Wee1 protein kinase degradation agent and use thereof

A compound represented by structural formula (I), or a derivative, pharmaceutically acceptable salt, isomer, solvate, hydrate, adduct, complex or prodrug thereof:

• W-L-D (I),
• wherein:
• W is a Wee1 kinase binding ligand with the following structure:
• wherein:
• represents an optionally substituted cyclic group;
• A1 is selected from O═, halogen, hydroxyl, nitro, cyano, amino, mercapto, C1-C6 alkyl, C1-C6 alkoxy, (mono- and di-C1-C6 alkylamino) C0-C4 alkyl;
• X2, for each occurrence, is independently selected from CR2′ or N;
• R2′, for each occurrence, is independently selected from absence, hydrogen, deuterium, halogen, hydroxyl, carbonyl, nitro, cyano, amino, mercapto, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 alkanoyl, C2-C6 alkylester, C1-C6 thioalkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy C1-C6 alkyl, amino C1-C6 alkyl, (mono- and di-C1-C6 alkylamino) C0-C4 alkyl, —C0-C4 alkyl (C3-C7 cycloalkyl), —O—C0-C4 alkyl (C3-C7 cycloalkyl), C3-C12 heterocyclyl, C6-C12 aryl, and C5-C10 heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, carbonyl, nitro, cyano, amino, mercapto, —COOH, or C1-C6 alkyl;
• R1, for each occurrence, is independently selected from absence, hydrogen, deuterium, halogen, hydroxyl, carbonyl, nitro, cyano, amino, mercapto, —COOH, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 alkanoyl, C2-C6 alkylester, C1-C6 thioalkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy C1-C6 alkyl, amino C1-C6 alkyl, (mono- and di-C1-C6 alkylamino) C0-C4 alkyl, —C0-C4 alkyl (C3-C7 cycloalkyl), —O—C0-C4 alkyl (C3-C7 cycloalkyl), C3-C12 heterocyclyl, C6-C12 aryl, and C5-C10 heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, carbonyl, nitro, cyano, amino, mercapto, —COOH, or C1-C6 alkyl;
• R2, for each occurrence, is independently selected from absence, hydrogen, deuterium, halogen, hydroxyl, carbonyl, nitro, cyano, amino, mercapto, —COOH, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C6 alkanoyl, C2-C6 alkylester, C1-C6 thioalkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxy C1-C6 alkyl, amino C1-C6 alkyl, (mono- and di-C1-C6 alkylamino) C0-C4 alkyl, —C0-C4 alkyl (C3-C7 cycloalkyl), —O—C0-C4 alkyl (C3-C7 cycloalkyl), C3-C12 heterocyclyl, C6-C12 aryl, and C5-C10 heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with 1, 2, 3, or 4 halogens, hydroxyl, carbonyl, nitro, cyano, amino, mercapto, —COOH, or C1-C6 alkyl;
• or
• R1 and R2 are joined together with the connected ring atoms to form a monocyclic, bicyclic or tricyclic saturated or unsaturated ring system with 5-14 ring atoms, wherein 0, 1, 2, 3 or 4 are heteroatoms selected from N, O and S, with remaining ring atoms being carbon, and the ring system is optionally substituted with 1, 2, 3 or 4 halogens, hydroxyl, carbonyl, nitro, cyano, amino, mercapto, —COOH, or C1-C6 alkyl;
• any one of R1, R2, R1 and R2 together or the ring systems formed by R1 and R2 together is linked to L groups;
• L is a linker and has the following structure;
• wherein or
• represents a linking site;
• D is E3 ubiquitin ligase binding ligand with the following structure,
• wherein
• represents an optionally substituted cyclic group;
• Y1, for each occurrence, is independently selected from CT1 or N;
• T1 is selected from hydrogen or deuterium;
• L is linked to W and/or D by one or more bonds.