Protein degradation compound based on nampt target protein and application thereof

A compound of Formula (I)

• or a salt, enantiomer, stereoisomer, solvate, isotopically enriched analog, prodrug, or polymorph thereof,
• wherein ULM is a E3 ligase ligand moiety, LIN is a linker moiety, the remaining moiety of the compound of Formula (I) is a nicotinamide phosphoribosyltransferase (NAMPT) ligand, and ULM is covalently bonded to NAMPT ligand through LIN;
• wherein ring A is the following groups:
• (Ra)m1 indicates that the ring A is optionally substituted by m1 Ra groups, wherein each Ra is independently hydroxyl, amino, halogen, or cyano, and m1 represents an integer of 0, 1, 2, 3, 4, or 5;
• R1 and R2 are the same or different and each independently represent H, cyano, or methyl;
• L1 represents substituted or unsubstituted linear C3-6 alkylene group, or substituted or unsubstituted linear C3-6 alkenylene group, wherein the optional substituents of the linear C3-6 alkylene group and the linear C3-6 alkenylene group are selected from the group consisting of C1-3 alkyl, halogen, C1-3 alkoxy, halogenated C1-3 alkyl, C1-3 alkyl-NHC(O)—, C1-3 alkyl-C(O)NH—, cyano, or any combination thereof;
• ring B is a 5- to 11-membered heterocyclylene group, and (Rb)m2 indicates that ring B is optionally substituted by m2 Rb groups, wherein each Rb is independently C1-3 alkyl, hydroxyl, amino, mercapto, halogen, C1-3 alkoxy, C1-3 alkylamino, halogenated C1-3 alkyl, amino-substituted C1-3 alkylene, C1-3 alkyl-NHC(O)—, C1-3 alkyl-C(O)NH—, or cyano, and m2 represents an integer of 0, 1, 2, 3, 4, or 5;
• ring C is a 5- to 10-membered heteroarylene group or a 6-membered arylene group, and (Rc)m3 indicates that ring C is optionally substituted by m3 Rc groups, wherein each Rc is independently C1-3 alkyl, C3-5 cycloalkyl, hydroxyl, amino, mercapto, halogen, C1-3 alkoxy, C1-3 alkylamino, halogenated C1-3 alkyl, amino-substituted C1-3 alkylene, C1-3 alkyl-NHC(O)—, C1-3 alkyl-C(O)NH—, or cyano, and m3 represents an integer of 0, 1, 2, 3, 4, or 5;
• m represents an integer of 0 or 1;
• and
• Y represents —N(R3)—, where R3 is H or C1-3 alkyl;
• or
• Y represents —O—;
• or
• Y is n connected rings D represented by the following formula:
• each ring D is independently a 5- to 11-membered heterocyclylene group, and (Rd)m4 indicates that each ring D is optionally independently substituted by m4 Rd groups, wherein each Rd is independently C1-3 alkyl, C3-6 cycloalkyl, hydroxyl, amino, mercapto, halogen, oxo, C1-3 alkoxy, C1-3 alkylamino, halogenated C1-3 alkyl, amino-substituted C1-3 alkylene, C1-3 alkyl-NHC(O)—, C1-3 alkyl-C(O)NH—, or cyano, and m4 represents an integer of 0, 1, 2, 3, 4, or 5;
• n represents an integer of 0, 1, 2, or 3, wherein when n represents an integer of 2 or 3, each ring D can be the same or different, and
• where m and n are not both 0 at the same time;
• with the proviso that the following compounds are excluded:
• the nicotinamide phosphoribosyltransferase (NAMPT) ligand represents the following structure:
• and
• ULM represents a structure of Formula (IV):
• wherein Z1 represents C(O) or Z1 represents a bond, and Z2 represents H or CH3.