] Another aspect of this disclosure relates to the manufacture of a pharmaceutical for inhibiting or modulating a target protein in a subject that requires it, using formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), ( Compounds of (I), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates. Prodrugs, stereoisomers or tautomers, or formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz) The present invention relates to a pharmaceutical composition comprising compounds of (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0523] In another aspect, the Disclosure relates to the manufacture of a pharmaceutical for inhibiting a target protein in a subject that requires it, using formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It Compounds of (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18 or their pharmaceutically acceptable salts, hydrates, solvates, prostaglandins. Drugs, stereoisomers or tautomers, sometimes formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Ix), (Iy), (Iz), The present invention relates to the use of pharmaceutical compositions comprising compounds of (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compounds I-1 to I-18, or their pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers. In one embodiment, the target protein is a target protein selected from one of the target proteins listed in Table 1.

[0524] Another aspect of the present disclosure relates to the manufacture of a pharmaceutical product for treating a disorder, disease, or condition mediated by a target protein in a subject requiring such treatment, using formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw The present invention relates to the use of a pharmaceutical composition comprising a compound of (Ix), (Iy), (Iz), (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak), (Ial), or (Iam), or compound I-1 to I-18 or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, and a pharmaceutically acceptable carrier. In one embodiment, the disorder, disease or condition mediated by the target protein is selected from respiratory disorders, proliferative disorders, autoimmune disorders, autoinflammatory disorders, inflammatory disorders, neurological disorders and infectious diseases or disorders. In one embodiment, the proliferative disorder is cancer.

[0525] In another aspect, the Disclosure relates to the manufacture of a pharmaceutical for treating or preventing cancer mediated by a target protein in a subject in need thereof, using formulas (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (Il), (Im), (In), (Io), (Ip), (Iq), (I Comp...

Claims

1. A compound or a pharmaceutically acceptable salt or tautomer thereof that can bind to cereblon E3 ligase and cause the ligase to have affinity for a target protein, The target protein is selected from IKZF1, GSPT1, and SALL4. The aforementioned compound is as follows: 【Chemistry 1】 【Chemistry 2】 (In the above formula, R 1a and R 1b are each independently H, C 1 to 3 alkyl, C 1 to 3 haloalkyl, C 1 to 3 alkoxy, C 1 to 3 haloalkoxy, -NH 2 , -NH(C 1 to 3 alkyl), -N(C 1 to 3 alkyl) 2 , -CN, F or Cl; R 1c C 1 ~ 6 Alkyl, C 2 ~ 6 Alkinyl, C 1 ~ 6 Haloalkyl, halogen, CN, -C(O)OH, -C(O)OC 1 ~ 6 Alkyl, -(CH 2 ) 0 ~ 4 -C(O)NH 2 ,-(CH 2 ) 0 ~ 4 -C(O)NH(R) 13 ), - (CH 2 ) 0 ~ 4 -C(O)N(R) 13 ) 2 ,-(CH 2 ) 0 ~ 6 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 6 -5-7 member heterocyclyl, -(CH 2 ) 0 ~ 6 C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 6 -5 or 6-membered heteroaryl, -(CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -5- to 7-member heterocyclyl, -(CH 2 ) 0 to 4 NR 3 (CH 2 ( 0 to 4 -C 6 to 10 aryl, O, N, and S, containing one to three heteroatoms selected from the group consisting of -(CH 2 ( 0 to 4 NR 3 (CH 2 ( 0 to 4 -5- or 6-member heteroaryl, -(CH 2 ( 0 to 4 -NR 3 C(O)-C 3 to 7 carbocyclyl, O, N, and S, containing one to three heteroatoms selected from the group consisting of -(CH 2 ( 0 to 4 -NR 3 C(O)-5- to 7-member heterocyclyl, -(CH 2 ( 0 to 4 -NR 3 C(O)-C 6 to 10 aryl, O, N, and S, containing one to three heteroatoms selected from the group consisting of -(CH 2 ( 0 to 4 -NR 3 C(O)-5- or 6-member heteroaryl, -NR 3 C(O)O(CH 2 ( 0 to 4 -C 3 to 7 carbocyclyl, O, N, and S, containing one to three heteroatoms selected from the group consisting of -NR 3 C(O)O(CH 2 ( 0 to 4 -5- to 7-member heterocyclyl, -NR 3 C(O)O(CH 2 ( 0 to 4 -C 6 to 10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH 2 ) 0 ~ 4 - A 5- or 6-membered heteroaryl, wherein the alkynyl has 1 to 3 R 2 The carbocyryl, heterocyclyl, aryl, and heteroaryl are optionally substituted, and each of the carbocyryl, heterocyclyl, aryl, and heteroaryl has 1 to 5 R 5 It is optionally replaced by; R 1c' is, -(CH 2 ) 0 ~ 6 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 6 -5-7 member heterocyclyl, -(CH 2 ) 0 ~ 6 C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 6 -5 or 6-membered heteroaryl, -(CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -5-7 member heterocyclyl, -(CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -5 or 6-membered heteroaryl, -(CH 2 ) 0 ~ 4 -NR 3 C(O)-C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 4 -NR 3 C(O)-5-7 member heterocyclyl, -(CH 2 ) 0 ~ 4 -NR 3 C(O)-C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH 2 ) 0 ~ 4 -C 3 ~ 7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S. 3 C(O)O(CH 2 ) 0 ~ 4 - 5- to 7-membered heterocyclyl, - NR 3 C(O)O(CH 2 ) 0 ~ 4 -C 6 ~ 10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH 2 ) 0 ~ 4 - A 5- or 6-membered heteroaryl, wherein the alkynyl has 1 to 3 R 2 The carbocyryl, heterocyclyl, aryl, and heteroaryl are optionally substituted, and each of the carbocyryl, heterocyclyl, aryl, and heteroaryl has 1 to 5 R 5 It is optionally replaced by; R 1d H is; R 1e C 2 ~ 3 Alkyl, C 1 ~ 3 Haloalkyl, C 1 ~ 3 Alkoxy, C 1 ~ 3 It is a haloalkoxy, -CN, F, or Cl; R 1i H, C 1 ~ 6 Alkyl, C 2 ~ 6 Alkenil, C 2 ~ 6 Alkinyl, C 1 ~ 6 Haloalkyl, CN, -C(O)OH, -C(O)OC 1 ~ 6 Alkyl, -(CH 2 ) 0 ~ 4 -C(O)NH 2 ,-(CH 2 ) 0 ~ 4 -C(O)NH(R) 13 ), - (CH 2 ) 0 ~ 4 -C(O)N(R) 13 ) 2 ,-(CH 2 ) 0 ~ 6 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 6 -5-7 member heterocyclyl, -(CH 2 ) 0 ~ 6 C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 6 -5 or 6-membered heteroaryl, -(CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -5-7 member heterocyclyl, -(CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -5 or 6-membered heteroaryl, -(CH 2 ) 0 ~ 4 -NR 3 C(O)-C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 4 -NR 3 C(O)-5-7 member heterocyclyl, -(CH 2 ) 0 ~ 4 -NR 3 C(O)-C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH 2 ) 0 ~ 4 -C 3 ~ 7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S. 3 C(O)O(CH 2 ) 0 ~ 4 - 5- to 7-membered heterocyclyl, - NR 3 C(O)O(CH 2 ) 0 ~ 4 -C 6 ~ 10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH 2 ) 0 ~ 4 - Selected from 5- or 6-membered heteroaryls, the alkynyl has 1 to 3 R 2 The carbocyryl, heterocyclyl, aryl, and heteroaryl are optionally substituted, and each of the carbocyryl, heterocyclyl, aryl, and heteroaryl has 1 to 5 R 5 It is optionally replaced by; R 1j H, C 1 ~ 6 Alkyl, C 2 ~ 6 Alkenil, C 2 ~ 6 Alkinyl, C 1 ~ 6 Haloalkyl, halogen, CN, -C(O)OH, -C(O)OC 1 ~ 6 Alkyl, -(CH 2 ) 0 ~ 4 -C(O)NH 2 ,-(CH 2 ) 0 ~ 4 -C(O)NH(R) 13 ), - (CH 2 ) 0 ~ 4 -C(O)N(R) 13 ) 2 ,-(CH 2 ) 0 ~ 6 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 6 -5-7 member heterocyclyl, -(CH 2 ) 0 ~ 6 C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 6 -5 or 6-membered heteroaryl, -(CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -5-7 member heterocyclyl, -(CH 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 4 NR 3 (CH 2 ) 0 ~ 4 -5 or 6-membered heteroaryl, -(CH 2 ) 0 ~ 4 -NR 3 C(O)-C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 4 -NR 3 C(O)-5-7 member heterocyclyl, -(CH 2 ) 0 ~ 4 -NR 3 C(O)-C 6 ~ 10 (CH) containing one to three heteroatoms selected from aryl, O, N, and S 2 ) 0 ~ 4 -NR 3 C(O)-5 or 6-membered heteroaryl, -NR 3 C(O)O(CH 2 ) 0 ~ 4 -C 3 ~ 7 -NR containing 1 to 3 heteroatoms selected from carbocyclyl, O, N, and S. 3 C(O)O(CH 2 ) 0 ~ 4 - 5- to 7-membered heterocyclyl, - NR 3 C(O)O(CH 2 ) 0 ~ 4 -C 6 ~ 10 -NR containing aryl or 1 to 3 heteroatoms selected from O, N, and S 3 C(O)O(CH 2 ) 0 ~ 4 - A 5- or 6-membered heteroaryl, wherein the alkynyl has 1 to 3 R 2 The carbocyryl, heterocyclyl, aryl, and heteroaryl are optionally substituted, and each of the carbocyryl, heterocyclyl, aryl, and heteroaryl has 1 to 5 R 5 It is optionally replaced by; R on the benzoxazole ring 1d , R 1i and R 1j It is not possible for all of them to be H at the same time; Each R 2 NH 2 ,-NH(C 1 ~ 6 Alkyl), -N(C 1 ~ 6 Alkyl) 2 , -C(O)NH 2 , -C(O)NH(C 1 ~ 6 Alkyl), -C(O)N(C 1 ~ 6 Alkyl) 2 ,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), - NHS (O) 2 R 9 or -NR 9 S(O) 2 R 9 And; R 3 is H or C 1 ~ 6 It is alkyl; R 4 is H or C 1 ~ 6 It is alkyl; R 5 Independently, C 1 ~ 6 Alkyl, C 2 ~ 6 Alkenil, C 2 ~ 6 Alkinyl, C 1 ~ 6 Haloalkyl, C 1 ~ 6 Alkoxy, C 1 ~ 3 Haloalkoxy, halogen, -OH, -C(O)H, -C(O)(C 1 ~ 6 Alkyl), -C(O)(C 6 ~ 10 aryl), -C(O)(5 or 6-membered heteroaryl), -C(O)(C 3 ~ 7 Carbocyclyl), -C(O)(5-7 member heterocyclyl), -(CH 2 ) 0 ~ 3 C(O)OC 1 ~ 6 Alkyl, -C(O)NH 2 , -C(O)NH(C 1 ~ 6 Alkyl), -C(O)N(C 1 ~ 6 Alkyl) 2 ,-NHC(O)R 9 , -N(R 9 )C(O)(R 9 ), -NH 2 ,-NH(C 1 ~ 6 Alkyl), -N(C 1 ~ 6 Alkyl) 2 , -NHC(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), - NHS (O) 2 R 9 , -NR 9 S(O) 2 R 9 , -S(O) q NHR 9 , -S(O) q N(R) 9 ) 2 , -S(O) q R 9 , C 1 ~ 6 Hydroxyalkyl, -O(CH 2 ) 1 ~ 3 CN, CN, -O(CH 2 ) 0 ~ 6 -C 3 ~ 7 -O(CH) containing one to three heteroatoms selected from carbocyrill, O, N, and S 2 ) 0 ~ 6 -5-7 member heterocyclyl, -O(CH 2 ) 0 ~ 3 (C 6 ~C 10 -O(CH) containing one to three heteroatoms selected from aryl, adamantyl, O, N, and S 2 ) 0 ~ 3 -5 or 6-membered heteroaryl, -(CH 2 ) 0 ~ 6 -C 3 ~ 7 A carbocyryl compound containing one to three heteroatoms selected from O, N, and S - (CH 2 ) 0 ~ 6 -5-7 member heterocyclyl, -(CH 2 ) 0 ~ 6 -C 6 ~ 10 (CH) containing an aryl group and one to three heteroatoms selected from O, N, and S. 2 ) 0 ~ 6 - A 5- or 6-membered heteroaryl, wherein the alkyl group has 1 to 3 R 3 The carbocyryl, heterocyclyl, aryl, and heteroaryl are optionally substituted, and each of the carbocyryl, heterocyclyl, aryl, and heteroaryl has 1 to 4 R 8 It is optionally replaced by; R 6 is, -NH 2 ,-NH(C 1 ~ 6 Alkyl), -N(C 1 ~ 6 Alkyl) 2 , C 6 ~ 10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 7 It is optionally replaced by; Each R 7 Independently, C 1 ~ 6 Alkyl, C 1 ~ 6 Haloalkyl, C 1 ~ 6 Alkoxy, C 1 ~ 3 Haloalkoxy, halogen, or C 6 ~ 10 It is an allele; Each R 8 Independently, C 1 ~ 6 Alkyl, C 1 ~ 6 Haloalkyl, C 1 ~ 6 Alkoxy, C 1 ~ 6 It is a haloalkoxy, halogen, or -OH; R 9 C 1 ~ 6 Alkyl, C 1 ~ 6 Haloalkyl, 5-7 membered heterocycline containing 1-3 heteroatoms selected from O, N, and S, C 6 ~ 10 A 5- or 6-membered heteroaryl containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl contain 1 to 3 R 11 It is optionally replaced by; Each R 11 Independently, C 1 ~ 6 Alkyl, C 1 ~ 6 Haloalkyl, C 1 ~ 6 Alkoxy, C 1 ~ 6 Haloalkoxy, -NHC(O)(C) 1 ~ 6 Alkyl), -N(C 1 ~ 6 Alkyl)C(O)(C 1 ~ 6 It is alkyl or halogen; or Two R's 11 If they are on adjacent atoms, then together with the atom to which they are attached, C 6 ~ 10 A 5- or 6-membered heteroaryl is formed, comprising aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl and heteroaryl have 1 to 3 R 12 It is optionally replaced by; Each R 12 Independently, C 1 ~ 6 Alkyl, C 1 ~ 6 Haloalkyl, C 1 ~ 6 Alkoxy or C 1 ~ 3 It is a haloalkoxy; R 13 Each of these occurrences is independent of C 1 ~ 6 Alkyl, C 1 ~ 6 Haloalkyl, C 6 ~ 10 A 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S, wherein the alkyl has 1 to 2 C 1 ~ 6 The aryl and heteroaryl are optionally substituted with alkoxy, and each has 1 to 3 R 14 It is optionally replaced by; Each R 14 Independently, C 1 ~ 6 Alkyl, C 1 ~ 6 Haloalkyl, C 1 ~ 6 Alkoxy, C 1 ~ 3 Haloalkoxy, halogen, C 6 ~ 10 (It is a 5- or 6-membered heteroaryl compound containing aryl or 1 to 3 heteroatoms selected from O, N, and S.) A compound having a formula selected from the following: The aforementioned compound, or a pharmaceutically acceptable salt or tautomer thereof.

2. The aforementioned compound, 1-(benzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-ethinylbenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-methylbenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-iodobenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-iodobenzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; Phenyl(3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-5-yl)carbamate; 1-(6-chloropyrazolo[1,5-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-(1-benzyl-1,2,3,6-tetrahydropyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-(1-(4-(tert-butyl)benzoyl)-1,2,3,6-tetrahydropyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-(1-benzylpiperidine-4-yl)imidazo[1,2-a]pyridine-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-(3-(dimethylamino)prop-1-in-1-yl)benzofuran-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; N-benzyl-3-(2,4-dioxotetrahydropyrimidine-1(2H)-yl)benzofuran-6-carboxamide; 1-(6-methylbenzo[d]isoxazole-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(5-chlorobenzo[d]isoxazole-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(6-(4-methylphenethoxy)benzo[d]isoxazole-3-yl)dihydropyrimidine-2,4(1H,3H)-dione; 1-(7-(1-benzyl-1,2,3,6-tetrahydropyridine-4-yl)imidazo[1,2-a]pyridine-3-yl)pyrimidine-2,4(1H,3H)-dione; and 1-(7-bromoimidazo[1,2-a]pyridine-3-yl)pyrimidine-2,4(1H,3H)-dione A compound selected from the above, or a pharmaceutically acceptable salt or tautomer thereof.

3. The compound has formula (Ic): 【Transformation 3】 The compound according to claim 1, which is a compound of the same, or a pharmaceutically acceptable salt or tautomer thereof.

4. The aforementioned compound is of formula (Ia): 【Chemistry 4】 The compound according to claim 1, which is a compound of the same, or a pharmaceutically acceptable salt or tautomer thereof.

5. The aforementioned compound is of formula (Ib): 【Transformation 5】 The compound according to claim 1, which is a compound of the same, or a pharmaceutically acceptable salt or tautomer thereof.

6. A pharmaceutical composition comprising a compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

7. The pharmaceutical composition according to claim 6, further comprising at least one additional pharmaceutical product.

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